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Xiangkai Zhuge, Yu Sun, Feng Xue, Fang Tang, Jianluan Ren, Dezhi Li, Juanfang Wang, Min Jiang, Jianjun Dai
The extraintestinal pathogenic Escherichia coli (ExPEC) is a typical facultative intracellular bacterial pathogen. Sensing the environmental stimuli and undertaking adaptive change are crucial for ExPEC to successfully colonize in specific extraintestinal niches. The previous studies show that pathogens exploit two-component systems (TCSs) in response to the host environments during its infection. The PhoP/PhoQ is a typical TCS which is ubiquitous in Gram-negative bacteria. However, there is an incompletely understanding about critical regulatory roles of PhoP/PhoQ in ExPEC pathogenesis...
2018: Frontiers in Immunology
Casey C Fowler, Jorge E Galán
Salmonella Typhi is the cause of typhoid fever, a major global health concern. An essential virulence factor of this pathogen is typhoid toxin. In contrast to most AB-type toxins, typhoid toxin is exclusively expressed by intracellular bacteria. The regulatory networks that ensure this unique gene expression pattern are unknown. Here, we developed FAST-INSeq, a genome-wide screening approach to identify S. Typhi genes required for typhoid toxin expression within infected cells. We find that typhoid toxin expression is controlled by a silencing and counter-silencing mechanism through the opposing actions of the PhoP/PhoQ two-component regulatory system and the histone-like protein H-NS...
January 10, 2018: Cell Host & Microbe
Fang Dong, Lin Xia, Renfei Lu, Xin Zhao, Yiquan Zhang, Ying Zhang, Xinxiang Huang
Bacterial non-coding RNAs (ncRNAs), as important regulatory factors, are involved in many cellular processes, including virulence and protection against environmental stress. The 5' untranslated region (UTR) of malS (named malS-5'UTR), a regulatory ncRNA, increases the invasive capacity and influences histidine biosynthesis in Salmonella enterica serovar Typhi (S. Typhi). In this study, we found that overexpression of the malS-5'UTR decreased S. Typhi survival within macrophages. A microarray analysis of a strain overexpressing the malS-5'UTR revealed a significant increase in the mRNA levels of the atp operon...
February 2018: Microbial Pathogenesis
Sabine Delannoy, Laetitia Le Devendec, Eric Jouy, Patrick Fach, Djamel Drider, Isabelle Kempf
We studied a collection of 79 colistin-resistant Escherichia coli isolates isolated from diseased pigs in France between 2009 and 2013. We determined a number of phenotypic and genetic characters using broth microdilution to characterize their antimicrobial susceptibility. We performed pulse field gel electrophoresis (PFGE) to assess their genetic diversity and assign them to phylogroups. High-throughput real-time PCR micro-array was used to screen for a selection of genetic markers of virulence, and PCR and sequencing of the main recognized resistance genes allowed us to investigate the mechanisms of colistin resistance...
2017: Frontiers in Microbiology
Jing Yuan, Fan Jin, Timo Glatter, Victor Sourjik
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 of Escherichia coli and Salmonella can also perceive an osmotic upshift, another key stimulus to which bacteria become exposed within the host...
December 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
Matthew A Crawford, Debra J Fisher, Lisa M Leung, Sara Lomonaco, Christine Lascols, Antonio Cannatelli, Tommaso Giani, Gian Maria Rossolini, Yohei Doi, David R Goodlett, Marc W Allard, Shashi K Sharma, Erum Khan, Robert K Ernst, Molly A Hughes
The continued rise and spread of antimicrobial resistance among bacterial pathogens pose a serious challenge to global health. Countering antimicrobial-resistant pathogens requires a multifaceted effort that includes the discovery of novel therapeutic approaches. Here, we establish the capacity of the human CXC chemokines CXCL9 and CXCL10 to kill multidrug-resistant Gram-negative bacteria, including New Delhi metallo-beta-lactamase-1-producing Klebsiella pneumoniae and colistin-resistant members of the family Enterobacteriaceae that harbor the mobile colistin resistance protein MCR-1 and thus possess phosphoethanolamine-modified lipid A...
November 14, 2017: MBio
Xiaoyu Qing, Ami De Weerdt, Marc De Maeyer, Hans Steenackers, Arnout Voet
The response regulator PhoP, which is part of the PhoP/PhoQ two-component system, regulates the expression of multiple genes involved in controlling virulence in Salmonella enterica serovar Typhimurium and other species of Gram-negative bacteria. Modulating the phosphorylation-mediated dimerization in the receiver domain may interfere with the transcriptional function of PhoP. In this study, we analyzed the therapeutic potential of the PhoP receiver domain by exploring it as a potential target for drug design...
