scholarly journals Cationic antimicrobial peptides activate a two-component regulatory system, PmrA-PmrB, that regulates resistance to polymyxin B and cationic antimicrobial peptides in Pseudomonas aeruginosa

2003 ◽  
Vol 50 (1) ◽  
pp. 205-217 ◽  
Author(s):  
Joseph B. McPhee ◽  
Shawn Lewenza ◽  
Robert E. W. Hancock
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Peptides ◽  
Regulatory System ◽  
Polymyxin B ◽  
Cationic Antimicrobial Peptides ◽  
Two Component

scholarly journals PmrAB, a Two-Component Regulatory System of Pseudomonas aeruginosa That Modulates Resistance to Cationic Antimicrobial Peptides and Addition of Aminoarabinose to Lipid A

2004 ◽  
Vol 186 (2) ◽  
pp. 575-579 ◽  
Author(s):  
Samuel M. Moskowitz ◽  
Robert K. Ernst ◽  
Samuel I. Miller
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Peptides ◽  
Lipid A ◽  
Regulatory System ◽  
Signal Transduction System ◽  
Cationic Antimicrobial Peptides ◽  
Two Component ◽  
Serovar Typhimurium ◽  
Two Component Signal Transduction ◽  
Resistant Mutants

ABSTRACT Spontaneous polymyxin-resistant mutants of Pseudomonas aeruginosa were isolated. The mutations responsible for this phenotype were mapped to a two-component signal transduction system similar to PmrAB of Salmonella enterica serovar Typhimurium. Lipid A of these mutants contained aminoarabinose, an inducible modification that is associated with polymyxin resistance. Thus, P. aeruginosa possesses a mechanism that induces resistance to cationic antimicrobial peptides in response to environmental conditions.

scholarly journals The Staphylococcus aureus Two-Component Regulatory System, GraRS, Senses and Confers Resistance to Selected Cationic Antimicrobial Peptides

2011 ◽  
Vol 80 (1) ◽  
pp. 74-81 ◽  
Author(s):  
Soo-Jin Yang ◽  
Arnold S. Bayer ◽  
Nagendra N. Mishra ◽  
Michael Meehl ◽  
Nagender Ledala ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Positive Charge ◽  
Efflux Pump ◽  
Regulatory System ◽  
Polymyxin B ◽  
Cationic Antimicrobial Peptides ◽  
Two Component ◽  
Mrsa Strains ◽  
Reduced Surface

ABSTRACTThe two-component regulatory system, GraRS, appears to be involved in staphylococcal responses to cationic antimicrobial peptides (CAPs). However, the mechanism(s) by which GraRS is induced, regulated, and modulated remain undefined. In this study, we used two well-characterized MRSA strains (Mu50 and COL) and their respective mutants ofgraRandvraG(encoding the ABC transporter-dependent efflux pump immediately downstream ofgraRS), and show that (i) the expression of two key determinants of net positive surface charge (mprFanddlt) is dependent on the cotranscription of bothgraRandvraG, (ii) reduced expression ofmprFanddltingraRmutants was phenotypically associated with reduced surface-positive charge, (iii) this net reduction in surface-positive charge ingraRandvraGmutants, in turn, correlated with enhanced killing by a range of CAPs of diverse structure and origin, including those from mammalian platelets (tPMPs) and neutrophils (hNP-1) and from bacteria (polymyxin B), and (iv) the synthesis and translocation of membrane lysyl-phosphatidylglycerol (anmprF-dependent function) was substantially lower ingraRandvraGmutants than in parental strains. Importantly, the inducibility ofmprFanddlttranscription via thegraRS-vraFGpathway was selective, with induction by sublethal exposure to the CAPs, RP-1 (platelets), and polymyxin B, but not by other cationic molecules (hNP-1, vancomycin, gentamicin, or calcium-daptomycin). AlthoughgraRregulates expression ofvraG, the expression ofgraRwas codependent on an intact downstreamvraGlocus. Collectively, these data support an important role of thegraRSandvraFGloci in the sensing of and response to specific CAPs involved in innate host defenses.

