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Stone, Edel, Katrina Campbell, Irene Grant e Olivia McAuliffe. "Understanding and Exploiting Phage–Host Interactions". Viruses 11, n.º 6 (18 de junho de 2019): 567. http://dx.doi.org/10.3390/v11060567.
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Initially described a century ago by William Twort and Felix d’Herelle, bacteriophages are bacterial viruses found ubiquitously in nature, located wherever their host cells are present. Translated literally, bacteriophage (phage) means ‘bacteria eater’. Phages interact and infect specific bacteria while not affecting other bacteria or cell lines of other organisms. Due to the specificity of these phage–host interactions, the relationship between phages and their host cells has been the topic of much research. The advances in phage biology research have led to the exploitation of these phage–host interactions and the application of phages in the agricultural and food industry. Phages may provide an alternative to the use of antibiotics, as it is well known that the emergence of antibiotic-resistant bacterial infections has become an epidemic in clinical settings. In agriculture, pre-harvest and/or post-harvest application of phages to crops may prevent the colonisation of bacteria that are detrimental to plant or human health. In addition, the abundance of data generated from genome sequencing has allowed the development of phage-derived bacterial detection systems of foodborne pathogens. This review aims to outline the specific interactions between phages and their host and how these interactions may be exploited and applied in the food industry.
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Sacher, Jessica C., Muhammad Afzal Javed, Clay S. Crippen, James Butcher, Annika Flint, Alain Stintzi e Christine M. Szymanski. "Reduced Infection Efficiency of Phage NCTC 12673 on Non-Motile Campylobacter jejuni Strains Is Related to Oxidative Stress". Viruses 13, n.º 10 (29 de setembro de 2021): 1955. http://dx.doi.org/10.3390/v13101955.
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Campylobacter jejuni is a Gram-negative foodborne pathogen that causes diarrheal disease and is associated with severe post-infectious sequelae. Bacteriophages (phages) are a possible means of reducing Campylobacter colonization in poultry to prevent downstream human infections. However, the factors influencing phage-host interactions must be better understood before this strategy can be predictably employed. Most studies have focused on Campylobacter phage binding to the host surface, with all phages classified as either capsule- or flagella-specific. Here we describe the characterization of a C. jejuni phage that requires functional flagellar glycosylation and motor genes for infection, without needing the flagella for adsorption to the cell surface. Through phage infectivity studies of targeted C. jejuni mutants, transcriptomic analysis of phage-resistant mutants, and genotypic and phenotypic analysis of a spontaneous phage variant capable of simultaneously overcoming flagellar gene dependence and sensitivity to oxidative stress, we have uncovered a link between oxidative stress, flagellar motility, and phage infectivity. Taken together, our results underscore the importance of understanding phage-host interactions beyond the cell surface and point to host oxidative stress state as an important and underappreciated consideration for future phage-host interaction studies.
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Blasche, Sonja, Stefan Wuchty, Seesandra V. Rajagopala e Peter Uetz. "The Protein Interaction Network of Bacteriophage Lambda with Its Host, Escherichia coli". Journal of Virology 87, n.º 23 (18 de setembro de 2013): 12745–55. http://dx.doi.org/10.1128/jvi.02495-13.
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Although most of the 73 open reading frames (ORFs) in bacteriophage λ have been investigated intensively, the function of many genes in host-phage interactions remains poorly understood. Using yeast two-hybrid screens of all lambda ORFs for interactions with its hostEscherichia coli, we determined a raw data set of 631 host-phage interactions resulting in a set of 62 high-confidence interactions after multiple rounds of retesting. These links suggest novel regulatory interactions between theE. colitranscriptional network and lambda proteins. Targeted host proteins and genes required for lambda infection are enriched among highly connected proteins, suggesting that bacteriophages resemble interaction patterns of human viruses. Lambda tail proteins interact with both bacterial fimbrial proteins andE. coliproteins homologous to other phage proteins. Lambda appears to dramatically differ from other phages, such as T7, because of its unusually large number of modified and processed proteins, which reduces the number of host-virus interactions detectable by yeast two-hybrid screens.
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Zhang, Mingyue, Yanan Zhou, Xinyuan Cui e Lifeng Zhu. "The Potential of Co-Evolution and Interactions of Gut Bacteria–Phages in Bamboo-Eating Pandas: Insights from Dietary Preference-Based Metagenomic Analysis". Microorganisms 12, n.º 4 (31 de março de 2024): 713. http://dx.doi.org/10.3390/microorganisms12040713.
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Bacteria and phages are two of the most abundant biological entities in the gut microbiome, and diet and host phylogeny are two of the most critical factors influencing the gut microbiome. A stable gut bacterial community plays a pivotal role in the host’s physiological development and immune health. A phage is a virus that directly infects bacteria, and phages’ close associations and interactions with bacteria are essential for maintaining the stability of the gut bacterial community and the entire microbial ecosystem. Here, we utilized 99 published metagenomic datasets from 38 mammalian species to investigate the relationship (diversity and composition) and potential interactions between gut bacterial and phage communities and the impact of diet and phylogeny on these communities. Our results highlight the co-evolutionary potential of bacterial–phage interactions within the mammalian gut. We observed a higher alpha diversity in gut bacteria than in phages and identified positive correlations between bacterial and phage compositions. Furthermore, our study revealed the significant influence of diet and phylogeny on mammalian gut bacterial and phage communities. We discovered that the impact of dietary factors on these communities was more pronounced than that of phylogenetic factors at the order level. In contrast, phylogenetic characteristics had a more substantial influence at the family level. The similar omnivorous dietary preference and closer phylogenetic relationship (family Ursidae) may contribute to the similarity of gut bacterial and phage communities between captive giant panda populations (GPCD and GPYA) and omnivorous animals (OC; including Sun bear, brown bear, and Asian black bear). This study employed co-occurrence microbial network analysis to reveal the potential interaction patterns between bacteria and phages. Compared to other mammalian groups (carnivores, herbivores, and omnivores), the gut bacterial and phage communities of bamboo-eating species (giant pandas and red pandas) exhibited a higher level of interaction. Additionally, keystone species and modular analysis showed the potential role of phages in driving and maintaining the interaction patterns between bacteria and phages in captive giant pandas. In sum, gaining a comprehensive understanding of the interaction between the gut microbiota and phages in mammals is of great significance, which is of great value in promoting healthy and sustainable mammals and may provide valuable insights into the conservation of wildlife populations, especially endangered animal species.
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Kaźmierczak, Zuzanna, Joanna Majewska, Magdalena Milczarek, Barbara Owczarek e Krystyna Dąbrowska. "Circulation of Fluorescently Labelled Phage in a Murine Model". Viruses 13, n.º 2 (14 de fevereiro de 2021): 297. http://dx.doi.org/10.3390/v13020297.
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Interactions between bacteriophages and mammals strongly affect possible applications of bacteriophages. This has created a need for tools that facilitate studies of phage circulation and deposition in tissues. Here, we propose red fluorescent protein (RFP)-labelled E. coli lytic phages as a new tool for the investigation of phage interactions with cells and tissues. The interaction of RFP-labelled phages with living eukaryotic cells (macrophages) was visualized after 20 min of co-incubation. RFP-labeled phages were applied in a murine model of phage circulation in vivo. Phages administered by three different routes (intravenously, orally, rectally) were detected through the course of time. The intravenous route of administration was the most efficient for phage delivery to multiple body compartments: 20 min after administration, virions were detected in lymph nodes, lungs, and liver; 30 min after administration, they were detectable in muscles; and 1 h after administration, phages were detected in spleen and lymph nodes. Oral and rectal administration of RFP-labelled phages allowed for their detection in the gastrointestinal (GI) tract only.
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Dicks, Leon M. T., e Wian Vermeulen. "Bacteriophage–Host Interactions and the Therapeutic Potential of Bacteriophages". Viruses 16, n.º 3 (20 de março de 2024): 478. http://dx.doi.org/10.3390/v16030478.
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Healthcare faces a major problem with the increased emergence of antimicrobial resistance due to over-prescribing antibiotics. Bacteriophages may provide a solution to the treatment of bacterial infections given their specificity. Enzymes such as endolysins, exolysins, endopeptidases, endosialidases, and depolymerases produced by phages interact with bacterial surfaces, cell wall components, and exopolysaccharides, and may even destroy biofilms. Enzymatic cleavage of the host cell envelope components exposes specific receptors required for phage adhesion. Gram-positive bacteria are susceptible to phage infiltration through their peptidoglycan, cell wall teichoic acid (WTA), lipoteichoic acids (LTAs), and flagella. In Gram-negative bacteria, lipopolysaccharides (LPSs), pili, and capsules serve as targets. Defense mechanisms used by bacteria differ and include physical barriers (e.g., capsules) or endogenous mechanisms such as clustered regularly interspaced palindromic repeat (CRISPR)-associated protein (Cas) systems. Phage proteins stimulate immune responses against specific pathogens and improve antibiotic susceptibility. This review discusses the attachment of phages to bacterial cells, the penetration of bacterial cells, the use of phages in the treatment of bacterial infections, and the limitations of phage therapy. The therapeutic potential of phage-derived proteins and the impact that genomically engineered phages may have in the treatment of infections are summarized.
