Academic literature on the topic 'Phoq-phop'
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Journal articles on the topic "Phoq-phop"
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Sanowar, Sarah, Alexandre Martel, and Hervé Le Moual. "Mutational Analysis of the Residue at Position 48 in the Salmonella enterica Serovar Typhimurium PhoQ Sensor Kinase." Journal of Bacteriology 185, no. 6 (March 15, 2003): 1935–41. http://dx.doi.org/10.1128/jb.185.6.1935-1941.2003.
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ABSTRACT The PhoP/PhoQ two-component regulatory system of Salmonella enterica serovar Typhimurium plays an essential role in controlling virulence by mediating the adaptation to Mg2+ depletion. The pho-24 allele of phoQ harbors a single amino acid substitution (T48I) in the periplasmic domain of the PhoQ histidine kinase sensor. This mutation has been shown to increase net phosphorylation of the PhoP response regulator. We analyzed the effect on signaling by PhoP/PhoQ of various amino acid substitutions at this position (PhoQ-T48X [X = A, S, V, I, or L]). Mutations T48V, T48I, and T48L were found to affect signaling by PhoP/PhoQ both in vivo and in vitro. Mutations PhoQ-T48V and PhoQ-T48I increased both the expression of the mgtA::lacZ transcriptional fusion and the net phosphorylation of PhoP, conferring to cells a PhoP constitutively active phenotype. In contrast, mutation PhoQ-T48L barely responded to changes in the concentration of external Mg2+, in vivo and in vitro, conferring to cells a PhoP constitutively inactive phenotype. By analyzing in vitro the individual catalytic activities of the PhoQ-T48X sensors, we found that the PhoP constitutively active phenotype observed for the PhoQ-T48V and PhoQ-T48I proteins is solely due to decreased phosphatase activity. In contrast, the PhoP constitutively inactive phenotype observed for the PhoQ-T48L mutant resulted from both decreased autokinase activity and increased phosphatase activity. Our data are consistent with a model in which the residue at position 48 of PhoQ contributes to a conformational switch between kinase- and phosphatase-dominant states.
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Lejona, Sergio, María Eugenia Castelli, María Laura Cabeza, Linda J. Kenney, Eleonora García Véscovi, and Fernando C. Soncini. "PhoP Can Activate Its Target Genes in a PhoQ-Independent Manner." Journal of Bacteriology 186, no. 8 (April 15, 2004): 2476–80. http://dx.doi.org/10.1128/jb.186.8.2476-2480.2004.
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ABSTRACT The PhoP/PhoQ two-component system controls the extracellular magnesium depletion response in Salmonella enterica. Previous studies have shown that PhoP is unable to up-regulate its target genes in the absence of PhoQ function. In this work, we demonstrate that PhoP overexpression can substitute for PhoQ- and phosphorylation-dependent activation. Either a high concentration of PhoP or activation via phosphorylation stimulates PhoP self-association.
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Guina, Tina, Eugene C. Yi, Houle Wang, Murray Hackett, and Samuel I. Miller. "A PhoP-Regulated Outer Membrane Protease of Salmonella enterica Serovar Typhimurium Promotes Resistance to Alpha-Helical Antimicrobial Peptides." Journal of Bacteriology 182, no. 14 (July 15, 2000): 4077–86. http://dx.doi.org/10.1128/jb.182.14.4077-4086.2000.
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ABSTRACT The outer membrane protein contents of Salmonella enterica serovar Typhimurium strains with PhoP/PhoQ regulon mutations were compared by two-dimensional gel electrophoresis. At least 26 species of outer membrane proteins (OMPs) were identified as being regulated by PhoP/PhoQ activation. One PhoP/PhoQ-activated OMP was identified by semiautomated tandem mass spectrometry coupled with electronic database searching as PgtE, a member of theEscherichia coli OmpT and Yersinia pestis Pla family of outer membrane proteases. Salmonella PgtE expression promoted resistance to alpha-helical cationic antimicrobial peptides (α-CAMPs). Strains expressing PgtE cleaved C18G, an 18-residue α-CAMP present in culture medium, indicating that protease activity is likely to be the mechanism of OmpT-mediated resistance to α-CAMPs. PhoP/PhoQ did not regulate the transcription or export of PgtE, indicating that another PhoP/PhoQ-dependent mechanism is required for PgtE outer membrane localization. PgtE is a posttranscriptionally regulated component of the PhoP/PhoQ regulon that contributes toSalmonella resistance to innate immunity.
