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Добірка наукової літератури з теми "ESKAPE pathogen"

Автор: Grafiati
Опубліковано: 6 вересня 2023

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Статті в журналах з теми "ESKAPE pathogen"

1

Nasser, Mahfouz, Snehal Palwe, Ram Naresh Bhargava, Marc G. J. Feuilloley та Arun S. Kharat. "Retrospective Analysis on Antimicrobial Resistance Trends and Prevalence of β-lactamases in Escherichia coli and ESKAPE Pathogens Isolated from Arabian Patients during 2000–2020". Microorganisms 8, № 10 (21 жовтня 2020): 1626. http://dx.doi.org/10.3390/microorganisms8101626.

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The production of diverse and extended spectrum β-lactamases among Escherichia coli and ESKAPE pathogens is a growing threat to clinicians and public health. We aim to provide a comprehensive analysis of evolving trends of antimicrobial resistance and β-lactamases among E. coli and ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acine to bacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) in the Arabian region. A systematic review was conducted in Medline PubMed on papers published between January 2000 and February 2020 on countries in the Arab region showing different antibiotic resistance among E. coli and ESKAPE pathogens. A total of n = 119,144 clinical isolates were evaluated for antimicrobial resistance in 19 Arab countries. Among these clinical isolates, 74,039 belonged to E. coli and ESKAPE pathogen. Distribution of antibiotic resistance among E. coli and ESKAPE pathogens indicated that E. coli (n = 32,038) was the predominant pathogen followed by K. pneumoniae (n = 17,128), P. aeruginosa (n = 11,074), methicillin-resistant S. aureus (MRSA, n = 4370), A. baumannii (n = 3485) and Enterobacter spp. (n = 1574). There were no reports demonstrating Enterococcus faecium producing β-lactamase. Analyses revealed 19 out of 22 countries reported occurrence of ESBL (Extended-Spectrum β-Lactamase) producing E. coli and ESKAPE pathogens. The present study showed significantly increased resistance rates to various antimicrobial agents over the last 20 years; for instance, cephalosporin resistance increased from 37 to 89.5%, fluoroquinolones from 46.8 to 70.3%, aminoglycosides from 40.2 to 64.4%, mono-bactams from 30.6 to 73.6% and carbapenems from 30.5 to 64.4%. An average of 36.9% of the total isolates were reported to have ESBL phenotype during 2000 to 2020. Molecular analyses showed that among ESBLs and Class A and Class D β-lactamases, blaCTX-M and blaOXA have higher prevalence rates of 57% and 52.7%, respectively. Among Class B β-lactamases, few incidences of blaVIM 27.7% and blaNDM 26.3% were encountered in the Arab region. Conclusion: This review highlights a significant increase in resistance to various classes of antibiotics, including cephalosporins, β-lactam and β-lactamase inhibitor combinations, carbapenems, aminoglycosides and quinolones among E. coli and ESKAPE pathogens in the Arab region.
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Chapartegui-González, Itziar, María Lázaro-Díez, Santiago Redondo-Salvo, Jesús Navas, and José Ramos-Vivas. "Antimicrobial Resistance Determinants in Genomes and Plasmids from Acinetobacter baumannii Clinical Isolates." Antibiotics 10, no. 7 (June 22, 2021): 753. http://dx.doi.org/10.3390/antibiotics10070753.

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Acinetobacter baumannii is a Gram-negative coccoid rod species, clinically relevant as a human pathogen, included in the ESKAPE group. Carbapenem-resistant A. baumannii (CRAB) are considered by the World Health Organization (WHO) as a critical priority pathogen for the research and development of new antibiotics. Some of the most relevant features of this pathogen are its intrinsic multidrug resistance and its ability to acquire rapid and effective new resistant determinants against last-resort clinical antibiotics, mostly from other ESKAPE species. The presence of plasmids and mobile genetic elements in their genomes contributes to the acquisition of new antimicrobial resistance determinants. However, although A. baumannii has arisen as an important human pathogen, information about these elements is still not well understood. Current genomic analysis availability has increased our ability to understand the microevolution of bacterial pathogens, including point mutations, genetic dissemination, genomic stability, and pan- and core-genome compositions. In this work, we deeply studied the genomes of four clinical strains from our hospital, and the reference strain ATCC®19606TM, which have shown a remarkable ability to survive and maintain their effective capacity when subjected to long-term stress conditions. With that, our aim was presenting a detailed analysis of their genomes, including antibiotic resistance determinants and plasmid composition.
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Meurle, Tobias, Johannes Knaus, Agustin Barbano, Katharina Hoenes, Barbara Spellerberg, and Martin Hessling. "Photoinactivation of Staphylococci with 405 nm Light in a Trachea Model with Saliva Substitute at 37 °C." Healthcare 9, no. 3 (March 11, 2021): 310. http://dx.doi.org/10.3390/healthcare9030310.