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Dunne, Matthew, Mario Hupfeld, Jochen Klumpp e Martin Loessner. "Molecular Basis of Bacterial Host Interactions by Gram-Positive Targeting Bacteriophages". Viruses 10, n.º 8 (28 de julho de 2018): 397. http://dx.doi.org/10.3390/v10080397.
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The inherent ability of bacteriophages (phages) to infect specific bacterial hosts makes them ideal candidates to develop into antimicrobial agents for pathogen-specific remediation in food processing, biotechnology, and medicine (e.g., phage therapy). Conversely, phage contaminations of fermentation processes are a major concern to dairy and bioprocessing industries. The first stage of any successful phage infection is adsorption to a bacterial host cell, mediated by receptor-binding proteins (RBPs). As the first point of contact, the binding specificity of phage RBPs is the primary determinant of bacterial host range, and thus defines the remediative potential of a phage for a given bacterium. Co-evolution of RBPs and their bacterial receptors has forced endless adaptation cycles of phage-host interactions, which in turn has created a diverse array of phage adsorption mechanisms utilizing an assortment of RBPs. Over the last decade, these intricate mechanisms have been studied intensely using electron microscopy and X-ray crystallography, providing atomic-level details of this fundamental stage in the phage infection cycle. This review summarizes current knowledge surrounding the molecular basis of host interaction for various socioeconomically important Gram-positive targeting phage RBPs to their protein- and saccharide-based receptors. Special attention is paid to the abundant and best-characterized Siphoviridae family of tailed phages. Unravelling these complex phage-host dynamics is essential to harness the full potential of phage-based technologies, or for generating novel strategies to combat industrial phage contaminations.
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Tan, Demeng, Lone Gram e Mathias Middelboe. "Vibriophages and Their Interactions with the Fish Pathogen Vibrio anguillarum". Applied and Environmental Microbiology 80, n.º 10 (7 de março de 2014): 3128–40. http://dx.doi.org/10.1128/aem.03544-13.
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ABSTRACTVibrio anguillarumis an important pathogen in aquaculture, responsible for the disease vibriosis in many fish and invertebrate species. Disease control by antibiotics is a concern due to potential development and spread of antibiotic resistance. The use of bacteriophages to control the pathogen may offer a non-antibiotic-based approach to reduce vibriosis. A detailed understanding of the phage-host interaction is needed to evaluate the potential of phages to control the pathogen. In this study, we examined the diversity and interactions of 11 vibriophages, 24V. anguillarumstrains, and 13Vibriospecies strains. Together, the host ranges of the 11 phages covered all of the tested 37Vibriosp. host strains, which represented considerable temporal (20 years) and geographical (9 countries) differences in their origins of isolation. Thus, despite the occurrence of unique susceptibility patterns of the individual host isolates, key phenotypic properties related to phage susceptibility are distributed worldwide and maintained in the globalVibriocommunity for decades. The phage susceptibility pattern of the isolates did not show any relation to the physiological relationships obtained from Biolog GN2 profiles, demonstrating that similar phage susceptibility patterns occur across broad phylogenetic and physiological differences inVibriostrains. Subsequent culture experiments with two phages and twoV. anguillarumhosts demonstrated an initial strong lytic potential of the phages. However, rapid regrowth of both phage-resistant and phage-sensitive cells following the initial lysis suggested that several mechanisms of protection against phage infection had developed in the host populations.
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Deveau, Hélène, Marie-Rose Van Calsteren e Sylvain Moineau. "Effect of Exopolysaccharides on Phage-Host Interactions in Lactococcus lactis". Applied and Environmental Microbiology 68, n.º 9 (setembro de 2002): 4364–69. http://dx.doi.org/10.1128/aem.68.9.4364-4369.2002.
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ABSTRACT In this study, we report that Lactococcus lactis strains producing exopolysaccharides (EPS) are sensitive to virulent phages. Eight distinct lytic phages (Q61 to Q68) specifically infecting Eps+ strains were isolated in 47 buttermilk samples obtained from 13 North American factories. The eight phages were classified within the 936 species by the multiplex PCR method, indicating that these phages are not fundamentally distinct from those infecting Eps− L. lactis strains. The host range of these phages was determined with 19 Lactococcus strains, including 7 Eps+ and 12 Eps− cultures. Three phages (Q62, Q63, and Q64) attacked only the Eps+ strain SMQ-419, whereas the five other phages (Q61, Q65, Q66, Q67, and Q68) infected only the Eps+ strain SMQ-420. The five other Eps+ strains (H414, MLT2, MLT3, SMQ-461, and SMQ-575) as well as the 12 Eps− strains were insensitive to these phages. The monosaccharide composition of the polymer produced by the seven Eps+ strains was determined. The EPS produced by strains MLT3, SMQ-419, and SMQ-575 contained glucose, galactose, and rhamnose. The EPS fabricated by H414 contained only galactose. The EPS made by MLT2, SMQ-420, and SMQ-461 contained glucose and galactose. These findings indicate that the sugar composition of the EPS has no effect on phage sensitivity. The plasmid encoding the eps operon was cured from the two phage-sensitive strains. The cured derivatives were still phage sensitive, which indicates that EPS are not necessary for phage infection. Phage adsorption assays showed that the production of EPS does not confer a significant phage resistance phenotype.
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Loessner, Holger, Insea Schlattmeier, Marie Anders-Maurer, Isabelle Bekeredjian-Ding, Christine Rohde, Johannes Wittmann, Cornelia Pokalyuk, Oleg Krut e Christel Kamp. "Kinetic Fingerprinting Links Bacteria-Phage Interactions with Emergent Dynamics: Rapid Depletion of Klebsiella pneumoniae Indicates Phage Synergy". Antibiotics 9, n.º 7 (14 de julho de 2020): 408. http://dx.doi.org/10.3390/antibiotics9070408.
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The specific temporal evolution of bacterial and phage population sizes, in particular bacterial depletion and the emergence of a resistant bacterial population, can be seen as a kinetic fingerprint that depends on the manifold interactions of the specific phage–host pair during the course of infection. We have elaborated such a kinetic fingerprint for a human urinary tract Klebsiella pneumoniae isolate and its phage vB_KpnP_Lessing by a modeling approach based on data from in vitro co-culture. We found a faster depletion of the initially sensitive bacterial population than expected from simple mass action kinetics. A possible explanation for the rapid decline of the bacterial population is a synergistic interaction of phages which can be a favorable feature for phage therapies. In addition to this interaction characteristic, analysis of the kinetic fingerprint of this bacteria and phage combination revealed several relevant aspects of their population dynamics: A reduction of the bacterial concentration can be achieved only at high multiplicity of infection whereas bacterial extinction is hardly accomplished. Furthermore the binding affinity of the phage to bacteria is identified as one of the most crucial parameters for the reduction of the bacterial population size. Thus, kinetic fingerprinting can be used to infer phage–host interactions and to explore emergent dynamics which facilitates a rational design of phage therapies.
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WANG, WENDI. "DYNAMICS OF BACTERIA-PHAGE INTERACTIONS WITH IMMUNE RESPONSE IN A CHEMOSTAT". Journal of Biological Systems 25, n.º 04 (dezembro de 2017): 697–713. http://dx.doi.org/10.1142/s0218339017400010.
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A mathematical model of bacteria-phage interaction in the chemostat is formulated, which incorporates the host immune response with an aim to mimic phage therapy in vivo. It is shown that the host immune response induces the backward bifurcation. Thus, there exists the bistability of phage-free equilibrium with the phage-infection equilibrium. More importantly, it is found that the model exhibits the coexistence of a stable phage-infection equilibrium with a stable periodic solution. The crucial implication of these phenomena is that phage infection fails both from the smaller dose of initial injection and from the larger dose of initial injection. Thus, a proper design of phage dose is necessary for phage therapy. Further analysis indicate that the inhibition effects of bacteria and phages can induce periodic oscillations and modulated oscillation.
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Romero, Dennis A., Damian Magill, Anne Millen, Philippe Horvath e Christophe Fremaux. "Dairy lactococcal and streptococcal phage–host interactions: an industrial perspective in an evolving phage landscape". FEMS Microbiology Reviews 44, n.º 6 (5 de outubro de 2020): 909–32. http://dx.doi.org/10.1093/femsre/fuaa048.