scholarly journals Role of the LytSR Two-Component Regulatory System in Adaptation to Cationic Antimicrobial Peptides in Staphylococcus aureus

2013 ◽  
Vol 57 (8) ◽  
pp. 3875-3882 ◽  
Author(s):  
Soo-Jin Yang ◽  
Yan Q. Xiong ◽  
Michael R. Yeaman ◽  
Kenneth W. Bayles ◽  
Wessam Abdelhady ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Peptides ◽  
Regulatory System ◽  
Target Tissue ◽  
Adaptive Responses ◽  
Cationic Antimicrobial Peptide ◽  
Cationic Antimicrobial Peptides ◽  
Content Type ◽  
Response System ◽  
Two Component

ABSTRACTMany host defense cationic antimicrobial peptides (HDPs) perturb the staphylococcal cell membrane (CM) and alter transmembrane potential (ΔΨ) as key parts of their lethal mechanism. Thus, a sense-response system for detecting and mediating adaptive responses to such stresses could impact organism survival; theStaphylococcus aureusLytSR two-component regulatory system (TCRS) may serve as such a ΔΨ sensor. One well-known target of this system is thelrgABoperon, which, along with the relatedcidABCoperon, has been shown to be a regulator in the control of programmed cell death and lysis. We used an isogenic set ofS. aureusstrains: (i) UAMS-1, (ii) its isogenic ΔlytSand ΔlrgABmutants, and (iii) plasmid-complemented ΔlytSRand ΔlrgABmutants. The ΔlytSstrain displayed significantly increasedin vitrosusceptibilities to all HDPs tested (neutrophil-derived human neutrophil peptide 1 [hNP-1], platelet-derived thrombin-induced platelet microbicidal proteins [tPMPs], and the tPMP-mimetic peptide RP-1), as well as to calcium-daptomycin (DAP), a cationic antimicrobial peptide (CAP). In contrast, the ΔlrgABstrain exhibited no significant changes in susceptibilities to these cationic peptides, indicating that althoughlytSRpositively regulates transcription oflrgAB, increased HDP/CAP susceptibilities in the ΔlytSmutant werelrgABindependent. Further, parental UAMS-1 (but not the ΔlytSmutant) became more resistant to hNP-1 and DAP following pretreatment with carbonyl cyanidem-chlorophenylhydrazone (CCCP) (a CM-depolarizing agent). Of note,lytSR-dependent survival against CAP/HDP killing was not associated with changes in either surface positive charge, expression ofmprFanddlt, or CM fluidity. The ΔlytSstrain (but not the ΔlrgABmutant) displayed a significant reduction in target tissue survival in an endocarditis model during DAP treatment. Collectively, these results suggest that thelytSRTCRS plays an important role in adaptive responses ofS. aureusto CM-perturbing HDPs/CAPs, likely by functioning as a sense-response system for detecting subtle changes in ΔΨ.

scholarly journals Adaptive Resistance to the “Last Hope” Antibiotics Polymyxin B and Colistin in Pseudomonas aeruginosa Is Mediated by the Novel Two-Component Regulatory System ParR-ParS

2010 ◽  
Vol 54 (8) ◽  
pp. 3372-3382 ◽  
Author(s):  
Lucía Fernández ◽  
W. James Gooderham ◽  
Manjeet Bains ◽  
Joseph B. McPhee ◽  
Irith Wiegand ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Lipid A ◽  
Antimicrobial Agents ◽  
Regulatory System ◽  
Opportunistic Pathogen ◽  
Polymyxin B ◽  
Adaptive Resistance ◽  
Two Component ◽  
Induce Resistance ◽  
Two Component Systems