January 1, 2018: Biochemical and Biophysical Research Communications
Jeongjoon Choi, Eduardo A Groisman
Acidic conditions, such as those inside phagosomes, stimulate the intracellular pathogen Salmonella enterica to activate virulence genes. The sensor PhoQ responds to a mildly acidic pH by phosphorylating, and thereby activating, the virulence regulator PhoP. This PhoP/PhoQ two-component system is conserved in a subset of Gram-negative bacteria. PhoQ is thought to be sufficient to activate PhoP in mildly acidic pH. However, we found that the Salmonella-specific protein UgtL, which was horizontally acquired by Salmonella before the divergence of S...
August 29, 2017: Science Signaling
Mohammad Qadi, Sofía Izquierdo-Rabassa, Margalida Mateu Borrás, Antonio Doménech-Sánchez, Carlos Juan, Joanna B Goldberg, Robert E W Hancock, Sebastián Albertí
Pseudomonas aeruginosa adaptation to survive in the host hinges on its ability to probe the environment and respond appropriately. Rapid adaptation is often mediated by two-component regulatory systems, such as the PhoP/PhoQ system that responds to Mg2+ ion concentration. However, there is limited information about the role of PhoQ in P. aeruginosa bloodstream infections. We used a murine model of systemic infection to test the virulence of a PhoQ-deficient mutant. Mutation of PhoQ impaired the virulence and the ability to cause bacteremia of P...
October 2017: Environmental Microbiology
Xiao-Yu Qing, Hans Steenackers, Tom Venken, Marc De Maeyer, Arnout Voet
The response regulator PhoP is part of the PhoP/PhoQ two-component system, which is responsible for regulating the expression of multiple genes involved in controlling virulence, biofilm formation, and resistance to antimicrobial peptides. Therefore, modulating the transcriptional function of the PhoP protein is a promising strategy for developing new antimicrobial agents. There is evidence suggesting that phosphorylation-mediated dimerization in the regulatory domain of PhoP is essential for its transcriptional function...
June 9, 2017: Molecular Informatics
Bao-Yu Peng, Yue Pan, Ru-Jiao Li, Jin-Wei Wei, Fang Liang, Li Wang, Fang-Fang Wang, Wei Qian
How essential, regulatory genes originate and evolve is intriguing because mutations of these genes not only lead to lethality in organisms, but also have pleiotropic effects since they control the expression of multiple downstream genes. Therefore, the evolution of essential, regulatory genes is not only determined by genetic variations of their own sequences, but also by the biological function of downstream genes and molecular mechanisms of regulation. To understand the origin of essential, regulatory genes, experimental dissection of the complete regulatory cascade is needed...
August 2017: Genetics
Mohd Fakharul Zaman Raja Yahya, Zazali Alias, Saiful Anuar Karsani
Salmonella typhimurium is an important biofilm-forming bacteria. It is known to be resistant to a wide range of antimicrobials. The present study was carried out to evaluate the effects of dimethyl sulfoxide (DMSO) against S. typhimurium biofilm and investigate whole-cell protein expression by biofilm cells following treatment with DMSO. Antibiofilm activities were assessed using pellicle assay, crystal violet assay, colony-forming unit counting and extracellular polymeric substance (EPS) matrix assay whilst differential protein expression was investigated using a combination of one dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis, tandem mass spectrometry and bioinformatics...
August 2017: Protein Journal
Katarina Novović, Anika Trudić, Snežana Brkić, Zorica Vasiljević, Milan Kojić, Deana Medić, Ivana Ćirković, Branko Jovčić
Twenty-seven colistin-resistant, carbapenemase-producing Klebsiella pneumoniae isolates were identified from hospitals in Serbia. All isolates were bla CTX-M-15 positive; ST101, ST888, ST437, ST336, and ST307 were bla OXA-48 positive; and ST340 was bla NDM-1 positive. ST307 had an insertion, and ST336 had a premature stop codon in the mgrB gene. Amino acid substitutions were detected in PmrAB of isolates ST101, ST888, ST336, and ST307. The mcr-1 and mcr-2 were not detected. An increase in phoP , phoQ , and pmrK gene transcription was detected for all sequence types...