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Анотація:
The globally observed rise in bacterial resistance against antibiotics has increased the need for alternatives to antibiotic treatments. The most prominent and important pathogen bacteria are the ESKAPE pathogens, which include among others Staphylococcus aureus, Klebsiella pneumoniae and Acinetobacter baumannii. These species cause ventilator-associated pneumonia (VAP), which accounts for 24% of all nosocomial infections. In this study we tested the efficacy of photoinactivation with 405 nm violet light under conditions comparable to an intubated patient with artificial saliva for bacterial suspension at 37 °C. A technical trachea model was developed to investigate the visible light photoinactivation of Staphylococcus carnosus as a non-pathogen surrogate of the ESKAPE pathogen S. aureus (MRSA). The violet light was coupled into the tube with a fiber optic setup. The performed tests proved, that photoinactivation at 37 °C is more effective with a reduction of almost 3 log levels (99.8%) compared to 25 °C with a reduction of 1.2 log levels. The substitution of phosphate buffered saline (PBS) by artificial saliva solution slightly increased the efficiency during the experimental course. The increased efficiency might be caused by a less favorable environment for bacteria due to for example the ionic composition.
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Vostal, Alexander C., Melissa Grance, Uzo Chukwuma, Carlos Morales, Charlotte Lanteri, Kalyani Telu, Edward Parmelee, John H. Powers, and Katrin Mende. "914. Epidemiology of Patients with ESKAPE Pathogen Bloodstream Infection in the US Military Health System." Open Forum Infectious Diseases 7, Supplement_1 (October 1, 2020): S492. http://dx.doi.org/10.1093/ofid/ofaa439.1102.

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Abstract Background Bloodstream infections (BSI) are associated with both inpatient mortality and substantial morbidity in the United States. We sought to characterize the epidemiology of BSIs with ESKAPE pathogens on patients served by the United States Military Healthcare System (MHS), which actively prospectively captures clinical and microbiological data from US service members and their beneficiaries. Methods We performed a retrospective analysis of MHS patients with blood cultures positive for ESKAPE pathogens (E. faecium, S. aureus, K. pneumoniae, A. baumannii, P. aeruginosa, and Enterobacter spp.), as well as Neisseria gonorrhoeae and Raoultella spp. between January 2010 and December 2015. Microbiological data from the Navy and Marine Core Public Health Center was retrospectively collated with clinical and demographic data from the MHS Data Repository. Results We identified 7,404 patients who experienced 8,791 episodes of ESKAPE (including N. gonorrhoeae and Raoultella spp.) BSI. The patients were predominately active duty (N=688) or retired (N=2,517) Armed Forces service members and their dependents (N=2,361). Further, 59.4% were male and 47.5% were >65 years old. A total of 5,594 (75.5%) of BSI episodes were associated with hospital admission, with an average length of stay of 14.9 days (SD of 27.5 days) and 47.4% (N=2,650) of those admissions were associated with an ICU stay averaging 8.6 days (SD of 18.0 days). The most common pathogens detected were E. coli (34.6%, N= 3,042) followed by S. aureus (28.0%,N=2,464), with 7.6% and 40.7% of isolates resistant to ceftriaxone and methicillin, respectively. We found a larger proportion of E. coli BSI in females (47.4% versus 26.2%) and S. aureus BSI in males (32% versus 21.9%). The frequency of A. baumannii BSI in younger patients, ages 18-30, was an average 4.5 fold higher than in older age groups (30-50, 50-65 and >65). Conclusion We noted epidemiological differences in the burden of ESKAPE pathogen BSIs, in various populations including sex and age specific risk factors in a population served by the MHS. Further work is underway to evaluate risk factors for infection and outcomes with pathogens with in vitro resistance controlling for factors such as age, gender, co-morbid diseases and severity of illness. Disclosures All Authors: No reported disclosures
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Seitz, Tamara, Sebastian Baumgartner, Christoph Wenisch, and Alexander Zoufaly. "115. Evaluation of the Clinical Impact of the T2MR for the Diagnosis of Bloodstream Infections." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S89. http://dx.doi.org/10.1093/ofid/ofz360.190.

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Abstract Background The EK-189 study evaluates the clinical impact of T2 magnetic resonance (T2MR) for rapid detection of bloodstream infections (BSI) caused by ESKAPE-pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Escherichia coli) compared with blood culture (BC). Here we present preliminary results from this ongoing study. Methods Patients newly admitted to an infectious diseases department with suspected blood stream infection with ESKAPE pathogens (based on predefined criteria) are included and randomized into BSI diagnosis with (a) T2MR and blood culture or (b) blood culture alone. Routine diagnostic workup including chest X-ray, complete laboratory workup (including blood count, C-reactive protein, interleukin-6) is performed in all patients. Antibiotic regimens are selected empirically based on suspected pathogens and are switched to targeted therapy at the discretion of the treating physician once a pathogen is detected. Outcome parameters include time to targeted (predefined) antibiotic therapy and time to discharge. Test characteristics of the T2MR compared with BC are also assessed. Results So far 44 patients were included (22 in each group). In 9/22 patients (41%) in the T2MR-group a pathogen was detected (4 Escherichia coli, 2 Klebsiella pneumoniae, 1 Staphylococcus aureus, 1 Pseudomonas aeruginosa and 1 Acinetobacter baumanii) and in 3/22 (14%) patients in the BC-group (all E. coli). The comparison of T2MR vs. BC is depicted in Table 1. Sensitivity and specificity of T2MR in comparison to BC were 100% and 64.7%. All positive results in T2MR were considered true positive results. The days until clinical improvement, the need for admission at ICU and the in-hospital mortality were similar in both groups. Conclusion The results from this preliminary analysis show that in patients with suspected BSI with ESKAPE pathogens, T2MR detects more pathogens than BC and potentially provides a quicker detection and shorter time to targeted therapy. Further analyses of this ongoing study with a larger sample size are needed to evaluate the impact of the use of T2MR on patient’s outcome Disclosures All authors: No reported disclosures.
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Skleenova, E. Yu, I. S. Azizov, Е. А. Shek, M. V. Edelstein, R. S. Kozlov, and A. V. Dekhnich. "Pseudomonas aeruginosa: the history of one of the most successful nosocomial pathogens in Russian hospitals." Clinical Microbiology and Antimicrobial Chemotherapy 20, no. 3 (2018): 164–71. http://dx.doi.org/10.36488/cmac.2018.3.164-171.