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ABSTRACT Almost a century has elapsed since the discovery of bacteriophages (phages), and 85 years have passed since the emergence of evidence that phages can infect starter cultures, thereby impacting dairy fermentations. Soon afterward, research efforts were undertaken to investigate phage interactions regarding starter strains. Investigations into phage biology and morphology and phage–host relationships have been aimed at mitigating the negative impact phages have on the fermented dairy industry. From the viewpoint of a supplier of dairy starter cultures, this review examines the composition of an industrial phage collection, providing insight into the development of starter strains and cultures and the evolution of phages in the industry. Research advances in the diversity of phages and structural bases for phage–host recognition and an overview of the perpetual arms race between phage virulence and host defense are presented, with a perspective toward the development of improved phage-resistant starter culture systems.
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Kraus, Samuel, Megan L. Fletcher, Urszula Łapińska, Krina Chawla, Evan Baker, Erin L. Attrill, Paul O’Neill et al. "Phage-induced efflux down-regulation boosts antibiotic efficacy". PLOS Pathogens 20, n.º 6 (28 de junho de 2024): e1012361. http://dx.doi.org/10.1371/journal.ppat.1012361.
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The interactions between a virus and its host vary in space and time and are affected by the presence of molecules that alter the physiology of either the host or the virus. Determining the molecular mechanisms at the basis of these interactions is paramount for predicting the fate of bacterial and phage populations and for designing rational phage-antibiotic therapies. We study the interactions between stationary phase Burkholderia thailandensis and the phage ΦBp-AMP1. Although heterogeneous genetic resistance to phage rapidly emerges in B. thailandensis, the presence of phage enhances the efficacy of three major antibiotic classes, the quinolones, the beta-lactams and the tetracyclines, but antagonizes tetrahydrofolate synthesis inhibitors. We discovered that enhanced antibiotic efficacy is facilitated by reduced antibiotic efflux in the presence of phage. This new phage-antibiotic therapy allows for eradication of stationary phase bacteria, whilst requiring reduced antibiotic concentrations, which is crucial for treating infections in sites where it is difficult to achieve high antibiotic concentrations.
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Stachurska, Xymena, Krzysztof Cendrowski, Kamila Pachnowska, Agnieszka Piegat, Ewa Mijowska e Paweł Nawrotek. "Nanoparticles Influence Lytic Phage T4-like Performance In Vitro". International Journal of Molecular Sciences 23, n.º 13 (28 de junho de 2022): 7179. http://dx.doi.org/10.3390/ijms23137179.
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Little is known about interactions of non-filamentous, complex-structured lytic phages and free, non-ordered nanoparticles. Emerging questions about their possible bio-sanitization co-applications or predictions of possible contact effects in the environment require testing. Therefore, we revealed the influence of various nanoparticles (NPs; SiO2, TiO2-SiO2, TiO2, Fe3O4, Fe3O4-SiO2 and SiO2-Fe3O4-TiO2) on a T4-like phage. In great detail, we investigated phage plaque-forming ability, phage lytic performance, phage progeny burst times and titers by the eclipse phase determinations. Additionally, it was proved that TEM micrographs and results of NP zeta potentials (ZP) were crucial to explain the obtained microbiological data. We propose that the mere presence of the nanoparticle charge is not sufficient for the phage to attach specifically to the NPs, consequently influencing the phage performance. The zeta potential values in the NPs are of the greatest influence. The threshold values were established at ZP < −35 (mV) for phage tail binding, and ZP > 35 (mV) for phage head binding. When NPs do not meet these requirements, phage–nanoparticle physical interaction becomes nonspecific. We also showed that NPs altered the phage lytic activity, regardless of the used NP concentration. Most of the tested nanoparticles positively influenced the phage lytic performance, except for SiO2 and Fe3O4-SiO2, with a ZP lower than −35 (mV), binding with the phage infective part—the tail.
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Tan, Demeng, Yiyuan Zhang, Mengjun Cheng, Shuai Le, Jingmin Gu, Juan Bao, Jinhong Qin, Xiaokui Guo e Tongyu Zhu. "Characterization of Klebsiella pneumoniae ST11 Isolates and Their Interactions with Lytic Phages". Viruses 11, n.º 11 (19 de novembro de 2019): 1080. http://dx.doi.org/10.3390/v11111080.
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The bacterial pathogen Klebsiella pneumoniae causes urinary tract infections in immunocompromised patients. Generally, the overuse of antibiotics contributes to the potential development and the spread of antibiotic resistance. In fact, certain strains of K. pneumoniae are becoming increasingly resistant to antibiotics, making infection by these strains more difficult to treat. The use of bacteriophages to control pathogens may offer a non-antibiotic-based approach to treat multidrug-resistant (MDR) infections. However, a detailed understanding of phage–host interactions is crucial in order to explore the potential success of phage-therapy for treatment. In this study, we investigated the molecular epidemiology of nine carbapenemase-producing K. pneumoniae isolates from a local hospital in Shanghai, China. All strain isolates belong to sequence type 11 (ST11) and harbor the blaKPC-2 gene. The S1-PFGE (S1 nuclease pulsed field gel electrophoresis) pattern of the isolates did not show any relationship to the multilocus sequence typing (MLST) profiles. In addition, we characterized phage 117 and phage 31 and assessed the potential application of phage therapy in treating K. pneumoniae infections in vitro. The results of morphological and genomic analyses suggested that both phages are affiliated to the T7 virus genus of the Podoviridae family. We also explored phage–host interactions during growth in both planktonic cells and biofilms. The phages’ heterogeneous lytic capacities against K. pneumoniae strains were demonstrated experimentally. Subsequent culture and urine experiments with phage 117 and host Kp36 initially demonstrated a strong lytic activity of the phages. However, rapid regrowth was observed following the initial lysis which suggests that phage resistant mutants were selected in the host populations. Additionally, a phage cocktail (117 + 31) was prepared and investigated for antimicrobial activity. In Luria Broth (LB) cultures, we observed that the cocktail showed significantly higher antimicrobial activity than phage 117 alone, but this was not observed in urine samples. Together, the results demonstrate the potential therapeutic value of phages in treating K. pneumoniae urinary tract infections.
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Duplessis, Martin, Céline M. Lévesque e Sylvain Moineau. "Characterization of Streptococcus thermophilus Host Range Phage Mutants". Applied and Environmental Microbiology 72, n.º 4 (abril de 2006): 3036–41. http://dx.doi.org/10.1128/aem.72.4.3036-3041.2006.
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ABSTRACT To investigate phage-host interactions in Streptococcus thermophilus, a phage-resistant derivative (SMQ-301R) was obtained by challenging a Tn917 library of phage-sensitive strain S. thermophilus SMQ-301 with virulent phage DT1. Mutants of phages DT1 and MD2 capable of infecting SMQ-301 and SMQ-301R were isolated at a frequency of 10−6. Four host range phage mutants were analyzed further and compared to the two wild-type phages. Altogether, three genes (orf15, orf17, and orf18) contained point mutations leading to amino acid substitutions and were responsible for the expanded host range. These three proteins were also identified in both phages by N-terminal sequencing and/or matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. The results suggest that at least three phage structural proteins may be involved in phage-host interactions in S. thermophilus.
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Marsh, P., e E. M. H. Wellington. "Phage-host interactions in soil". FEMS Microbiology Ecology 15, n.º 1-2 (novembro de 1994): 99–107. http://dx.doi.org/10.1111/j.1574-6941.1994.tb00234.x.
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Cenens, William, Angella Makumi, Mehari Tesfazgi Mebrhatu, Rob Lavigne e Abram Aertsen. "Phage–host interactions during pseudolysogeny". Bacteriophage 3, n.º 1 (janeiro de 2013): e25029. http://dx.doi.org/10.4161/bact.25029.
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Tan, Demeng, Amalie Dahl e Mathias Middelboe. "Vibriophages Differentially Influence Biofilm Formation by Vibrio anguillarum Strains". Applied and Environmental Microbiology 81, n.º 13 (24 de abril de 2015): 4489–97. http://dx.doi.org/10.1128/aem.00518-15.