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Lesley, Joseph A., and Carey D. Waldburger. "Repression of Escherichia coli PhoP-PhoQ Signaling by Acetate Reveals a Regulatory Role for Acetyl Coenzyme A." Journal of Bacteriology 185, no. 8 (April 15, 2003): 2563–70. http://dx.doi.org/10.1128/jb.185.8.2563-2570.2003.
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ABSTRACT The PhoP-PhoQ two-component system regulates the transcription of numerous genes in response to changes in extracellular divalent cation concentration and pH. Here we demonstrate that the Escherichia coli PhoP-PhoQ two-component system also responds to acetate. Signaling by the E. coli PhoP-PhoQ system was repressed during growth in acetate (≥25 mM) in a PhoQ-dependent manner. The periplasmic sensor domain of PhoQ was not required for acetate to repress signaling. Acetate-mediated repression of the PhoP-PhoQ system was not related to changes in the intracellular concentration of acetate metabolites such as acetyl-phosphate or acetyladenylate. Genetic analysis of acetate metabolism pathways suggested that a perturbation of acetyl coenzyme A turnover was the cause of decreased PhoP-PhoQ signaling during growth in acetate. Consistent with this hypothesis, intracellular acetyl coenzyme A levels rose during growth in the presence of exogenous acetate. Acetyl coenzyme A inhibited the autokinase activity of PhoQ in vitro, suggesting that the in vivo repressing effect may be due to a direct inhibition mechanism.
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van Velkinburgh, Jennifer C., and John S. Gunn. "PhoP-PhoQ-Regulated Loci Are Required for Enhanced Bile Resistance in Salmonella spp." Infection and Immunity 67, no. 4 (April 1, 1999): 1614–22. http://dx.doi.org/10.1128/iai.67.4.1614-1622.1999.
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ABSTRACT As enteric pathogens, Salmonella spp. are resistant to the actions of bile. Salmonella typhimurium andSalmonella typhi strains were examined to better define the bile resistance phenotype. The MICs of bile for wild-typeS. typhimurium and S. typhi were 18 and 12%, respectively, and pretreatment of log-phase S. typhimurium with 15% bile dramatically increased bile resistance. Mutant strains of S. typhimurium andS. typhi lacking the virulence regulator PhoP-PhoQ were killed at significantly lower bile concentrations than wild-type strains, while strains with constitutively active PhoP were able to survive prolonged incubation with bile at concentrations of >60%. PhoP-PhoQ was shown to mediate resistance specifically to the bile components deoxycholate and conjugated forms of chenodeoxycholate, and the protective effect was not generalized to other membrane-active agents. Growth of both S. typhimurium and S. typhi in bile and in deoxycholate resulted in the induction or repression of a number of proteins, many of which appeared identical to PhoP-PhoQ-activated or -repressed products. The PhoP-PhoQ regulon was not induced by bile, nor did any of the 21 PhoP-activated or -repressed genes tested play a role in bile resistance. However, of the PhoP-activated or -repressed genes tested, two (prgC andprgH) were transcriptionally repressed by bile in the medium independent of PhoP-PhoQ. These data suggest that salmonellae can sense and respond to bile to increase resistance and that this response likely includes proteins that are members of the PhoP regulon. These bile- and PhoP-PhoQ-regulated products may play an important role in the survival of Salmonella spp. in the intestine or gallbladder.
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Liu, Wen, Xiang Li, Hong Qi, Yuning Wu, Jing Qu, Zhiyong Yin, Xuejuan Gao, Aidong Han, and Jianwei Shuai. "Biphasic regulation of transcriptional surge generated by the gene feedback loop in a two-component system." Bioinformatics 37, no. 17 (March 2, 2021): 2682–90. http://dx.doi.org/10.1093/bioinformatics/btab138.