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Pseudomonas aeruginosa is recognized as one of the six most important pathogens in terms of antimicrobial resistance («ESKAPE» pathogens), and included by WHO in the group of microorganisms for which the need for development of new antimicrobial agents is crucial. In 2015, P. aeruginosa was the second (after Klebsiella spp.) most common nosocomial bacterial pathogen in Russia with the following resistance rates: amikacin – 45.2%, imipenem – 51.5%, meropenem – 53.3%, colistin – 2.2%, piperacillin/tazobactam – 61.4%, ceftazidime – 56.8%, ciprofloxacin – 61.2%. The majority of carbapenemase-producing isolates in Russia belong to the two epidemic lineages – CC235 and CC654.
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Hewitt, Curt, Katharina Weber, Danielle LeSassier, Anthony Kappell, Kathleen Schulte, Nicole Westfall, Nicolette Albright, et al. "Evaluating Metagenomic Analysis for Pathogen Transmission in Healthcare Settings." Infection Control & Hospital Epidemiology 41, S1 (October 2020): s224. http://dx.doi.org/10.1017/ice.2020.768.

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Background: The prevalence of healthcare-acquired infections (HAIs) and rising levels of antimicrobial resistance place a significant burden on modern healthcare systems. Cultures are typically used to track HAIs; however, culture methods provide limited information and are not applicable to all pathogens. Next-generation sequencing (NGS) can detect and characterize pathogens present within a sample, but few research studies have explored how NGS could be used to detect pathogen transmission events under HAI-relevant scenarios. The objective of this CDC-funded project was to evaluate and correlate sequencing approaches for pathogen transmission with standard culture-based analysis. Methods: We modeled pathogen transfer via hand contact using synthetic skin. These skin coupons were seeded with a community of commensal organisms to mimic the human skin microbiome. Pathogens were added at physiologically relevant high or low levels prior to skin-to-skin contact. The ESKAPE pathogens: E. faecium, S. aureus, K. pneumoniae, A. baumannii, P. aeruginosa, and Enterobacter spp plus C. difficile were employed because they are the most common antibiotic resistant HAIs. Pathogen transfer between skin coupons was measured following direct skin contact and fomite surface transmission. The effects of handwashing or fomite decontamination were also evaluated. Transferred pathogens were enumerated via culture to establish a robust data set against which DNA and RNA sequence analyses of the same samples could be compared. These data also provide a quantitative assessment of individual ESKAPE+C pathogen transfer rates in skin contact scenarios. Results: Metagenomic and metatranscriptomic analysis using custom analysis pipelines and reference databases successfully identified the commensal and pathogenic organisms present in each sample at the species level. This analysis also identified antibiotic resistance genes and plasmids. Metatranscriptomic analysis permitted not only gene identification but also confirmation of gene expression, a critical factor in the evaluation of antibiotic resistance. DNA analysis does not require cell viability, a key differentiator between sequencing and culturing reflected in simulated handwashing data. Sensitivity remains a key limitation of metagenomic analysis, as shown by the poor species identification and gene content characterization of pathogens present at low abundance within the simulated microbial community. Species level identification typically failed as ratios fell below 1:1,000 pathogen CFU:total community CFU. Conclusions: These findings demonstrate the strengths and weaknesses of NGS for molecular epidemiology. The data sets produced for this study are publicly available so they can be employed for future metagenomic benchmarking studies.Funding: NoneDisclosures: None
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Orosz, László, György Lengyel, Noel Ánosi, Lóránt Lakatos, and Katalin Burián. "Changes in resistance pattern of ESKAPE pathogens between 2010 and 2020 in the clinical center of University of Szeged, Hungary." Acta Microbiologica et Immunologica Hungarica 69, no. 1 (March 2, 2022): 27–34. http://dx.doi.org/10.1556/030.2022.01640.