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ABSTRACTVibrio anguillarumis an important pathogen in marine aquaculture, responsible for vibriosis. Bacteriophages can potentially be used to control bacterial pathogens; however, successful application of phages requires a detailed understanding of phage-host interactions under both free-living and surface-associated growth conditions. In this study, we exploredin vitrophage-host interactions in two different strains ofV. anguillarum(BA35 and PF430-3) during growth in microcolonies, biofilms, and free-living cells. Two vibriophages, ΦH20 (Siphoviridae) and KVP40 (Myoviridae), had completely different effects on the biofilm development. Addition of phage ΦH20 to strain BA35 showed efficient control of biofilm formation and density of free-living cells. The interactions between BA35 and ΦH20 were thus characterized by a strong phage control of the phage-sensitive population and subsequent selection for phage-resistant mutants. Addition of phage KVP40 to strain PF430-3 resulted in increased biofilm development, especially during the early stage. Subsequent experiments in liquid cultures showed that addition of phage KVP40 stimulated the aggregation of host cells, which protected the cells against phage infection. By the formation of biofilms, strain PF430-3 created spatial refuges that protected the host from phage infection and allowed coexistence between phage-sensitive cells and lytic phage KVP40. Together, the results demonstrate highly variable phage protection mechanisms in two closely relatedV. anguillarumstrains, thus emphasizing the challenges of using phages to control vibriosis in aquaculture and adding to the complex roles of phages as drivers of prokaryotic diversity and population dynamics.
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Li, Na, Yigang Zeng, Bijie Hu, Tongyu Zhu, Sine Lo Svenningsen, Mathias Middelboe e Demeng Tan. "Interactions between the Prophage 919TP and Its Vibrio cholerae Host: Implications of gmd Mutation for Phage Resistance, Cell Auto-Aggregation, and Motility". Viruses 13, n.º 12 (23 de novembro de 2021): 2342. http://dx.doi.org/10.3390/v13122342.
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Prophage 919TP is widely distributed among Vibrio cholera and is induced to produce free φ919TP phage particles. However, the interactions between prophage φ919TP, the induced phage particle, and its host remain unknown. In particular, phage resistance mechanisms and potential fitness trade-offs, resulting from phage resistance, are unresolved. In this study, we examined a prophage 919TP-deleted variant of V. cholerae and its interaction with a modified lytic variant of the induced prophage (φ919TP cI-). Specifically, the phage-resistant mutant was isolated by challenging a prophage-deleted variant with lytic phage φ919TP cI-. Further, the comparative genomic analysis of wild-type and φ919TP cI--resistant mutant predicted that phage φ919TP cI- selects for phage-resistant mutants harboring a mutation in key steps of lipopolysaccharide (LPS) O-antigen biosynthesis, causing a single-base-pair deletion in gene gmd. Our study showed that the gmd-mediated O-antigen defect can cause pleiotropic phenotypes, e.g., cell autoaggregation and reduced swarming motility, emphasizing the role of phage-driven diversification in V. cholerae. The developed approach assists in the identification of genetic determinants of host specificity and is used to explore the molecular mechanism underlying phage-host interactions. Our findings contribute to the understanding of prophage-facilitated horizontal gene transfer and emphasize the potential for developing new strategies to optimize the use of phages in bacterial pathogen control.
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Zhang, Bingyan, Jiayi Xu, Xiaoqi He, Yigang Tong e Huiying Ren. "Interactions between Jumbo Phage SA1 and Staphylococcus: A Global Transcriptomic Analysis". Microorganisms 10, n.º 8 (7 de agosto de 2022): 1590. http://dx.doi.org/10.3390/microorganisms10081590.
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Staphylococcus aureus (S. aureus) is an important zoonotic pathogen that poses a serious health concern to humans and cattle worldwide. Although it has been proven that lytic phages may successfully kill S. aureus, the interaction between the host and the phage has yet to be thoroughly investigated, which will likely limit the clinical application of phage. Here, RNA sequencing (RNA-seq) was used to examine the transcriptomics of jumbo phage SA1 and Staphylococcus JTB1-3 during a high multiplicity of infection (MOI) and RT-qPCR was used to confirm the results. The RNA-seq analysis revealed that phage SA1 took over the transcriptional resources of the host cells and that the genes were categorized as early, middle, and late, based on the expression levels during infection. A minor portion of the resources of the host was employed to enable phage replication after infection because only 35.73% (997/2790) of the host genes were identified as differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the phage infection mainly affected the nucleotide metabolism, protein metabolism, and energy-related metabolism of the host. Moreover, the expression of the host genes involved in anti-phage systems, virulence, and drug resistance significantly changed during infection. This research gives a fresh understanding of the relationship between jumbo phages and their Gram-positive bacteria hosts and provides a reference for studying phage treatment and antibiotics.
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Clokie, Martha, e Thomas Sicheritz-Ponte´n. "Lungs, Liposomes, Libraries, and Likely Interactions Between Phages and Eukaryotic Cells". PHAGE 4, n.º 1 (1 de março de 2023): 1–2. http://dx.doi.org/10.1089/phage.2023.29041.editorial.
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Mi, Yanze, Yile He, Jinhui Mi, Yunfei Huang, Huahao Fan, Lihua Song, Xiaoping An, Shan Xu, Mengzhe Li e Yigang Tong. "Genetic and Phenotypic Analysis of Phage-Resistant Mutant Fitness Triggered by Phage–Host Interactions". International Journal of Molecular Sciences 24, n.º 21 (26 de outubro de 2023): 15594. http://dx.doi.org/10.3390/ijms242115594.
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The emergence of phage-resistant bacterial strains is one of the biggest challenges for phage therapy. However, the emerging phage-resistant bacteria are often accompanied by adaptive trade-offs, which supports a therapeutic strategy called “phage steering”. The key to phage steering is to guide the bacterial population toward an evolutionary direction that is favorable for treatment. Thus, it is important to systematically investigate the impacts of phages targeting different bacterial receptors on the fitness of the bacterial population. Herein, we employed 20 different phages to impose strong evolutionary pressure on the host Pseudomonas aeruginosa PAO1 and examined the genetic and phenotypic responses of their phage-resistant mutants. Among these strains with impaired adsorptions, four types of mutations associated with bacterial receptors were identified, namely, lipopolysaccharides (LPSs), type IV pili (T4Ps), outer membrane proteins (OMPs), and exopolysaccharides (EPSs). PAO1, responding to LPS- and EPS-dependent phage infections, mostly showed significant growth impairment and virulence attenuation. Most mutants with T4P-related mutations exhibited a significant decrease in motility and biofilm formation ability, while the mutants with OMP-related mutations required the lowest fitness cost out of the bacterial populations. Apart from fitness costs, PAO1 strains might lose their resistance to antibiotics when counteracting with phages, such as the presence of large-fragment mutants in this study, which may inspire the usage of phage–antibiotic combination strategies. This work provides methods that leverage the merits of phage resistance relative to obtaining therapeutically beneficial outcomes with respect to phage-steering strategies.
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Esteves, Nathaniel C., Danielle N. Bigham e Birgit E. Scharf. "Phages on filaments: A genetic screen elucidates the complex interactions between Salmonella enterica flagellin and bacteriophage Chi". PLOS Pathogens 19, n.º 8 (3 de agosto de 2023): e1011537. http://dx.doi.org/10.1371/journal.ppat.1011537.
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The bacterial flagellum is a rotary motor organelle and important virulence factor that propels motile pathogenic bacteria, such as Salmonella enterica, through their surroundings. Bacteriophages, or phages, are viruses that solely infect bacteria. As such, phages have myriad applications in the healthcare field, including phage therapy against antibiotic-resistant bacterial pathogens. Bacteriophage χ (Chi) is a flagellum-dependent (flagellotropic) bacteriophage, which begins its infection cycle by attaching its long tail fiber to the S. enterica flagellar filament as its primary receptor. The interactions between phage and flagellum are poorly understood, as are the reasons that χ only kills certain Salmonella serotypes while others entirely evade phage infection. In this study, we used molecular cloning, targeted mutagenesis, heterologous flagellin expression, and phage-host interaction assays to determine which domains within the flagellar filament protein flagellin mediate this complex interaction. We identified the antigenic N- and C-terminal D2 domains as essential for phage χ binding, with the hypervariable central D3 domain playing a less crucial role. Here, we report that the primary structure of the Salmonella flagellin D2 domains is the major determinant of χ adhesion. The phage susceptibility of a strain is directly tied to these domains. We additionally uncovered important information about flagellar function. The central and most variable domain, D3, is not required for motility in S. Typhimurium 14028s, as it can be deleted or its sequence composition can be significantly altered with minimal impacts on motility. Further knowledge about the complex interactions between flagellotropic phage χ and its primary bacterial receptor may allow genetic engineering of its host range for use as targeted antimicrobial therapy against motile pathogens of the χ-host genera Salmonella, Escherichia, or Serratia.
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Attai, Hedieh, e Pamela J. B. Brown. "Isolation and Characterization T4- and T7-Like Phages that Infect the Bacterial Plant Pathogen Agrobacterium tumefaciens". Viruses 11, n.º 6 (7 de junho de 2019): 528. http://dx.doi.org/10.3390/v11060528.