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Abstract Motivation Transcriptional surges generated by two-component systems (TCSs) have been observed experimentally in various bacteria. Suppression of the transcriptional surge may reduce the activity, virulence and drug resistance of bacteria. In order to investigate the general mechanisms, we use a PhoP/PhoQ TCS as a model system to derive a comprehensive mathematical modeling that governs the surge. PhoP is a response regulator, which serves as a transcription factor under a phosphorylation-dependent modulation by PhoQ, a histidine kinase. Results Our model reveals two major signaling pathways to modulate the phosphorylated PhoP (P-PhoP) level, one of which promotes the generation of P-PhoP, while the other depresses the level of P-PhoP. The competition between the P-PhoP-promoting and the P-PhoP-depressing pathways determines the generation of the P-PhoP surge. Furthermore, besides PhoQ, PhoP is also a bifunctional modulator that contributes to the dynamic control of P-PhoP state, leading to a biphasic regulation of the surge by the gene feedback loop. In summary, the mechanisms derived from the PhoP/PhoQ system for the transcriptional surges provide a better understanding on such a sophisticated signal transduction system and aid to develop new antimicrobial strategies targeting TCSs. Availability and implementation https://github.com/jianweishuai/TCS. Supplementary information Supplementary data are available at Bioinformatics online.
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Eguchi, Yoko, Tadashi Okada, Shu Minagawa, Taku Oshima, Hirotada Mori, Kaneyoshi Yamamoto, Akira Ishihama, and Ryutaro Utsumi. "Signal Transduction Cascade between EvgA/EvgS and PhoP/PhoQ Two-Component Systems of Escherichia coli." Journal of Bacteriology 186, no. 10 (May 15, 2004): 3006–14. http://dx.doi.org/10.1128/jb.186.10.3006-3014.2004.
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ABSTRACT Transcriptional analysis of a constitutively active mutant of the EvgA/EvgS two-component system of Escherichia coli resulted in enhanced expression of 13 PhoP/PhoQ-regulated genes, crcA, hemL, mgtA, ompT, phoP, phoQ, proP, rstA, rstB, slyB, ybjG, yrbL, and mgrB. This regulatory network between the two systems also occurred as a result of overproduction of the EvgA regulator; however, enhanced transcription of the phoPQ genes did not further activate expression of the PhoP/PhoQ-regulated genes. These results demonstrated signal transduction from the EvgA/EvgS system to the PhoP/PhoQ system in E. coli and also identified the genes that required the two systems for enhanced expression. This is one example of the intricate signal transduction networks that are posited to exist in E. coli.
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Sanowar, Sarah, and Hervé Le Moual. "Functional reconstitution of the Salmonella typhimurium PhoQ histidine kinase sensor in proteoliposomes." Biochemical Journal 390, no. 3 (September 5, 2005): 769–76. http://dx.doi.org/10.1042/bj20050060.
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Two-component signal-transduction systems are widespread in bacteria. They are usually composed of a transmembrane histidine kinase sensor and a cytoplasmic response regulator. The PhoP/PhoQ two-component system of Salmonella typhimurium contributes to virulence by co-ordinating the adaptation to low concentrations of environmental Mg2+. Limiting concentrations of extracellular Mg2+ activate the PhoP/PhoQ phosphorylation cascade modulating the transcription of PhoP-regulated genes. In contrast, high concentrations of extracellular Mg2+ stimulate the dephosphorylation of the response regulator PhoP by the PhoQ kinase sensor. In the present study, we report the purification and functional reconstitution of PhoQHis, a PhoQ variant with a C-terminal His tag, into Escherichia coli liposomes. The functionality of PhoQHis was essentially similar to that of PhoQ as shown in vivo and in vitro. Purified PhoQHis was inserted into liposomes in a unidirectional orientation, with the sensory domain facing the lumen and the catalytic domain facing the extraluminal environment. Reconstituted PhoQHis exhibited all the catalytic activities that have been described for histidine kinase sensors. Reconstituted PhoQHis was capable of autokinase activity when incubated in the presence of Mg2+-ATP. The phosphoryl group could be transferred from reconstituted PhoQHis to PhoP. Reconstituted PhoQHis catalysed the dephosphorylation of phospho-PhoP and this activity was stimulated by the addition of extraluminal ADP.