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Abstract The acronym ESKAPE stands for six antibiotic-resistant bacterial pathogens namely, Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. Monitoring their resistance is an important task for clinical microbiology laboratories. Our aim was to analyze the resistance patterns of these bacteria over ten years in clinical samples of our department. We examined the sample types from which these pathogens were most frequently isolated. The incidence of tests with resistant results for each pathogen in aggregate and the most important subgroups of each was also analyzed. We have also intended to predict the local priorities amongst these pathogens. The results of 1,268,126 antibiotic susceptibility tests performed on a total of 70,099 isolates over this period were examined. Most strains were derived from urine, blood culture, trachea, vagina, wounds, and abscesses. Prevalence of ESKAPE bacteria increased between 2011 and 2020 however, the steepest intensifications were seen in the cases of K. pneumoniae and P. aeruginosa. The number of antibiotic susceptibility tests with resistant results has also increased over the decade but the most notable increase was detected in E. faecium and A. baumannii. Based on the calculation of antimicrobial resistance index for each pathogen, the most serious challenges for us at present are A. baumannii, P. aeruginosa, and E. faecium and their multi-resistant forms. The theoretical prediction of proportion of resistant tests between 2020 and 2030 in our care area draws attention to a worrying trend in the cases of vancomycin-resistant E. faecium and carbapenem-resistant A. baumannii strains.
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Mogokotleng, Ruth, Husna Ismail, Olga Perovic, and Sabelle Jallow. "A Retrospective Analysis of Culture-Confirmed Enterococci Bloodstream Infections in South Africa, 2016–2020: A Cross-Sectional Study." Tropical Medicine and Infectious Disease 8, no. 1 (December 27, 2022): 19. http://dx.doi.org/10.3390/tropicalmed8010019.

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(1) Background: The emergence of multidrug resistance enterococci is a major public health concern. This study aimed to determine the prevalence and antimicrobial resistance of enterococci isolated from blood cultures over a five-year period (2016–2020) at public hospitals in South Africa. (2): Methods: A retrospective analysis of clinical enterococci isolated from bloodstream infection samples at the South African public hospitals was conducted. The ESKAPE dataset from January 2016 to December 2020 was obtained from the central data warehouse (CDW) at the National Health Laboratory Service (NHLS). (3): Results: Following de-duplication, a total of 130,352/306,592 organisms isolated from blood cultures were identified as ESKAPE pathogens. In this study, K. pneumoniae (25%; 33,082/130,352), was the most frequently isolated pathogen from blood cultures, followed by S. aureus (23%; 29,922/130,352) and enterococci (16%; 21,339/130,352). Of the enterococci cases, about 43% (9132/21,339) of cases were from the infants aged (<1-year old) and 32% (6745/21,339) from the adult patients. No changes observed in vancomycin, teicoplanin, and linezolid susceptibility; however, E. faecium and E. faecalis blood culture isolates remained highly susceptible (>97%) to these antibiotics. (4): Conclusions: The current study revealed a significant increase of E. faecalis and E. faecium blood culture isolates as compared to the previous national ESKAPE data. Low vancomycin resistance was observed. Continuous monitoring of antimicrobial resistant Enterococcus species is warranted in South Africa.
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Karthick, Dr Mowna. "Pseudomonas aeruginosa: distribution and antibiotic profile of one of the ESKAPE pathogen." Tropical Journal of Pathology and Microbiology 5, no. 9 (September 30, 2019): 678–83. http://dx.doi.org/10.17511/jopm.2019.i09.10.

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Дисертації з теми "ESKAPE pathogen"

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Patel, Neha N. "A Cationic Zn-Containing Porphyrin Exhibits Potent Antibiotic Activity Against Cells and Biofilms of the ESKAPE Pathogen Pseudomonas aeruginosa: A Mechanistic Study." University of Dayton / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=dayton1618481857088121.

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Fleeman, Renee. "Discovering Antibacterial and Anti-Resistance Agents Targeting Multi-Drug Resistant ESKAPE Pathogens." Scholar Commons, 2017. http://scholarcommons.usf.edu/etd/6839.

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Antibiotic resistance has been a developing problem for mankind in recent decades and multi-drug resistant bacteria are now encountered that are resistant to all treatment options available. In 2014, the World Health Organization announced that this problem is driving us towards a “post-antibiotic era” that will change the face of modern medicine as we know it. If lack of novel antibiotic development and FDA approval continues, by the year 2050, 10 million people will die each year to an antimicrobial resistant bacterial infection. With lack of pharmaceutical industry involvement in developing novel antibiotics, the responsibility now lies within the academic institutions to identify potential novel therapeutics to fuel the antibiotic drug discovery pipeline. Combinatorial chemistry is one technique used to expedite the discovery process by assessing a large chemical space in a relatively short time when compared to traditional screening approaches. Combinatorial libraries can be screened using multiple approaches and has shown successful application towards many disease states. We initially discovered broad spectrum antibacterial bis-cyclic guanidines using combinatorial libraries and expanded on the knowledge of the physiochemical attributes necessary to inhibit Gram negative bacterial pathogens. Following this success, we continued to assess the combinatorial libraries for adjunctive therapeutics that potentiate the activity of obsolete clinical antibiotics. The polyamine efflux pump inhibitors discovered in this subsequent study prove the benefits of using the large chemical space provided in the combinatorial libraries to identify a variety of therapeutics. Our studies always begin with identifying an active compound and active compounds undergo hit-to-lead optimization. This optimization studies are of utmost importance in developing a novel antibacterial agent for therapeutic applications. Our medicinal chemistry work described here is proof of the success of careful structure activity analyses to optimize a hit scaffold to create a more effective antibacterial agent. Overall, our work described here reveals the potential role of academic institutions in fending off the impending “post-antibiotic era”.
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Giulianotti, Marcello. "The Use of Synthetic Mixture Based Libraries to Identify Hit Compounds for ESKAPE Pathogens, Leishmaniasis, and Inhibitors of Palmitoylation." Scholar Commons, 2016. http://scholarcommons.usf.edu/etd/6088.