ABSTRACT As multidrug resistance increases alarmingly, polymyxin B and colistin are increasingly being used in the clinic to treat serious Pseudomonas aeruginosa infections. In this opportunistic pathogen, subinhibitory levels of polymyxins and certain antimicrobial peptides induce resistance toward higher, otherwise lethal, levels of these antimicrobial agents. It is known that the modification of lipid A of lipopolysaccharide (LPS) is a key component of this adaptive peptide resistance, but to date, the regulatory mechanism underlying peptide regulation in P. aeruginosa has remained elusive. The PhoP-PhoQ and PmrA-PmrB two-component systems, which control this modification under low-Mg2+ conditions, do not appear to play a major role in peptide-mediated adaptive resistance, unlike in Salmonella where PhoQ is a peptide sensor. Here we describe the identification and characterization of a novel P. aeruginosa two-component regulator affecting p olymyxin- a daptive r esistance, ParR-ParS (PA1799-PA1798). This system was required for activation of the arnBCADTEF LPS modification operon in the presence of subinhibitory concentrations of polymyxin, colistin, or the bovine peptide indolicidin, leading to increased resistance to various polycationic antibiotics, including aminoglycosides. This study highlights the complexity of the regulatory network controlling resistance to cationic antibiotics and host peptides in P. aeruginosa, which has major relevance in the development and deployment of cationic antimicrobials.

AgmR controls transcription of a regulon with several operons essential for ethanol oxidation in Pseudomonas aeruginosa ATCC 17933

Microbiology ◽  
2004 ◽  
Vol 150 (6) ◽  
pp. 1851-1857 ◽  
Author(s):  
Nicole Gliese ◽  
Viola Khodaverdi ◽  
Max Schobert ◽  
Helmut Görisch
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Ethanol Oxidation ◽  
Response Regulator ◽  
Regulatory System ◽  
Pyrroloquinoline Quinone ◽  
Kanamycin Resistance ◽  
Kanamycin Resistance Cassette ◽  
Two Component ◽  
Ethanol Dehydrogenase ◽  
Oxidation System

The response regulator AgmR was identified to be involved in the regulation of the quinoprotein ethanol oxidation system of Pseudomonas aeruginosa ATCC 17933. Interruption of the agmR gene by insertion of a kanamycin-resistance cassette resulted in mutant NG3, unable to grow on ethanol. After complementation with the intact agmR gene, growth on ethanol was restored. Transcriptional lacZ fusions were used to identify four operons which are regulated by the AgmR protein: the exaA operon encodes the pyrroloquinoline quinone (PQQ)-dependent ethanol dehydrogenase, the exaBC operon encodes a soluble cytochrome c 550 and an aldehyde dehydrogenase, the pqqABCDE operon carries the PQQ biosynthetic genes, and operon exaDE encodes a two-component regulatory system which controls transcription of the exaA operon. Transcription of exaA was restored by transformation of NG3 with a pUCP20T derivative carrying the exaDE genes under lac-promoter control. These data indicate that the AgmR response regulator and the exaDE two-component regulatory system are organized in a hierarchical manner. Gene PA1977, which appears to form an operon with the agmR gene, was found to be non-essential for growth on ethanol.

scholarly journals Polymyxin B Resistance and Biofilm Formation in Vibrio cholerae Are Controlled by the Response Regulator CarR

2015 ◽  
Vol 83 (3) ◽  
pp. 1199-1209 ◽  
Author(s):  
Kivanc Bilecen ◽  
Jiunn C. N. Fong ◽  
Andrew Cheng ◽  
Christopher J. Jones ◽  
David Zamorano-Sánchez ◽  
...  
Keyword(s):  
Vibrio Cholerae ◽  
Biofilm Formation ◽  
Lipid A ◽  
Response Regulator ◽  
Regulatory Region ◽  
Regulatory System ◽  
Polymyxin B ◽  
Content Type ◽  
Two Component ◽  
Antimicrobial Peptide Resistance