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In the rhizosphere, bacteria–phage interactions are likely to have important impacts on the ecology of microbial communities and microbe–plant interactions. To better understand the dynamics of Agrobacteria–phage interactions, we have isolated diverse bacteriophages which infect the bacterial plant pathogen, Agrobacterium tumefaciens. Here, we complete the genomic characterization of Agrobacterium tumefaciens phages Atu_ph04 and Atu_ph08. Atu_ph04—a T4-like phage belonging to the Myoviridae family—was isolated from waste water and has a 143,349 bp genome that encodes 223 predicted open reading frames (ORFs). Based on phylogenetic analysis and whole-genome alignments, Atu_ph04 is a member of a newly described T4 superfamily that contains other Rhizobiales-infecting phages. Atu_ph08, a member of the Podoviridae T7-like family, was isolated from waste water, has a 59,034 bp genome, and encodes 75 ORFs. Based on phylogenetic analysis and whole-genome alignments, Atu_ph08 may form a new T7 superfamily which includes Sinorhizobium phage PCB5 and Ochrobactrum phage POI1126. Atu_ph08 is predicted to have lysogenic activity, as we found evidence of an integrase and several transcriptional repressors with similarity to proteins in transducing phage P22. Together, this data suggests that Agrobacterium phages are diverse in morphology, genomic content, and lifestyle.
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Maffei, Enea, Aisylu Shaidullina, Marco Burkolter, Yannik Heyer, Fabienne Estermann, Valentin Druelle, Patrick Sauer et al. "Systematic exploration of Escherichia coli phage–host interactions with the BASEL phage collection". PLOS Biology 19, n.º 11 (16 de novembro de 2021): e3001424. http://dx.doi.org/10.1371/journal.pbio.3001424.
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Bacteriophages, the viruses infecting bacteria, hold great potential for the treatment of multidrug-resistant bacterial infections and other applications due to their unparalleled diversity and recent breakthroughs in their genetic engineering. However, fundamental knowledge of the molecular mechanisms underlying phage–host interactions is mostly confined to a few traditional model systems and did not keep pace with the recent massive expansion of the field. The true potential of molecular biology encoded by these viruses has therefore remained largely untapped, and phages for therapy or other applications are often still selected empirically. We therefore sought to promote a systematic exploration of phage–host interactions by composing a well-assorted library of 68 newly isolated phages infecting the model organism Escherichia coli that we share with the community as the BASEL (BActeriophage SElection for your Laboratory) collection. This collection is largely representative of natural E. coli phage diversity and was intensively characterized phenotypically and genomically alongside 10 well-studied traditional model phages. We experimentally determined essential host receptors of all phages, quantified their sensitivity to 11 defense systems across different layers of bacterial immunity, and matched these results to the phages’ host range across a panel of pathogenic enterobacterial strains. Clear patterns in the distribution of phage phenotypes and genomic features highlighted systematic differences in the potency of different immunity systems and suggested the molecular basis of receptor specificity in several phage groups. Our results also indicate strong trade-offs between fitness traits like broad host recognition and resistance to bacterial immunity that might drive the divergent adaptation of different phage groups to specific ecological niches. We envision that the BASEL collection will inspire future work exploring the biology of bacteriophages and their hosts by facilitating the discovery of underlying molecular mechanisms as the basis for an effective translation into biotechnology or therapeutic applications.
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Karlsson, Fredrik, Carl A. K. Borrebaeck, Nina Nilsson e Ann-Christin Malmborg-Hager. "The Mechanism of Bacterial Infection by Filamentous Phages Involves Molecular Interactions between TolA and Phage Protein 3 Domains". Journal of Bacteriology 185, n.º 8 (15 de abril de 2003): 2628–34. http://dx.doi.org/10.1128/jb.185.8.2628-2634.2003.
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ABSTRACT The early events in filamentous bacteriophage infection of gram-negative bacteria are mediated by the gene 3 protein (g3p) of the virus. This protein has a sophisticated domain organization consisting of two N-terminal domains and one C-terminal domain, separated by flexible linkers. The molecular interactions between these domains and the known bacterial coreceptor protein (TolA) were studied using a biosensor technique, and we report here on interactions of the viral coat protein with TolA, as well as on interactions between the TolA molecules. We detected an interaction between the pilus binding second domain (N2) of protein 3 and the bacterial TolA. This novel interaction was found to depend on the periplasmatic domain of TolA (TolAII). Furthermore, extensive interaction was detected between TolA molecules, demonstrating that bacterial TolA has the ability to interact functionally with itself during phage infection. The kinetics of g3p binding to TolA is also different from that of bacteriocins, since both N-terminal domains of g3p were found to interact with TolA. The multiple roles for each of the separate g3p and TolA domains imply a delicate interaction network during the phage infection process and a model for the infection mechanism is hypothesized.
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Mäntynen, Sari, Elina Laanto, Hanna M. Oksanen, Minna M. Poranen e Samuel L. Díaz-Muñoz. "Black box of phage–bacterium interactions: exploring alternative phage infection strategies". Open Biology 11, n.º 9 (setembro de 2021): 210188. http://dx.doi.org/10.1098/rsob.210188.
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The canonical lytic–lysogenic binary has been challenged in recent years, as more evidence has emerged on alternative bacteriophage infection strategies. These infection modes are little studied, and yet they appear to be more abundant and ubiquitous in nature than previously recognized, and can play a significant role in the ecology and evolution of their bacterial hosts. In this review, we discuss the extent, causes and consequences of alternative phage lifestyles, and clarify conceptual and terminological confusion to facilitate research progress. We propose distinct definitions for the terms ‘pseudolysogeny’ and ‘productive or non-productive chronic infection’, and distinguish them from the carrier state life cycle, which describes a population-level phenomenon. Our review also finds that phages may change their infection modes in response to environmental conditions or the physiological state of the host cell. We outline known molecular mechanisms underlying the alternative phage–host interactions, including specific genetic pathways and their considerable biotechnological potential. Moreover, we discuss potential implications of the alternative phage lifestyles for microbial biology and ecosystem functioning, as well as applied topics such as phage therapy.
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Schiettekatte, Olivier, Elsa Beurrier, Luisa De Sordi e Anne Chevallereau. "“French Phage Network” Annual Conference—Seventh Meeting Report". Viruses 15, n.º 2 (10 de fevereiro de 2023): 495. http://dx.doi.org/10.3390/v15020495.
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The French Phage Network (Phages.fr) has continuously grown since its foundation, eight years ago. The annual conference, held at the Institut Pasteur in Paris, attracted 164 participants from the 11th to the 13th of October 2022. Researchers from academic laboratories, hospitals and private companies shared their ongoing projects and breakthroughs in the very institute where Felix d’Hérelle developed phage therapy over a century ago. The conference was divided into four thematic sessions, each opened by a keynote lecture: “Interaction between phages, mobile genetic elements and bacterial immune system,” “Ecology and evolution of phage–bacteria interactions,” “Molecular interplay between phages and their hosts” and “Therapeutic and biotechnological applications of phages.” A total of 32 talks and 33 posters were presented during the conference.
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Taslem Mourosi, Jarin, Ayobami Awe, Wenzheng Guo, Himanshu Batra, Harrish Ganesh, Xiaorong Wu e Jingen Zhu. "Understanding Bacteriophage Tail Fiber Interaction with Host Surface Receptor: The Key “Blueprint” for Reprogramming Phage Host Range". International Journal of Molecular Sciences 23, n.º 20 (12 de outubro de 2022): 12146. http://dx.doi.org/10.3390/ijms232012146.
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Bacteriophages (phages), as natural antibacterial agents, are being rediscovered because of the growing threat of multi- and pan-drug-resistant bacterial pathogens globally. However, with an estimated 1031 phages on the planet, finding the right phage to recognize a specific bacterial host is like looking for a needle in a trillion haystacks. The host range of a phage is primarily determined by phage tail fibers (or spikes), which initially mediate reversible and specific recognition and adsorption by susceptible bacteria. Recent significant advances at single-molecule and atomic levels have begun to unravel the structural organization of tail fibers and underlying mechanisms of phage–host interactions. Here, we discuss the molecular mechanisms and models of the tail fibers of the well-characterized T4 phage’s interaction with host surface receptors. Structure–function knowledge of tail fibers will pave the way for reprogramming phage host range and will bring future benefits through more-effective phage therapy in medicine. Furthermore, the design strategies of tail fiber engineering are briefly summarized, including machine-learning-assisted engineering inspired by the increasingly enormous amount of phage genetic information.