May 2017: Antimicrobial Agents and Chemotherapy
Adam L Clayton, Shinichiro Enomoto, Yinghua Su, Colin Dale
Many bacteria utilize two-component systems consisting of a sensor kinase and a transcriptional response regulator to detect environmental signals and modulate gene expression for adaptation. The response regulator PhoP and its cognate sensor kinase PhoQ compose a two-component system known for its role in responding to low levels of Mg2+ , Ca2+ , pH and to the presence of antimicrobial peptides and activating the expression of genes involved in adaptation to host association. Compared with their free-living relatives, mutualistic insect symbiotic bacteria inhabit a static environment where the requirement for sensory functions is expected to be relaxed...
March 2017: Molecular Microbiology
Trung-Kien Tran, Qiang-Qiang Han, Yixin Shi, Lin Guo
In pathogenic bacteria, the two-component regulatory systems (TCSs) play important roles in signal transduction and regulation of their pathogenesis. Here, we used quantitative proteomic methods to comparatively analyze functional networks under the control of the RstA/RstB system versus the PhoP/PhoQ system in Salmonella typhimurium. By comparing the proteomic profile from a wild-type strain to that from a ΔrstB strain or a ΔphoPQ strain under a condition known to activate these TCSs, we found that the levels of 159 proteins representing 6...
December 2016: Biochimica et Biophysica Acta
R R Cheng, O Nordesjö, R L Hayes, H Levine, S C Flores, J N Onuchic, F Morcos
Two-component signaling (TCS) is the primary means by which bacteria sense and respond to the environment. TCS involves two partner proteins working in tandem, which interact to perform cellular functions whereas limiting interactions with non-partners (i.e., cross-talk). We construct a Potts model for TCS that can quantitatively predict how mutating amino acid identities affect the interaction between TCS partners and non-partners. The parameters of this model are inferred directly from protein sequence data...
December 2016: Molecular Biology and Evolution
Sebastián Riquelme, Macarena Varas, Camila Valenzuela, Paula Velozo, Nicolás Chahin, Paulina Aguilera, Andrea Sabag, Bayron Labra, Sergio A Álvarez, Francisco P Chávez, Carlos A Santiviago
The social amoeba Dictyostelium discoideum has proven to be a useful model for studying relevant aspects of the host-pathogen interaction. In this work, D. discoideum was used as a model to study the ability of Salmonella Typhimurium to survive in amoebae and to evaluate the contribution of selected genes in this process. To do this, we performed infection assays using axenic cultures of D. discoideum co-cultured with wild-type S. Typhimurium and/or defined mutant strains. Our results confirmed that wild-type S...
2016: Frontiers in Microbiology
François Guérin, Christophe Isnard, Clara Sinel, Philippe Morand, Anne Dhalluin, Vincent Cattoir, Jean-Christophe Giard
OBJECTIVES: Aims of this study were to: (i) evaluate whether the cluster membership could have an impact on hetero-resistance phenotype to colistin in the Enterobacter cloacae complex (ECC); and (ii) determine the genetic mechanism of colistin hetero-resistance in ECC. METHODS: A collection of 124 clinical isolates belonging to 13 clusters were used to analyse the hetero-resistance phenotype (MICs were determined using the broth microdilution method, Etest and population analysis profiling)...
November 2016: Journal of Antimicrobial Chemotherapy
Srujana S Yadavalli, Jeffrey N Carey, Rachel S Leibman, Annie I Chen, Andrew M Stern, Manuela Roggiani, Andrew M Lippa, Mark Goulian
Antimicrobial peptides are an important component of the molecular arsenal employed by hosts against bacteria. Many bacteria in turn possess pathways that provide protection against these compounds. In Escherichia coli and related bacteria, the PhoQ/PhoP signalling system is a key regulator of this antimicrobial peptide defence. Here we show that treating E. coli with sublethal concentrations of antimicrobial peptides causes cells to filament, and that this division block is controlled by the PhoQ/PhoP system...
2016: Nature Communications
Michael E Salazar, Anna I Podgornaia, Michael T Laub
In Escherichia coli and other γ-proteobacteria, the PhoQ-PhoP two-component signaling system responds to low extracellular Mg(++) and cationic antimicrobial peptides. On transition to inducing conditions, the expression of PhoP-dependent genes increases rapidly, but then decays to a new, intermediate steady-state level, a phenomenon often referred to as partial adaptation. The molecular basis for this partial adaptation has been unclear. Here, using time-lapse fluorescence microscopy to examine PhoP-dependent gene expression in individual E...
November 2016: Molecular Microbiology
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