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The goal of this work is to demonstrate the utility of using systematically formatted mixture based libraries as part of the drug discovery processes. While there are a number of different valid approaches for identifying hit and tool compounds, systematically formatted mixture based libraries, such as those described in this study, offer the ability to develop a significant amount of structure activity relationship data from the testing of very few samples. In support of this claim a review of recent developments in the area of systematically formatted mixture based libraries as well as three case studies are presented. The three case studies provide the detailed approach and results obtained from using systematically formatted mixture based libraries in programs focused on identifying broad spectrum antibiotics, therapeutics to treat leishmaniasis, and inhibitors of palmitoylation. In each of these three cases approximately 200 samples were utilized to survey millions of compounds in order to develop a series of hit and tool compounds as well as significant structure-activity relationship (SAR) data around the compounds identified. This information will be utilized in future studies to potentially uncover novel mechanisms of action for treating infections and diseases as well as developing therapeutics to treat the patients affect by them. So while systematically formatted mixture based libraries are not the only option for identifying hit or tool compounds they do provide a very efficient method that can be adapted to a variety of assay formats and therefor should be considered when conducting a screening campaign.
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Telussa, Rallya. "Reclaiming the Activity of Lost Therapeutics." Scholar Commons, 2016. http://scholarcommons.usf.edu/etd/6411.

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ESKAPE pathogens are notorious in causing nosocomial infections and escaping current antibiotic treatments. There has been a dramatic increase in nosocomial infections accompanied with a decrease in the number of antibiotics developed, leading to significant increase in morbidity and mortality among patients. In an attempt to combat this problem, derivatives of ciprofloxacin, rifabutin and beta-lactam antibiotics were synthesized and tested against the ESKAPE pathogens. From minimum inhibitory concentration assays, 4 ciprofloxacin analogs and 8 beta-lactam analogs were found to be effective against multiple bacterial species. Additionally, 12 rifabutin analogs and 23 beta-lactam analogs were potent against single bacterial species, primarily toward methicillin-resistant Staphylococcus aureus (MRSA) at a concentration of ≤ 25 µg mL-1. Based on the effectiveness against methicillin-resistant Staphylococcus aureus (MRSA), three rifabutin analogs were selected for further testing. Two rifabutin analogs (DU644 and DU645) were found to possess between a one to twofold mean increase of inhibitory activities, while the other rifabutin analogs (DU650) demonstrated up to a twofold decrease of inhibitory activity when compared to the parent drug. These compounds were then examined for their bactericidal and antibiofilm activities against MRSA. From these assays, we found that DU644 and DU645 were 4 times more bactericidal and antibiofilm against MRSA when compared to the parent drug. In addition, rpoB mutation validation results confirmed that modification of these rifabutin derivatives at the C3 and C4 positions, and bearing an imidazolyl ring carrying substituted spiropiperidyl ring, did not change their mechanism of action towards the beta-subunit of RNA polymerase. Cytotoxicity testing performed using human hepatocellular carcinoma epithelial cells (hepG2) showed that at concentrations ranged from 1.25 µg mL-1 to 25 µg mL-1, DU644 and DU645 showed very low toxicity. Collectively, structural drugs modifications of these obsolete drugs are able to restore their antibacterial activities against MRSA, which is notable as the most infectious nosocomial pathogen. Therefore, further development and application of rifabutin analogs might be beneficial for medical use to combat MRSA infections.
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Abdeen, Sanofar, Nilshad Salim, Najiba Mammadova, Corey M. Summers, Rochelle Frankson, Andrew J. Ambrose, Gregory G. Anderson, et al. "GroEL/ES inhibitors as potential antibiotics." Elsevier, 2016. http://hdl.handle.net/10150/618724.

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We recently reported results from a high-throughput screening effort that identified 235 inhibitors of the Escherichia coli GroEL/ES chaperonin system [Bioorg. Med. Chem. Lett. 2014, 24, 786]. As the GroEL/ES chaperonin system is essential for growth under all conditions, we reasoned that targeting GroEL/ES with small molecule inhibitors could be a viable antibacterial strategy. Extending from our initial screen, we report here the antibacterial activities of 22 GroEL/ES inhibitors against a panel of Gram-positive and Gram-negative bacteria, including E. coli, Bacillus subtilis, Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae. GroEL/ES inhibitors were more effective at blocking the proliferation of Gram-positive bacteria, in particular S. aureus, where lead compounds exhibited antibiotic effects from the low-lM to mid-nM range. While several compounds inhibited the human HSP60/10 refolding cycle, some were able to selectively target the bacterial GroEL/ES system. Despite inhibiting HSP60/10, many compounds exhibited low to no cytotoxicity against human liver and kidney cell lines. Two lead candidates emerged from the panel, compounds 8 and 18, that exhibit >50-fold selectivity for inhibiting S. aureus growth compared to liver or kidney cell cytotoxicity. Compounds 8 and 18 inhibited drug-sensitive and methicillin-resistant S. aureus strains with potencies comparable to vancomycin, daptomycin, and streptomycin, and are promising candidates to explore for validating the GroEL/ES chaperonin system as a viable antibiotic target.
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Voß, Eske [Verfasser]. "Untersuchungen zur Rolle intrazellulärer Rezeptoren bei der Induktion von antimikrobiellen Peptiden durch Pathogen assozziierte Moleküle (PAMs) / Eske Voß." Kiel : Universitätsbibliothek Kiel, 2008. http://d-nb.info/1019553642/34.