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Beggs, Grace A., e Bonnie L. Bassler. "Phage small proteins play large roles in phage–bacterial interactions". Current Opinion in Microbiology 80 (agosto de 2024): 102519. http://dx.doi.org/10.1016/j.mib.2024.102519.
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Cairns, Johannes, Sebastián Coloma, Kaarina Sivonen e Teppo Hiltunen. "Evolving interactions between diazotrophic cyanobacterium and phage mediate nitrogen release and host competitive ability". Royal Society Open Science 3, n.º 12 (dezembro de 2016): 160839. http://dx.doi.org/10.1098/rsos.160839.
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Interactions between nitrogen-fixing (i.e. diazotrophic) cyanobacteria and their viruses, cyanophages, can have large-scale ecosystem effects. These effects are mediated by temporal alterations in nutrient availability in aquatic systems owing to the release of nitrogen and carbon sources from cells lysed by phages, as well as by ecologically important changes in the diversity and fitness of cyanobacterial populations that evolve in the presence of phages. However, ecological and evolutionary feedbacks between phages and nitrogen-fixing cyanobacteria are still relative poorly understood. Here, we used an experimental evolution approach to test the effect of interactions between a common filamentous, nitrogen-fixing cyanobacterium ( Nodularia sp.) and its phage on cellular nitrogen release and host properties. Ecological, community-level effects of phage-mediated nitrogen release were tested with a phytoplankton bioassay. We found that cyanobacterial nitrogen release increased significantly as a result of viral lysis, which was associated with enhanced growth of phytoplankton species in cell-free filtrates compared with phage-resistant host controls in which lysis and subsequent nutrient release did not occur after phage exposure. We also observed an ecologically important change among phage-evolved cyanobacteria with phage-resistant phenotypes, a short-filamentous morphotype with reduced buoyancy compared with the ancestral long-filamentous morphotype. Reduced buoyancy might decrease the ability of these morphotypes to compete for light compared with longer, more buoyant filaments. Together, these findings demonstrate the potential of cyanobacteria–phage interactions to affect ecosystem biogeochemical cycles and planktonic community dynamics.
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Nilsson, Emelie, Oliver W. Bayfield, Daniel Lundin, Alfred A. Antson e Karin Holmfeldt. "Diversity and Host Interactions among Virulent and Temperate Baltic Sea Flavobacterium Phages". Viruses 12, n.º 2 (30 de janeiro de 2020): 158. http://dx.doi.org/10.3390/v12020158.
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Viruses in aquatic environments play a key role in microbial population dynamics and nutrient cycling. In particular, bacteria of the phylum Bacteriodetes are known to participate in recycling algal blooms. Studies of phage–host interactions involving this phylum are hence important to understand the processes shaping bacterial and viral communities in the ocean as well as nutrient cycling. In this study, we isolated and sequenced three strains of flavobacteria—LMO6, LMO9, LMO8—and 38 virulent phages infecting them. These phages represent 15 species, occupying three novel genera. Additionally, one temperate phage was induced from LMO6 and was found to be competent at infecting LMO9. Functions could be predicted for a limited number of phage genes, mainly representing roles in DNA replication and virus particle formation. No metabolic genes were detected. While the phages isolated on LMO8 could infect all three bacterial strains, the LMO6 and LMO9 phages could not infect LMO8. Of the phages isolated on LMO9, several showed a host-derived reduced efficiency of plating on LMO6, potentially due to differences in DNA methyltransferase genes. Overall, these phage–host systems contribute novel genetic information to our sequence databases and present valuable tools for the study of both virulent and temperate phages.
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Mohammed, Manal, e Beata Orzechowska. "Characterisation of Phage Susceptibility Variation in Salmonellaenterica Serovar Typhimurium DT104 and DT104b". Microorganisms 9, n.º 4 (17 de abril de 2021): 865. http://dx.doi.org/10.3390/microorganisms9040865.
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The surge in mortality and morbidity rates caused by multidrug-resistant (MDR) bacteria prompted a renewal of interest in bacteriophages (phages) as clinical therapeutics and natural biocontrol agents. Nevertheless, bacteria and phages are continually under the pressure of the evolutionary phage–host arms race for survival, which is mediated by co-evolving resistance mechanisms. In Anderson phage typing scheme of Salmonella Typhimurium, the epidemiologically related definitive phage types, DT104 and DT104b, display significantly different phage susceptibility profiles. This study aimed to characterise phage resistance mechanisms and genomic differences that may be responsible for the divergent phage reaction patterns in S. Typhimurium DT104 and DT104b using whole genome sequencing (WGS). The analysis of intact prophages, restriction–modification systems (RMS), plasmids and clustered regularly interspaced short palindromic repeats (CRISPRs), as well as CRISPR-associated proteins, revealed no unique genetic determinants that might explain the variation in phage susceptibility among the two phage types. Moreover, analysis of genes coding for potential phage receptors revealed no differences among DT104 and DT104b strains. However, the findings propose the need for experimental assessment of phage-specific receptors on the bacterial cell surface and analysis of bacterial transcriptome using RNA sequencing which will explain the differences in bacterial susceptibility to phages. Using Anderson phage typing scheme of Salmonella Typhimurium for the study of bacteria-phage interaction will help improving our understanding of host–phage interactions which will ultimately lead to the development of phage-based technologies, enabling effective infection control.
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Carroll-Portillo, Amanda, e Henry C. Lin. "Exploring Mucin as Adjunct to Phage Therapy". Microorganisms 9, n.º 3 (28 de fevereiro de 2021): 509. http://dx.doi.org/10.3390/microorganisms9030509.
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Conventional phage therapy using bacteriophages (phages) for specific targeting of pathogenic bacteria is not always useful as a therapeutic for gastrointestinal (GI) dysfunction. Complex dysbiotic GI disorders such as small intestinal bowel overgrowth (SIBO), ulcerative colitis (UC), or Crohn’s disease (CD) are even more difficult to treat as these conditions have shifts in multiple populations of bacteria within the microbiome. Such community-level structural changes in the gut microbiota may require an alternative to conventional phage therapy such as fecal virome transfer or a phage cocktail capable of targeting multiple bacterial species. Additionally, manipulation of the GI microenvironment may enhance beneficial bacteria–phage interactions during treatment. Mucin, produced along the entire length of the GI tract to protect the underlying mucosa, is a prominent contributor to the GI microenvironment and may facilitate bacteria–phage interactions in multiple ways, potentially serving as an adjunct during phage therapy. In this review, we will describe what is known about the role of mucin within the GI tract and how its facilitation of bacteria–phage interactions should be considered in any effort directed at optimizing effectiveness of a phage therapy for gastrointestinal dysbiosis.
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Flores, C. O., J. R. Meyer, S. Valverde, L. Farr e J. S. Weitz. "Statistical structure of host-phage interactions". Proceedings of the National Academy of Sciences 108, n.º 28 (27 de junho de 2011): E288—E297. http://dx.doi.org/10.1073/pnas.1101595108.
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Guerrero-Ferreira, R., e E. Wright. "Structural Analysis of Proteobacteria-Phage Interactions". Microscopy and Microanalysis 16, S2 (julho de 2010): 1066–67. http://dx.doi.org/10.1017/s143192761006160x.
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DeWitt, Natalie. "Mapping protein interactions by phage display". Nature Biotechnology 17, n.º 12 (dezembro de 1999): 1150. http://dx.doi.org/10.1038/70682.
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de Sousa, Jorge A. M., Amandine Buffet, Matthieu Haudiquet, Eduardo P. C. Rocha e Olaya Rendueles. "Modular prophage interactions driven by capsule serotype select for capsule loss under phage predation". ISME Journal 14, n.º 12 (30 de julho de 2020): 2980–96. http://dx.doi.org/10.1038/s41396-020-0726-z.
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Abstract Klebsiella species are able to colonize a wide range of environments and include worrisome nosocomial pathogens. Here, we sought to determine the abundance and infectivity of prophages of Klebsiella to understand how the interactions between induced prophages and bacteria affect population dynamics and evolution. We identified many prophages in the species, placing these taxa among the top 5% of the most polylysogenic bacteria. We selected 35 representative strains of the Klebsiella pneumoniae species complex to establish a network of induced phage–bacteria interactions. This revealed that many prophages are able to enter the lytic cycle, and subsequently kill or lysogenize closely related Klebsiella strains. Although 60% of the tested strains could produce phages that infect at least one other strain, the interaction network of all pairwise cross-infections is very sparse and mostly organized in modules corresponding to the strains’ capsule serotypes. Accordingly, capsule mutants remain uninfected showing that the capsule is a key factor for successful infections. Surprisingly, experiments in which bacteria are predated by their own prophages result in accelerated loss of the capsule. Our results show that phage infectiousness defines interaction modules between small subsets of phages and bacteria in function of capsule serotype. This limits the role of prophages as competitive weapons because they can infect very few strains of the species complex. This should also restrict phage-driven gene flow across the species. Finally, the accelerated loss of the capsule in bacteria being predated by their own phages, suggests that phages drive serotype switch in nature.