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Tu, Jian, Boyan Huang, Yu Zhang, Yuxi Zhang, Ting Xue, Shaocan Li, and Kezong Qi. "Modulation of virulence genes by the two-component system PhoP-PhoQ in avian pathogenic Escherichia coli." Polish Journal of Veterinary Sciences 19, no. 1 (March 1, 2016): 31–40. http://dx.doi.org/10.1515/pjvs-2016-0005.
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Abstract Avian pathogenic Escherichia coli (APEC) infections are a very important problem in the poultry industry. PhoP-PhoQ is a two-component system that regulates virulence genes in APEC. In this study, we constructed strains that lacked the PhoP or PhoQ genes to assess regulation of APEC pathogenicity by the PhoP-PhoQ two-component system. The PhoP mutant strain AE18, PhoQ mutant strain AE19, and PhoP/PhoQ mutant strain AE20 were constructed by the Red homologous recombination method. Swim plates were used to evaluate the motility of the APEC strains, viable bacteria counting was used to assess adhesion and invasion of chick embryo fibroblasts, and Real-Time PCR was used to measure mRNA expression of virulence genes. We first confirmed that AE18, AE19, and AE20 were successfully constructed from the wild-type AE17 strain. AE18, AE19, and AE20 showed significant decreases in motility of 70.97%, 83.87%, and 37.1%, respectively, in comparison with AE17. Moreover, in comparison with AE17, AE18, AE19, and AE20 showed significant decreases of 63.11%, 65.42%, and 30.26%, respectively, in CEF cell adhesion, and significant decreases of 59.83%, 57.82%, and 37.90%, respectively, in CEF cell invasion. In comparison with AE17, transcript levels of sodA, polA, and iss were significantly decreased in AE18, while transcript levels of fimC and iss were significantly decreased in AE19. Our results demonstrate that deletion of PhoP or PhoQ inhibits invasion and adhesion of APEC to CEF cells and significantly reduces APEC virulence by regulating transcription of virulence genes.
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Yuan, Jing, Fan Jin, Timo Glatter, and Victor Sourjik. "Osmosensing by the bacterial PhoQ/PhoP two-component system." Proceedings of the National Academy of Sciences 114, no. 50 (November 28, 2017): E10792—E10798. http://dx.doi.org/10.1073/pnas.1717272114.
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The PhoQ/PhoP two-component system plays an essential role in the response of enterobacteria to the environment of their mammalian hosts. It is known to sense several stimuli that are potentially associated with the host, including extracellular magnesium limitation, low pH, and the presence of cationic antimicrobial peptides. Here, we show that the PhoQ/PhoP two-component systems ofEscherichia coliandSalmonellacan also perceive an osmotic upshift, another key stimulus to which bacteria become exposed within the host. In contrast to most previously established stimuli of PhoQ, the detection of osmotic upshift does not require its periplasmic sensor domain. Instead, we show that the activity of PhoQ is affected by the length of the transmembrane (TM) helix as well as by membrane lateral pressure. We therefore propose that osmosensing relies on a conformational change within the TM domain of PhoQ induced by a perturbation in cell membrane thickness and lateral pressure under hyperosmotic conditions. Furthermore, the response mediated by the PhoQ/PhoP two-component system was found to improve bacterial growth recovery under hyperosmotic stress, partly through stabilization of the sigma factor RpoS. Our findings directly link the PhoQ/PhoP two-component system to bacterial osmosensing, suggesting that this system can mediate a concerted response to most of the established host-related cues.
Dissertations / Theses on the topic "Phoq-phop"
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Le, Sage Valerie. "Ligand sensing and signal trasnduction by the two-component system PhoP/PhoQ." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=95624.