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Bhowmick, Jayantika. "CcdB : Stability, folding and application to design novel antibacterials." Thesis, 2020. https://etd.iisc.ac.in/handle/2005/5134.

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The primary amino acid sequence typically dictates the ultimate conformation of the protein. Mutations in the sequence demonstrate neutral, positive or negative effects on the structure-function relationship of the protein. Destabilising mutations often reduce the soluble levels of the protein in vivo, leading to complete or partial loss of its function. Global suppressors are diverse compensatory mutations that can alleviate the detrimental effects of multiple destabilised, inactive mutants, despite being physically distant from the site of the original inactive mutations. The molecular mechanisms responsible for suppression are still unknown, despite the characterisation of suppressors in several proteins since the late 1980s. Another modulator of a protein’s structure is the pH of the solution. It has long been known that proteins form molten globules at acidic pH conditions, which are compact denatured states with fluctuating tertiary structures. CcdB (Controller of Cell Division or Death B), a 101-residue homodimeric toxin which is a part of the CcdA:CcdB toxin:antitoxin module and poisons intracellular Gyrase, has been utilised as the model protein of choice in the course of the studies. Chapter 1 presents the importance of global suppressors, gives an overview of the role of pH on the protein’s structure and discusses various Gyrase inhibitors and outlines how the CcdB:Gyrase interaction can be utilised to design antibacterial peptides based on the toxin’s sequence. Chapter 2 provides a detailed thermodynamic and kinetic investigation of a global suppressor in CcdB. The studies show that the suppressor restores the stability and function of inactive mutants by marginally enhancing their apparent thermodynamic stabilities and lowering their unfolding rates. Chapter 3 shows the broad-spectrum antibacterial action of a novel CcdB-derived peptide on E.coli and pathogenic strains of S.aureus, S.Typhimurium, as well as a multi-drug resistant clinical isolate of A.baumannii. Chapter 4 reports a preliminary investigation of the low pH-induced molten globule-like state of CcdB using NMR spectroscopy.
MHRD, India
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Singh, Saumya. "Identifying Bacterial Species, Detecting Antibiotic Resistance and Susceptibilities in Clinical Samples Using Raman Spectroscopy." Thesis, 2022. https://etd.iisc.ac.in/handle/2005/6065.

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Over the past few decades, Raman spectroscopy has found enormous applications in biology and medicine. Raman micro-spectroscopy is highly sensitive to the structure and composition of molecules and their surrounding moieties present in a sample. This technique is label-free and non-invasive and offers a significant advantage over other methods involving minimal sample preparation and water interference. Raman spectroscopy combined with various chemometrics methods can provide molecular insights into several biochemical processes. This thesis discusses the application of Raman spectroscopy in identifying bacterial species, determining antibiotic susceptibility in clinical samples, and detecting phenotypic antibiotic resistance. The thesis begins with a brief introduction to the principle and instrumentation of Raman spectroscopy (Chapter 1). It provides a brief literature review of the applications of Raman spectroscopy in studying biological molecules. Chapter 2 of the thesis discusses the various Raman spectral data analysis approaches. Herbicides are ubiquitous in modern society and often co-occur with antibiotics in runways, sewage, and water bodies (Chapter 3). The herbicides used in this study are 2,4 D and Glyphosate, as these are the most widely used herbicides in agriculture worldwide. The study uses a group of isogenic mutants of E. coli, ∆lon, and ∆acrB, displaying different antibiotic susceptibilities. Combined with supervised machine learning methods, Raman spectroscopy could efficiently track the emergence of antibiotic resistance and confirm that the induction of antibiotic resistance is AcrB-dependent. Identifying bacterial species from clinical samples is often challenging. The current gold standard for identifying bacteria is time-intensive, laborious, and may provide incorrect results if the sample matrix is not entirely removed (Chapter 4). This part of the thesis demonstrates Raman spectroscopy-based identification of pathogens from clinical samples using deep learning at the single-cell level, especially for the ESKAPE class of pathogens. There has been an exponential rise in the emergence of antibiotic-resistant bacteria in the past few decades. Conventional methods for determining antibiotic susceptibilities do not provide information about antibiotic susceptibilities and fail to detect unknown resistant genes (Chapter 5). This part of the thesis shows the potential of Raman spectroscopy in differentiating various antibiotic-treated and untreated clinical isolates of Escherichia coli, Acinetobacter baumannii, and Enterobacter species into resistant and sensitive strains. Finally, the work done in the thesis and the future scope of the work has been briefed (Chapter 6). Overall, the thesis describes the applicability of Raman spectroscopy ranging from basic research to clinics.
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Частини книг з теми "ESKAPE pathogen"

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Kaur, Kawaljeet, Pramod Barathe, Sagar Reddy, Varsha Shriram, Abhijit Dey, Suresh Gosavi, and Vinay Kumar. "Nanoformulations Against Multidrug-Resistant Members of ESKAPE Pathogens." In Nanotechnology in the Life Sciences, 385–411. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-031-10220-2_12.