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Koonjan, Shazeeda, Carlos Cardoso Palacios e Anders S. Nilsson. "Population Dynamics of a Two Phages–One Host Infection System Using Escherichia coli Strain ECOR57 and Phages vB_EcoP_SU10 and vB_EcoD_SU57". Pharmaceuticals 15, n.º 3 (22 de fevereiro de 2022): 268. http://dx.doi.org/10.3390/ph15030268.
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In this study, we looked at the population dynamics of a two phages-one host system using phages vB_EcoP_SU10 (SU10) and vB_EcoD_SU57 (SU57) and the bacteria Escherichia coli, strain ECOR57. Phage-specific growth curves were observed where infections by SU10 resulted in a moderate production of phages and infections by SU57 resulted in a fast and extensive production of phage progeny. Sequentially adding SU10 followed by SU57 did not produce a significant change in growth rates, whereas adding SU57 followed by SU10 resulted in a decrease in SU10 titer The efficiency of the plating assays showed that ECOR57 exhibited a resistance spectrum after infection by both the single and combined phages. Phage-resistant bacteria exhibited four different morphotypes (i.e., normal, slimy, edgy, and pointy). The normal and edgy morphotypes had a high frequency of developing resistance. Bacterial growth and biofilm assays indicated that the edgy and pointy morphotypes reached a stationary phase faster and produced more biofilm compared to the wild type. These findings suggest that the dynamic structure of phage–bacteria communities dictate resistance evolution and development. Understanding when and how resistances arise and phage(s)–hosts interactions could aid in the design of phage therapy treatments.
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Zborowsky, Sophia, e Debbie Lindell. "Resistance in marine cyanobacteria differs against specialist and generalist cyanophages". Proceedings of the National Academy of Sciences 116, n.º 34 (5 de agosto de 2019): 16899–908. http://dx.doi.org/10.1073/pnas.1906897116.
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Long-term coexistence between unicellular cyanobacteria and their lytic viruses (cyanophages) in the oceans is thought to be due to the presence of sensitive cells in which cyanophages reproduce, ultimately killing the cell, while other cyanobacteria survive due to resistance to infection. Here, we investigated resistance in marine cyanobacteria from the genera Synechococcus and Prochlorococcus and compared modes of resistance against specialist and generalist cyanophages belonging to the T7-like and T4-like cyanophage families. Resistance was extracellular in most interactions against specialist cyanophages irrespective of the phage family, preventing entry into the cell. In contrast, resistance was intracellular in practically all interactions against generalist T4-like cyanophages. The stage of intracellular arrest was interaction-specific, halting at various stages of the infection cycle. Incomplete infection cycles proceeded to various degrees of phage genome transcription and translation as well as phage genome replication in numerous interactions. In a particularly intriguing case, intracellular capsid assembly was observed, but the phage genome was not packaged. The cyanobacteria survived the encounter despite late-stage infection and partial genome degradation. We hypothesize that this is tolerated due to genome polyploidy, which we found for certain strains of both Synechococcus and Prochlorococcus. Our findings unveil a heavy cost of promiscuous entry of generalist phages into nonhost cells that is rarely paid by specialist phages and suggests the presence of unknown mechanisms of intracellular resistance in the marine unicellular cyanobacteria. Furthermore, these findings indicate that the range for virus-mediated horizontal gene transfer extends beyond hosts to nonhost cyanobacterial cells.
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Beckett, Stephen J., e Hywel T. P. Williams. "Coevolutionary diversification creates nested-modular structure in phage–bacteria interaction networks". Interface Focus 3, n.º 6 (6 de dezembro de 2013): 20130033. http://dx.doi.org/10.1098/rsfs.2013.0033.
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Phage and their bacterial hosts are the most diverse and abundant biological entities in the oceans, where their interactions have a major impact on marine ecology and ecosystem function. The structure of interaction networks for natural phage–bacteria communities offers insight into their coevolutionary origin. At small phylogenetic scales, observed communities typically show a nested structure, in which both hosts and phages can be ranked by their range of resistance and infectivity, respectively. A qualitatively different multi-scale structure is seen at larger phylogenetic scales; a natural assemblage sampled from the Atlantic Ocean displays large-scale modularity and local nestedness within each module. Here, we show that such ‘nested-modular’ interaction networks can be produced by a simple model of host–phage coevolution in which infection depends on genetic matching. Negative frequency-dependent selection causes diversification of hosts (to escape phages) and phages (to track their evolving hosts). This creates a diverse community of bacteria and phage, maintained by kill-the-winner ecological dynamics. When the resulting communities are visualized as bipartite networks of who infects whom, they show the nested-modular structure characteristic of the Atlantic sample. The statistical significance and strength of this observation varies depending on whether the interaction networks take into account the density of the interacting strains, with implications for interpretation of interaction networks constructed by different methods. Our results suggest that the apparently complex community structures associated with marine bacteria and phage may arise from relatively simple coevolutionary origins.
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Laanto, Elina, Kati Mäkelä, Ville Hoikkala, Janne J. Ravantti e Lotta-Riina Sundberg. "Adapting a Phage to Combat Phage Resistance". Antibiotics 9, n.º 6 (29 de maio de 2020): 291. http://dx.doi.org/10.3390/antibiotics9060291.
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Phage therapy is becoming a widely recognized alternative for fighting pathogenic bacteria due to increasing antibiotic resistance problems. However, one of the common concerns related to the use of phages is the evolution of bacterial resistance against the phages, putatively disabling the treatment. Experimental adaptation of the phage (phage training) to infect a resistant host has been used to combat this problem. Yet, there is very little information on the trade-offs of phage infectivity and host range. Here we co-cultured a myophage FCV-1 with its host, the fish pathogen Flavobacterium columnare, in lake water and monitored the interaction for a one-month period. Phage resistance was detected within one day of co-culture in the majority of the bacterial isolates (16 out of the 18 co-evolved clones). The primary phage resistance mechanism suggests defense via surface modifications, as the phage numbers rose in the first two days of the experiment and remained stable thereafter. However, one bacterial isolate had acquired a spacer in its CRISPR (Clustered Regularly Interspaced Short Palindromic Repeat)-Cas locus, indicating that also CRISPR-Cas defense was employed in the phage-host interactions. After a week of co-culture, a phage isolate was obtained that was able to infect 18 out of the 32 otherwise resistant clones isolated during the experiment. Phage genome sequencing revealed several mutations in two open reading frames (ORFs) likely to be involved in the regained infectivity of the evolved phage. Their location in the genome suggests that they encode tail genes. Characterization of this evolved phage, however, showed a direct cost for the ability to infect several otherwise resistant clones—adsorption was significantly lower than in the ancestral phage. This work describes a method for adapting the phage to overcome phage resistance in a fish pathogenic system.
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Segundo-Arizmendi, Nallelyt, Dafne Arellano-Maciel, Abraham Rivera-Ramírez, Adán Manuel Piña-González, Gamaliel López-Leal e Efren Hernández-Baltazar. "Bacteriophages: A Challenge for Antimicrobial Therapy". Microorganisms 13, n.º 1 (7 de janeiro de 2025): 100. https://doi.org/10.3390/microorganisms13010100.
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Phage therapy, which involves the use of bacteriophages (phages) to combat bacterial infections, is emerging as a promising approach to address the escalating threat posed by multidrug-resistant (MDR) bacteria. This brief review examines the historical background and recent advancements in phage research, focusing on their genomics, interactions with host bacteria, and progress in medical and biotechnological applications. Additionally, we expose key aspects of the mechanisms of action, and therapeutic uses of phage considerations in treating MDR bacterial infections are discussed, particularly in the context of infections related to virus–bacteria interactions.
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Jończyk-Matysiak, Ewa, Beata Weber-Dąbrowska, Barbara Owczarek, Ryszard Międzybrodzki, Marzanna Łusiak-Szelachowska, Norbert Łodej e Andrzej Górski. "Phage-Phagocyte Interactions and Their Implications for Phage Application as Therapeutics". Viruses 9, n.º 6 (14 de junho de 2017): 150. http://dx.doi.org/10.3390/v9060150.
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Bichet, Marion C., Jack Adderley, Laura Avellaneda-Franco, Isabelle Magnin-Bougma, Natasha Torriero-Smith, Linden J. Gearing, Celine Deffrasnes et al. "Mammalian cells internalize bacteriophages and use them as a resource to enhance cellular growth and survival". PLOS Biology 21, n.º 10 (26 de outubro de 2023): e3002341. http://dx.doi.org/10.1371/journal.pbio.3002341.