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The Citrobacter rodentium genome sequence contains a phoPQ operonhomologous (~79% identity) to that of S. typhimurium. We report that C. rodentiumPhoQ senses fluctuations in Mg2+ concentrations and acidic pH. Surprisingly, PhoQwas not activated by the presence of AMPs. However, activation by AMPs is observedwhen C. rodentium PhoP/PhoQ was expressed in as. typhimurium background. Weidentified an outer membrane protease of the omptin family that was responsible forinhibiting PhoQ activation by AMPs. In stark contrast to S. typhimurium, which relieson LPS modifications to resist AMPs, our results suggest that C. rodentium promotesresistance through a PhoP/PhoQ-dependent OM protease to inhibit disruption of theouter membrane by AMPs .La séquence du génome de Citrobacter rodentium présente un opéron phoPQ(~79% identité) homologue à celui de S. typhimurium. Nous avons déterminé quePhoQ de C. rodentium perçoit les variations de pH et en Mg2+ du milieu environnant.De manière surprenante, les PAMs ne causent aucune augmentation d'activité dePhoQ. Néeanmoins, lorsque le système PhoP/PhoQ de C. rodentium est exprimé chezS. typhimurium les PAMs activent PhoQ. Nous avons identifié une protéine de lamembrane externe appartenant à la famille des omptin qui est responsable del'inactivité de PhoQ en présence des P AMs. Ces résultats suggèrent que le mécanismede résistance aux PAMs de C. rodentium serait régulé par le système PhoP/PhoQ et une protéase qui empêcherait la destruction de la membrane externe par les P AMs. Cemécanisme de défense est différent de celui du système PhoP/PhoQ de S. typhimuriumqui repose essentiellement sur des modification du LPS .
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Salazar, Michael E. Jr (Michael Edward). "Induction kinetics of the PhoQ-PhoP two-component system in Escherichia coli." Thesis, Massachusetts Institute of Technology, 2016. http://hdl.handle.net/1721.1/104179.
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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2016.Cataloged from PDF version of thesis.
Includes bibliographical references.
Cells rely on signal transduction systems to sense and respond to changes in their enviroments. When a stimulus is present, the corresponding signal transduction system will activate and enact the appropriate biological response, often by modulating target gene expression. In many cases, the temporal dynamics of the activation of target gene expression in the presence of constant stimulus is complex, and often exhibits one or several pulses. How these complex temporal dynamics are regulated at the molecular level is unknown for many signal transduction systems. In this thesis, I discuss the molecular regulation of the temporal dynamics of PhoQ-PhoP induction in Escherichia coli. The PhoQ-PhoP pathway is a canonical two-component system that responds to low extracellular Mg'+, certain antimicrobial peptides, and potentially other unknown factors. Upon activation, the bifunctional histidine kinase PhoQ autophosphorylates and subsequently phosphotransfers to the response regulator PhoP, thereby activating it to increase transcription of PhoP target genes. Because PhoQ is bifunctional, PhoQ acts as a phosphatase on phosphorylated PhoP in the absence of stimulus, thereby keeping the system inactivated. When the PhoQ-PhoP system is strongly induced, PhoP target genes exhibit impulse kinetics, meaning gene expression increases to a maximal level and subsequently decreases to an eventual steady state. We discovered that this impulse response is caused by a negative feedback loop in which active PhoP transcribes mgrB, a gene encoding a small membrane protein that interacts directly with PhoQ to repress the output of the system. MgrB selectively inhibits the ability of PhoQ to phosphorylate PhoP, and permits PhoQ to act as a phosphatase on phosphorylated PhoP. This change in PhoQ activity causes a decrease in the level of active PhoP and the level of PhoP target genes. This thesis reveals how negative feedback loops and histidine kinase bifunctionality can drive the kinetics of two-component system induction in bacteria, and more generally explores how cells regulate changes in gene expression over time.
by Michael E. Salazar, Jr.
Ph. D.
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Gellatly, Shaan Lae. "Regulation of the PhoP-PhoQ two-component system in Pseudomonas aeruginosa and its role in virulence." Thesis, University of British Columbia, 2012. http://hdl.handle.net/2429/42991.