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Rajput, Akanksha, Kailash T. Bhamare, Adhip Mukhopadhyay, Amber Rastogi, Sakshi, and Manoj Kumar. "Efficacy of Anti-Biofilm Agents in Targeting ESKAPE Pathogens with a Focus on Antibiotic Drug Resistance." In ACS Symposium Series, 177–99. Washington, DC: American Chemical Society, 2020. http://dx.doi.org/10.1021/bk-2020-1374.ch010.

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Mundra, Surbhi, and Padam Singh. "Herbal Bioactives." In Advanced Pharmacological Uses of Medicinal Plants and Natural Products, 200–215. IGI Global, 2020. http://dx.doi.org/10.4018/978-1-7998-2094-9.ch010.

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Infection is caused in the human body due to the invasion of pathogenic microbes, their multiplication, and production of toxins. The ESKAPE pathogen comprises a group of six bacterial pathogens, namely Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. These pathogens are associated with the emerging cases of antimicrobial resistance to commonly used antibiotics such as penicillin, vancomycin, etc. Most of these pathogens are multidrug resistant, which is among the major threats to human health at present. The developing resistance to existing antibiotics imposes a burden on modern science to exercise the mechanism behind this and also the identification of novel targets to combat antimicrobial resistance. This chapter describes briefly about the mechanism of development of antimicrobial resistance and some herbal medications that can be used to combat the same. It also describes some of the traditional preventives that can be practiced to deal with infections.
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Rigane, Emna, and Susu M Zughaier. "Neisseria gonorrhoeae Ketol-Acid Reductoisomerase Is a Potential Therapeutic Target." In Bacterial Sexually Transmitted Infections - New Findings, Diagnosis, Treatment, and Prevention [Working Title]. IntechOpen, 2022. http://dx.doi.org/10.5772/intechopen.107993.

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The host-adapted human pathogen Neisseria gonorrhoeae is the causative agent of sexually transmitted infection gonorrhea. The increased emergence of gonorrhea infections worldwide, associated with the surging resistance to antimicrobial treatments is alarming. Antimicrobial resistance (AMR) is a global threat to human health and occur through various molecular mechanisms. This research aims to identify molecular therapeutic targets in N. gonorhoeae as a potential antibiotic adjuvant. This work is focused on ketol acid reductor-isomerase enzyme (KARI), an enzyme involved in the branched-chain amino acids biosynthesis. A BLASTp analysis revealed that KARI enzyme is highly conserved in N. gonorrhoeae strains and present in important bacterial pathogens including ESKAPE. Sequence alignment of different KARI proteins from various human bacterial pathogens and gut microbiota demonstrate that residues forming the active site and cofactors binding sites are conserved among all tested KARIs. A 3D homology-based model for gonococcal KARI was generated using Swiss model server and the KARI template from S. aureus. The generated 3D KARI model shows that this enzyme adapts a different conformation upon binding of cofactors, allowing the substrate binding and catalysis, while the active site adapts a closed state.
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Trastoy, Rocio, Lucia Blasco, German Bou, and Maria Tomas. "ighting antimicrobial resistance in ESKAPE pathogens." In Fighting Antimicrobial Resistance, 1–18. IAPC Publishing, 2018. http://dx.doi.org/10.5599/obp.15.9.

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Ramalingam, Karthikeyan, and Mohd Hashim Khan. "Antimicrobial Mechanisms and Mode of Actions of Nanoemulsion Against Drug-Resistant ESKAPE Pathogens." In Handbook of Research on Nanoemulsion Applications in Agriculture, Food, Health, and Biomedical Sciences, 142–68. IGI Global, 2022. http://dx.doi.org/10.4018/978-1-7998-8378-4.ch007.

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Анотація:
An enhancement of antibiotic resistance in bacteria is associated with increased morbidity, mortality, and health infrastructure and hospital care charges. The Infectious Diseases Society of America (IDSA) has highlighted a section of antibiotic resistant bacteria termed as ESKAPE pathogens. These pathogens are proficient in ‘escaping' the biocidal effect of antibiotics and mutually representing new paradigms in transmission of diseases, pathogenesis, and resistance in their genetic materials. Essential oil-based nanoemulsions (NEs) have great interest towards the “natural” therapies as potential antimicrobial agents. Thermodynamic properties and kinetically stable potential of biphasic system of nanoemulsion enable them to be used as an effective nano-carrier with controlled release at the targeted point. This chapter describes the mechanisms of ESKAPE pathogens and the mode of the mechanisms of antimicrobial action of nanoemulsions for the treatment of MDR human pathogens.
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Wang, Guangshun, Atul Verma, and Scott Reiling. "Antimicrobial peptide antibiotics against multidrug-resistant ESKAPE pathogens." In Antimicrobial Peptides, 237–59. Elsevier, 2023. http://dx.doi.org/10.1016/b978-0-323-85682-9.00012-x.

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Roy, Mrinalini, Surbhi Mewara, Prashant Sharma, Anupam Jyoti, Vijay Kumar Srivastava, and Sanket Kaushik. "Nanobiotics for the Treatment of MDR Infections." In Nanobiotechnology: Principles and Applications, 112–33. BENTHAM SCIENCE PUBLISHERS, 2023. http://dx.doi.org/10.2174/9789815123555123010008.