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There is a growing appreciation that the direct interaction between bacteriophages and the mammalian host can facilitate diverse and unexplored symbioses. Yet the impact these bacteriophages may have on mammalian cellular and immunological processes is poorly understood. Here, we applied highly purified phage T4, free from bacterial by-products and endotoxins to mammalian cells and analyzed the cellular responses using luciferase reporter and antibody microarray assays. Phage preparations were applied in vitro to either A549 lung epithelial cells, MDCK-I kidney cells, or primary mouse bone marrow derived macrophages with the phage-free supernatant serving as a comparative control. Highly purified T4 phages were rapidly internalized by mammalian cells and accumulated within macropinosomes but did not activate the inflammatory DNA response TLR9 or cGAS-STING pathways. Following 8 hours of incubation with T4 phage, whole cell lysates were analyzed via antibody microarray that detected expression and phosphorylation levels of human signaling proteins. T4 phage application led to the activation of AKT-dependent pathways, resulting in an increase in cell metabolism, survival, and actin reorganization, the last being critical for macropinocytosis and potentially regulating a positive feedback loop to drive further phage internalization. T4 phages additionally down-regulated CDK1 and its downstream effectors, leading to an inhibition of cell cycle progression and an increase in cellular growth through a prolonged G1 phase. These interactions demonstrate that highly purified T4 phages do not activate DNA-mediated inflammatory pathways but do trigger protein phosphorylation cascades that promote cellular growth and survival. We conclude that mammalian cells are internalizing bacteriophages as a resource to promote cellular growth and metabolism.
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Zhang, Zheng, Fen Yu, Yuanqiang Zou, Ye Qiu, Aiping Wu, Taijiao Jiang e Yousong Peng. "Phage protein receptors have multiple interaction partners and high expressions". Bioinformatics 36, n.º 10 (25 de fevereiro de 2020): 2975–79. http://dx.doi.org/10.1093/bioinformatics/btaa123.
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Abstract Motivation Receptors on host cells play a critical role in viral infection. How phages select receptors is still unknown. Results Here, we manually curated a high-quality database named phageReceptor, including 427 pairs of phage–host receptor interactions, 341 unique viral species or sub-species and 69 bacterial species. Sugars and proteins were most widely used by phages as receptors. The receptor usage of phages in Gram-positive bacteria was different from that in Gram-negative bacteria. Most protein receptors were located on the outer membrane. The phage protein receptors (PPRs) were highly diverse in their structures, and had little sequence identity and no common protein domain with mammalian virus receptors. Further functional characterization of PPRs in Escherichia coli showed that they had larger node degrees and betweennesses in the protein–protein interaction network, and higher expression levels, than other outer membrane proteins, plasma membrane proteins or other intracellular proteins. These findings were consistent with what observed for mammalian virus receptors reported in previous studies, suggesting that viral protein receptors tend to have multiple interaction partners and high expressions. The study deepens our understanding of virus–host interactions. Availability and implementation phageReceptor is publicly available from: http://www.computationalbiology.cn/phageReceptor/index.html. Supplementary information Supplementary data are available at Bioinformatics online.
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Gillespie, James W., Liping Yang, Laura Maria De Plano, Murray A. Stackhouse e Valery A. Petrenko. "Evolution of a Landscape Phage Library in a Mouse Xenograft Model of Human Breast Cancer". Viruses 11, n.º 11 (26 de outubro de 2019): 988. http://dx.doi.org/10.3390/v11110988.
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Peptide-displayed phage libraries are billion-clone collections of diverse chimeric bacteriophage particles, decorated by genetically fused peptides built from a random combination of natural amino acids. Studying the molecular evolution of peptide-displayed libraries in mammalian model systems, using in vivo phage display techniques, can provide invaluable knowledge about the underlying physiology of the vasculature system, allow recognition of organ- and tissue-specific networks of protein–protein interactions, and provide ligands for targeted diagnostics and therapeutics. Recently, we discovered that landscape phage libraries, a specific type of multivalent peptide phage display library, expose on their surface comprehensive collections of elementary binding units (EBUs), which can form short linear motifs (SLiMs) that interact with functional domains of physiologically relevant proteins. Because of their unique structural and functional features, landscape phages can use an alternative mechanism of directed molecular evolution, i.e., combinatorial avidity selection. These discoveries fueled our interest in revisiting the in vivo evolution of phage displayed libraries using another format of display, i.e., landscape phages. In this study, we monitored the evolution of a landscape phage library in a mouse model with and without an implanted human breast cancer tumor xenograft. As expected, the multivalent architecture of landscape phage displayed proteins provided strong tissue selectivity and resulted in a huge diversity of tissue penetrating, chimeric phage particles. We identified several types of EBU interactions that evolved during the course of tissue distribution, which included interactions of EBUs with all tissue types, those EBUs that interacted selectively with specific organs or tissues with shared gene expression profiles or functionalities, and other EBUs that interacted in a tissue-selective manner. We demonstrated that landscape phage libraries are a rich collection of unique nanobioparticles that can be used to identify functional organ and tissue-binding elements after the evolution of a phage display library in vivo.
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Winans, James B., Benjamin R. Wucher e Carey D. Nadell. "Multispecies biofilm architecture determines bacterial exposure to phages". PLOS Biology 20, n.º 12 (22 de dezembro de 2022): e3001913. http://dx.doi.org/10.1371/journal.pbio.3001913.
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Numerous ecological interactions among microbes—for example, competition for space and resources, or interaction among phages and their bacterial hosts—are likely to occur simultaneously in multispecies biofilm communities. While biofilms formed by just a single species occur, multispecies biofilms are thought to be more typical of microbial communities in the natural environment. Previous work has shown that multispecies biofilms can increase, decrease, or have no measurable impact on phage exposure of a host bacterium living alongside another species that the phages cannot target. The reasons underlying this variability are not well understood, and how phage–host encounters change within multispecies biofilms remains mostly unexplored at the cellular spatial scale. Here, we study how the cellular scale architecture of model 2-species biofilms impacts cell–cell and cell–phage interactions controlling larger scale population and community dynamics. Our system consists of dual culture biofilms of Escherichia coli and Vibrio cholerae under exposure to T7 phages, which we study using microfluidic culture, high-resolution confocal microscopy imaging, and detailed image analysis. As shown previously, sufficiently mature biofilms of E. coli can protect themselves from phage exposure via their curli matrix. Before this stage of biofilm structural maturity, E. coli is highly susceptible to phages; however, we show that these bacteria can gain lasting protection against phage exposure if they have become embedded in the bottom layers of highly packed groups of V. cholerae in co-culture. This protection, in turn, is dependent on the cell packing architecture controlled by V. cholerae biofilm matrix secretion. In this manner, E. coli cells that are otherwise susceptible to phage-mediated killing can survive phage exposure in the absence of de novo resistance evolution. While co-culture biofilm formation with V. cholerae can confer phage protection to E. coli, it comes at the cost of competing with V. cholerae and a disruption of normal curli-mediated protection for E. coli even in dual species biofilms grown over long time scales. This work highlights the critical importance of studying multispecies biofilm architecture and its influence on the community dynamics of bacteria and phages.
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Molina, Felipe, Manuel Menor-Flores, Lucía Fernández, Miguel A. Vega-Rodríguez e Pilar García. "Systematic analysis of putative phage-phage interactions on minimum-sized phage cocktails". Scientific Reports 12, n.º 1 (14 de fevereiro de 2022). http://dx.doi.org/10.1038/s41598-022-06422-1.
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AbstractThe application of bacteriophages as antibacterial agents has many benefits in the “post-antibiotic age”. To increase the number of successfully targeted bacterial strains, phage cocktails, instead of a single phage, are commonly formulated. Nevertheless, there is currently no consensus pipeline for phage cocktail development. Thus, although large cocktails increase the spectrum of activity, they could produce side effects such as the mobilization of virulence or antibiotic resistance genes. On the other hand, coinfection (simultaneous infection of one host cell by several phages) might reduce the potential for bacteria to evolve phage resistance, but some antagonistic interactions amongst phages might be detrimental for the outcome of phage cocktail application. With this in mind, we introduce here a new method, which considers the host range and each individual phage-host interaction, to design the phage mixtures that best suppress the target bacteria while minimizing the number of phages to restrict manufacturing costs. Additionally, putative phage-phage interactions in cocktails and phage-bacteria networks are compared as the understanding of the complex interactions amongst bacteriophages could be critical in the development of realistic phage therapy models in the future.