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Pseudomonas aeruginosa is an opportunistic bacterial pathogen that can cause severe
infections in individuals with underlying medical conditions. P. aeruginosa primarily infects at
epithelial surfaces where it interacts initially via type IV pili, flagella and LPS. Two component
regulatory systems control many aspects of pseudomonal physiology and mediate adaptation to
environmental changes including those that occur in the host. This thesis outlines the
contributions of these systems to the cytotoxicity to epithelial cells and sheds light on the
regulation mediated by the two-component sensor PhoQ. Systems that contributed to cytotoxicity
fell into several themes including motility, cyclic-di-GMP regulation, and carbon and nitrogen
utilization. Several genes controlled by PhoQ were shown to be dysregulated during infection of
lung epithelial cells, including upregulation of oprH-phoP-phoQ, the lipid A modification gene
arnB, and downregulation of a lipid A deacylase, pagL. Consistent with this, lipid A from a
phoQ mutant grown in varying magnesium concentrations displayed alterations. LPS of the
phoQ mutant revealed increased inflammatory properties as demonstrated by increased secretion
of the cytokines IL6, TNFalpha , and IL10 from PBMCs. The decrease in cytotoxicity of a phoQ
mutant correlated with a decrease in secretion of lipases and proteases when co-incubated with
cultured epithelial cells. These results suggest that the PhoP-PhoQ system might adapt the
bacterium to lung epithelia and that this might contribute to and be exacerbated by the selective
pressure of inhaled polymyxin therapeutics.
Unlike most sensor kinases that phosphorylate their cognate response regulators, PhoQ of P.
aeruginosa appears to act only as a phosphatase of its cognate regulator PhoP. Here it was
demonstrated that PhoP was not activated by PhoQ in a luminescence reporter screen. The sensor
kinase, RoxS, involved in regulation of the cyanide insensitive oxidase, was revealed as a
candidate phosphodonor to PhoP. Since mutation of roxS was able to reduce but not eliminate
expression from the oprH-phoP-phoQ operon, it is conceivable that other sensors contribute to
PhoP phosphorylation. It was also demonstrated that PhoP contributed to the known polymyxin
resistance of a phoQ mutant but only partially to cytotoxicity. These results emphasize the
complexity of the PhoP-PhoQ regulatory system.
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Rodrigues, Alves Lucas Bocchini. "Patogenicidade de Salmonella Gallinarum com deleção dos genes phoP e phoQ (SG∆phoPQ) em aves comerciais." Universidade Estadual Paulista (UNESP), 2017. http://hdl.handle.net/11449/152283.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
RESUMO – Salmonella Gallinarum (SG) é um patógeno hospedeiro-específico que causa o tifo aviário, doença sistêmica severa que é considerada uma das principais preocupações da indústria avícola mundial. Quando infecta a ave, SG utiliza mecanismos de evasão para sobreviver e replicar no interior de macrófagos. Nesse contexto, os genes phoPQ codificam o sistema regulatório de dois componentes (PhoPQ) que regula genes de virulência responsáveis pela adaptação de Salmonella spp. a fatores antimicrobianos como baixo pH, peptídeos antimicrobianos e baixas concentrações de cátions bivalentes. No presente estudo, objetivou-se investigar a função desses genes para SG. Assim, uma estirpe de SG com genes phoPQ defectivos (SG ∆phoPQ) foi construída e sua patogenicidade avaliada em aves poedeiras de 20 dias de vida susceptíveis ao tifo aviário. SG ∆phoPQ não causou sinais clínicos nem mortalidade em aves desafiadas oralmente, sendo não-patogênica. Ademais, essa estirpe não foi recuperada de fígados e baços. Por outro lado, aves desafiadas subcutaneamente com a estirpe mutante tiveram alterações patológicas discretas a moderadas e baixas contagens bacterianas em tecidos de fígado e baço. A partir dos dados, observa-se que SG ∆phoPQ é atenuado para aves o que sugere que ambos os genes são importantes durante a infecção sistêmica em aves por SG.