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Nanoparticles are those agents that are made-up of single or a combination of single or multiple materials which are very small in size ranging from 1 to 100 nanometers. Several studies reveal that nanoparticles have features that interact effectively with microorganisms and can help in treating multidrug-resistant organisms. These have intrinsic antimicrobial activity and are of various types broadly divided into organic and inorganic nanoparticles. Nanoparticles can engage with bacteria and travel across the bacterial cells and host cell membranes, and help treat ESKAPE pathogens which are among the most notorious multidrug resistant superbugs. These pathogens have MDR features and have multiple types of MDR mechanisms including drug inactivation/alteration, modification of drug binding sites/targets, reduced intracellular drug accumulation and biofilm formation. For targeting different types of MDR, there are multiple types of nanoparticles such as metal nanoparticles, nanostructures, leukocyte membrane-coated nanoparticles, red blood cell membrane-coated nanoparticles, cancer cell membrane-coated nanoparticles, and platelet membrane-coated nanoparticles among others. Antimicrobial nanobiotics identified and synthesized to date harbor a vast diversity of intrinsic and modified physicochemical properties and have applications in diagnostics. No technology is without its challenges and the same is true for nanobiotics. The major challenges in this field of nanobiotic-based therapeutics are their allergic responses, assembly and pharmacokinetics. This chapter will elaborate on the mechanisms of action of various types of nanobiotics present as cost-effective solutions useful in a variety of applications in the treatment of MDR pathogens with a special focus on ESKAPE pathogens.<br>
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Deb, Sujoy, and Sandipan Mukherjee. "Antimicrobial peptides: A possible strategy to combat ESKAPE pathogens." In Viral, Parasitic, Bacterial, and Fungal Infections, 107–13. Elsevier, 2023. http://dx.doi.org/10.1016/b978-0-323-85730-7.00051-5.

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Rangel, Karyne, and Salvatore Giovanni De-Simone. "Peptides with Therapeutic Potential against Acinetobacter baumanii Infections." In Antimicrobial Peptides [Working Title]. IntechOpen, 2022. http://dx.doi.org/10.5772/intechopen.100389.

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Анотація:
Antibiotic poly-resistance (multi drug-, extreme-, and pan-drug resistance) is a major global threat to public health. Unfortunately, in 2017, the World Health Organization (WHO) introduced the carbapenemresistant isolates in the priority pathogens list for which new effective antibiotics or new ways of treating the infections caused by them are urgently needed. Acinetobacter baumannii is one of the most critical ESKAPE pathogens for which the treatment of resistant isolates have caused severe problems; its clinically significant features include resistance to UV light, drying, disinfectants, and antibiotics. Among the various suggested options, one of the antimicrobial agents with high potential to produce new anti-Acinetobacter drugs is the antimicrobial peptides (AMPs). AMPs are naturally produced by living organisms and protect the host against pathogens as a part of innate immunity. The main mechanisms action of AMPs are the ability to cause cell membrane and cell wall damage, the inhibition of protein synthesis, nucleic acids, and the induction of apoptosis and necrosis. AMPs would be likely among the main anti-A. baumannii drugs in the post-antibiotic era. Also, the application of computer science to increase anti-A. baumannii activity and reduce toxicity is also being developed.
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Тези доповідей конференцій з теми "ESKAPE pathogen"

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Cincotti, Gabriella, Massimiliano Lucidi, Stefan G. Stanciu, Denis E. Tranca, Alina M. Holban, Lorenzo Nichele, and George A. Stanciu. "Correlative Multimodal Approach Based on Optical Near-Field and Topographic Imaging to Characterize the Morphology of ESKAPE Pathogen Bacteria at Nanoscale." In 2019 21st International Conference on Transparent Optical Networks (ICTON). IEEE, 2019. http://dx.doi.org/10.1109/icton.2019.8840036.

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Rahim, Muhammad KhairulAnwar Abdul, Muhamad Ramdzan Buyong, Nur Mas Ayu Jamaludin, Azrul Azlan Hamzah, Kim Shyong Siow, and Burhanuddin Yeop Majlis. "Characterization of Permittivity and Conductivity for ESKAPE Pathogens Detection." In 2018 IEEE International Conference on Semiconductor Electronics (ICSE). IEEE, 2018. http://dx.doi.org/10.1109/smelec.2018.8481278.

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Wang, Guangshun. "Design potent peptide antibiotics against the ESKAPE pathogens based on human antimicrobial peptide LL-37." In 4th International Electronic Conference on Medicinal Chemistry. Basel, Switzerland: MDPI, 2018. http://dx.doi.org/10.3390/ecmc-4-05882.

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Duplantier, Marine, Elodie Lohou, and Pascal Sonnet. "Development of new 2-heteroaryl-4-quinolones as potential antibiotics targeting multi-​drug resistant ESKAPEE pathogens." In 5th International Electronic Conference on Medicinal Chemistry. Basel, Switzerland: MDPI, 2019. http://dx.doi.org/10.3390/ecmc2019-06324.

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Duplantier, Marine, Elodie Lohou, and Pascal Sonnet. "Development of new 2-heteroaryl-4-quinolones as potential antivirulence agents targeting multi-drug resistant ESKAPEE pathogens." In 6th International Electronic Conference on Medicinal Chemistry. Basel, Switzerland: MDPI, 2020. http://dx.doi.org/10.3390/ecmc2020-07396.

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