Two-component systems play important roles in the physiology of many bacterial pathogens.Vibrio cholerae's CarRS two-component regulatory system negatively regulates expression ofvps(Vibriopolysaccharide) genes and biofilm formation. In this study, we report that CarR confers polymyxin B resistance by positively regulating expression of thealmEFGgenes, whose products are required for glycine and diglycine modification of lipid A. We determined that CarR directly binds to the regulatory region of thealmEFGoperon. Similarly to acarRmutant, strains lackingalmE,almF, andalmGexhibited enhanced polymyxin B sensitivity. We also observed that strains lackingalmEor thealmEFGoperon have enhanced biofilm formation. Our results reveal that CarR regulates biofilm formation and antimicrobial peptide resistance inV. cholerae.

scholarly journals ZraP is a periplasmic molecular chaperone and a repressor of the zinc-responsive two-component regulator ZraSR

2012 ◽  
Vol 442 (1) ◽  
pp. 85-93 ◽  
Author(s):  
Corinne Appia-Ayme ◽  
Andrea Hall ◽  
Elaine Patrick ◽  
Shiny Rajadurai ◽  
Thomas A. Clarke ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Regulatory System ◽  
Enteric Bacteria ◽  
Polymyxin B ◽  
Regulatory Function ◽  
Cationic Antimicrobial Peptide ◽  
Envelope Stress ◽  
Two Component ◽  
Periplasmic Proteins ◽  
Zinc Concentrations

The bacterial envelope is the interface with the surrounding environment and is consequently subjected to a barrage of noxious agents including a range of compounds with antimicrobial activity. The ESR (envelope stress response) pathways of enteric bacteria are critical for maintenance of the envelope against these antimicrobial agents. In the present study, we demonstrate that the periplasmic protein ZraP contributes to envelope homoeostasis and assign both chaperone and regulatory function to ZraP from Salmonella Typhimurium. The ZraP chaperone mechanism is catalytic and independent of ATP; the chaperone activity is dependent on the presence of zinc, which is shown to be responsible for the stabilization of an oligomeric ZraP complex. Furthermore, ZraP can act to repress the two-component regulatory system ZraSR, which itself is responsive to zinc concentrations. Through structural homology, ZraP is a member of the bacterial CpxP family of periplasmic proteins, which also consists of CpxP and Spy. We demonstrate environmental co-expression of the CpxP family and identify an important role for these proteins in Salmonella's defence against the cationic antimicrobial peptide polymyxin B.

Cationic antimicrobial peptides elicit a complex stress response in Bacillus subtilis that involves ECF-type sigma factors and two-component signal transduction systems

Microbiology ◽  
2005 ◽  
Vol 151 (5) ◽  
pp. 1577-1592 ◽  
Author(s):  
Milla Pietiäinen ◽  
Marika Gardemeister ◽  
Maria Mecklin ◽  
Soile Leskelä ◽  
Matti Sarvas ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Bacillus Subtilis ◽  
Antimicrobial Peptides ◽  
Stress Responses ◽  
Signal Transduction Pathways ◽  
Synthetic Analogue ◽  
Cationic Antimicrobial Peptides ◽  
Component Systems ◽  
Two Component ◽  
Two Component Systems

Stress responses of Bacillus subtilis to membrane-active cationic antimicrobial peptides were studied. Global analysis of gene expression by DNA macroarray showed that peptides at a subinhibitory concentration activated numerous genes. A prominent pattern was the activation of two extracytoplasmic function sigma factor regulons, SigW and SigM. Two natural antimicrobial peptides, LL-37 and PG-1, were weak activators of SigW regulon genes, whereas their synthetic analogue poly-l-lysine was clearly a stronger activator of SigW. It was demonstrated for the first time that LL-37 is a strong and specific activator of the YxdJK two-component systems, one of the three highly homologous two-component systems sensing antimicrobial compounds. YxdJK regulates the expression of the YxdLM ABC transporter. The LiaRS (YvqCE) TCS was also strongly activated by LL-37, but its activation is not LL-37 specific, as was demonstrated by its activation with PG-1 and Triton X-100. Other strongly LL-37-induced genes included yrhH and yhcGHI. Taken together, the responses to cationic antimicrobial peptides revealed highly complex regulatory patterns and induction of several signal transduction pathways. The results suggest significant overlap between different stress regulons and interdependence of signal transduction pathways mediating stress responses.

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