ABSTRACT – Salmonella Gallinarum (SG) is a host-restrict pathogen that causes fowl typhoid, a severe systemic disease that is one of the major concerns to the poultry industry worldwide. When infecting the bird, SG makes use of evasion mechanisms to survive and to replicate within macrophages. In this context, phoPQ genes encode a two-component regulatory system (PhoPQ) that regulates virulence genes responsible for adaptation of Salmonella spp. to antimicrobial factors such as low pH, antimicrobial peptides and deprivation of bivalent cations. Herein, we aimed to investigate the role of the mentioned genes to SG. Thus, a phoPQ-depleted SG strain (SG ∆phoPQ) was constructed and its virulence assessed in twenty-day-old laying hens susceptible to fowl typhoid. SG ∆phoPQ did cause neither clinical signs nor mortality in birds orally challenged, being non-pathogenic. Furthermore, this strain was not recovered from livers or spleens. On the other hand, chickens challenged subcutaneously with the mutant strain had discreet to moderate pathological changes and also low bacterial counts in liver and spleen tissues. These findings show that SG ∆phoPQ is attenuated to susceptible chickens and suggest that both genes are important during chicken systemic infection by SG.
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Coornaert, Audrey. "Etude de la régulation post-transcriptionnelle de l'expression du système à deux composants PhoQ-PhoP par les ARN régulateurs chez Escherichia coli." Paris 7, 2012. http://www.theses.fr/2012PA077129.
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Les bactéries ont développé diverses stratégies leur permettant de survivre aux brusques changements de leur environnement. Par exemple, les systèmes à deux composants (SDC) sont des régulateurs transcriptionnels majeurs: souvent, une kinase, stimulée dans des conditions spécifiques, active le régulateur transcriptionnel qui lui est associé, afin de permettre la régulation de l'expression de ses gènes cibles. PhoQ-PhoP est un SDC central, activé dans des conditions de faible concentration de magnésium, d'acidification du milieu ou encore par les peptides antimicrobiens. En réponse, il active l'expression de nombreux gènes. Les ARN régulateurs sont aussi un moyen rapide d'adaptation. Chez les bactéries, l'action d'un grand nombre d'entre eux dépend de la protéine chaperon à ARN Hfq. Leur mode d'action consiste à s'apparier directement à l'ARNm cible par complémentarité imparfaite de séquence. Il en résulte une régulation, positive ou négative, de la traduction et/ou de la stabilité de l'ARNm cible. Nous avons montré que MicA et GcvB, deux ARN régulateurs Hfq-dépendants, réprimaient directement l'expression dephoPQ en se fixant à la région de démarrage de la traduction dephoP, entrant ainsi en compétition avec la fixation du ribosome. Etonnamment, ils affectent différemment l'expression des gènes cibles de PhoP : alors que MicA, contrôlé par sigma E, réprime l'expression du régulon, GcvB a un effet plutôt activateur. Ce résultat troublant attend encore une explication, même s'il semble lié à un effet pléiotropique de GcvB dans la cellule. Nous avons mis en évidence un lien entre trois systèmes d'adaptation bactériens différents: les ARNreg, les SDC et les facteurs sigmaBacteria have developed many strategies allowing them to adapt and live in ever changing environments. Among them, two- component Systems are key regulators of transcription: in most cases, a histidine kinase protein, stimulated by specific signals, activates its cognate response regulator, leading to regulation of the expression of target genes. PhoQ-PhoP is one of those two-component Systems, and is activated by low extracellular magnesium concentration, low pH or antimicrobial peptides. In response, it activates the expression of dozens of genes involved in magnesium import, bacterial virulence or response to acid stress. Small regulatory RNAs are also involved in the rapid adaptation of gene expression to the environment. In bacteria, there is a particular class, whose activity is dependent on the RNA chaperone Hfq. They act by pairing with target mRNA(s) via imperfect duplexes and modify, either positively or negatively, target mRNA translation and/or stability. We have showed that MicA and GcvB, two Hfq-dependent small regulatory RNAs, directly dowriregulate PhoQ-PhoP synthesis by pairing with the translation initiation region of the first cistron ofphoPQ mRNA, thereby inhibiting binding of the small ribosomal subunit. Surprinsingly, these regulations differently affect expression of the PhoP regulon: MicA has, as expected, a negative effet on the regulon, while GcvB seems to have a positive effect. This unexpected result is still under investigation but seems to be related to a pleiotropic effect of GcvB in the cell. More generally, we highlighted a link between three different bacterial adaptative regulatory Systems: sRNA, two-component Systems and sigma factors
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Nordesjö, Olle. "Searching for novel protein-protein specificities using a combined approach of sequence co-evolution and local structural equilibration." Thesis, Uppsala universitet, Institutionen för biologisk grundutbildning, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-275040.
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Greater understanding of how we can use protein simulations and statistical characteristics of biomolecular interfaces as proxies for biological function will make manifest major advances in protein engineering. Here we show how to use calculated change in binding affinity and coevolutionary scores to predict the functional effect of mutations in the interface between a Histidine Kinase and a Response Regulator. These proteins participate in the Two-Component Regulatory system, a system for intracellular signalling found in bacteria. We find that both scores work as proxies for functional mutants and demonstrate a ~30 fold improvement in initial positive predictive value compared with choosing randomly from a sequence space of 160 000 variants in the top 20 mutants. We also demonstrate qualitative differences in the predictions of the two scores, primarily a tendency for the coevolutionary score to miss out on one class of functional mutants with enriched frequency of the amino acid threonine in one position.
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Kwasnicka, Agnieszka. "Identification of PhoP-PhoQ homologues in Pseudomonas aeruginosa responsible for regulation of the outer membrane protein OprH." Thesis, 1999. http://hdl.handle.net/2429/9660.
Full textAbstract:
Expression of the Pseudomonas aeruginosa outer membrane protein OprH is
induced in low magnesium growth conditions (Nicas and Hancock, 1980; 1983). This
protein has been proposed to play a role in stabilizing the outer membrane in the absence
of Mg²⁺ by interacting with LPS at sites where these cations would bind. Adaptation to
magnesium limitation in Salmonella typhimurium has been shown to occur through
activation of the two-component regulatory system, PhoP-PhoQ (Soncini et al., 1996).
Putative PhoP and PhoQ proteins were identified in the P. aeruginosa genome through
homology searches using the corresponding S. typhimurium protein sequences. The genes
encoding these proteins were located directly downstream of the gene encoding OprH.
Transcriptional linkage of oprH, phoP and phoQ was demonstrated and the hypothesis
that this system regulates expression of OprH in P. aeruginosa was tested in the
following study.
Through construction of aphoP null mutants and transformation of this mutant
with PhoP encoding plasmids, it was shown that PhoP is required for expression of OprH.
Furthermore, PhoP was demonstrated to be an activator of oprH, phoP and phoQ
transcription from a promoter upstream of oprH. In contrast, a phoQ null mutant showed
high-level, unregulated activation of oprH and phoP transcription and OprH expression.
Complementation of this mutant demonstrated a requirement for PhoQ in down
regulation of transcription and response to magnesium. Analysis of the oprH promoter
enabled identification of the start of transcription and delineation of the sequences
required for regulated OprH expression to within 90 basepairs of the ATG.
Book chapters on the topic "Phoq-phop"
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Miller, Samuel I. "PhoP/PhoQ: Regulating Salmonella Adaptation to Host Microenvironments." In Signal Transduction and Bacterial Virulence, 61–77. Berlin, Heidelberg: Springer Berlin Heidelberg, 1995. http://dx.doi.org/10.1007/978-3-662-22406-9_5.
Full textConference papers on the topic "Phoq-phop"
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Kravchenko, V. A., N. E. Gogoleva, A. N. Crook, Yu V. Dubo, Y. V. Gogolev, and E. A. Nikolaychik. "The role of the two-component system PhoQ / PhoP Pectobacterium carotovorum in interaction withhost-plant." In IX Congress of society physiologists of plants of Russia "Plant physiology is the basis for creating plants of the future". Kazan University Press, 2019. http://dx.doi.org/10.26907/978-5-00130-204-9-2019-235.
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Harari, Oscar, Coral del Val, and Igor Zwir. "Integrating network motifs into a genetic network: A case of study based on the Phop/PhoQ two-component system." In 2011 11th International Conference on Intelligent Systems Design and Applications (ISDA). IEEE, 2011. http://dx.doi.org/10.1109/isda.2011.6121851.
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