scholarly journals Identification of Hopanoid Biosynthesis Genes Involved in Polymyxin Resistance in Burkholderia multivorans

2011 ◽  
Vol 56 (1) ◽  
pp. 464-471 ◽  
Author(s):  
Rebecca J. Malott ◽  
Barbara R. Steen-Kinnaird ◽  
Tracy D. Lee ◽  
David P. Speert
Keyword(s):  
Burkholderia Cepacia ◽  
Polymyxin B ◽  
Biosynthesis Gene Cluster ◽  
Content Type ◽  
Reading Frame ◽  
Burkholderia Multivorans ◽  
Mutant Strains ◽  
Outer Membrane Permeability ◽  
Increased Susceptibility ◽  
Lps Binding

ABSTRACTA major challenge to clinical therapy ofBurkholderia cepaciacomplex (Bcc) pulmonary infections is their innate resistance to a broad range of antimicrobials, including polycationic agents such as aminoglycosides, polymyxins, and cationic peptides. To identify genetic loci associated with this phenotype, a transposon mutant library was constructed inB. multivoransATCC 17616 and screened for increased susceptibility to polymyxin B. Compared to the parent strain, mutant 26D7 exhibited 8- and 16-fold increases in susceptibility to polymyxin B and colistin, respectively. Genetic analysis of mutant 26D7 indicated that the transposon inserted into open reading frame (ORF) Bmul_2133, part of a putative hopanoid biosynthesis gene cluster. A strain with a mutation in another ORF in this cluster, Bmul_2134, was constructed and named RMI19. Mutant RMI19 also had increased polymyxin susceptibility. Hopanoids are analogues of eukaryotic sterols involved in membrane stability and barrier function. Strains with mutations in Bmul_2133 and Bmul_2134 showed increased permeability to 1-N-phenylnaphthylamine in the presence of increasing concentrations of polymyxin, suggesting that the putative hopanoid biosynthesis genes are involved in stabilizing outer membrane permeability, contributing to polymyxin resistance. Results from a dansyl-polymyxin binding assay demonstrated that polymyxin B does not bind well to the parent or mutant strains, suggesting that Bmul_2133 and Bmul_2134 contribute to polymyxin B resistance by a mechanism that is independent of lipopolysaccharide (LPS) binding. Through this work, we propose a role for hopanoid biosynthesis as part of the multiple antimicrobial resistance phenotype in Bcc bacteria.

scholarly journals Fosmidomycin Decreases Membrane Hopanoids and Potentiates the Effects of Colistin on Burkholderia multivorans Clinical Isolates

2014 ◽  
Vol 58 (9) ◽  
pp. 5211-5219 ◽  
Author(s):  
Rebecca J. Malott ◽  
Chia-Hung Wu ◽  
Tracy D. Lee ◽  
Trevor J. Hird ◽  
Nathan F. Dalleska ◽  
...  
Keyword(s):  
Burkholderia Cepacia ◽  
Polymyxin B ◽  
Inhalation Therapy ◽  
Pulmonary Infections ◽  
Binding Assays ◽  
Intrinsic Resistance ◽  
Content Type ◽  
Burkholderia Multivorans ◽  
Liquid Chromatography Tandem Mass ◽  
Antimicrobial Synergy

ABSTRACTBurkholderia cepaciacomplex (Bcc) pulmonary infections in people living with cystic fibrosis (CF) are difficult to treat because of the extreme intrinsic resistance of most isolates to a broad range of antimicrobials. Fosmidomycin is an antibacterial and antiparasitic agent that disrupts the isoprenoid biosynthesis pathway, a precursor to hopanoid biosynthesis. Hopanoids are involved in membrane stability and contribute to polymyxin resistance in Bcc bacteria. Checkerboard MIC assays determined that although isolates of the Bcc speciesB. multivoranswere highly resistant to treatment with fosmidomycin or colistin (polymyxin E), antimicrobial synergy was observed in certain isolates when the antimicrobials were used in combination. Treatment with fosmidomycin decreased the MIC of colistin for isolates as much as 64-fold to as low as 8 μg/ml, a concentration achievable with colistin inhalation therapy. A liquid chromatography-tandem mass spectrometry technique was developed for the accurate quantitative determination of underivatized hopanoids in total lipid extracts, and bacteriohopanetetrol cyclitol ether (BHT-CE) was found to be the dominant hopanoid made byB. multivorans. The amount of BHT-CE made was significantly reduced upon fosmidomycin treatment of the bacteria. Uptake assays with 1-N-phenylnaphthylamine were used to determine that dual treatment with fosmidomycin and colistin increases membrane permeability, while binding assays with boron-dipyrromethene-conjugated polymyxin B illustrated that the addition of fosmidomycin had no impact on polymyxin binding. This work indicates that pharmacological suppression of membrane hopanoids with fosmidomycin treatment can increase the susceptibility of certain clinicalB. multivoransisolates to colistin, an agent currently in use to treat pulmonary infections in CF patients.

scholarly journals Polymyxin Susceptibility in Pseudomonas aeruginosa Linked to the MexXY-OprM Multidrug Efflux System

2015 ◽  
Vol 59 (12) ◽  
pp. 7276-7289 ◽  
Author(s):  
Keith Poole ◽  
Calvin Ho-Fung Lau ◽  
Christie Gilmour ◽  
Youai Hao ◽  
Joseph S. Lam
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Resistance Mechanism ◽  
Polymyxin B ◽  
Wild Type ◽  
Multidrug Efflux ◽  
Efflux System ◽  
Content Type ◽  
Polymyxin E ◽  
Increased Susceptibility ◽  
Multidrug Efflux System

ABSTRACTThe ribosome-targeting antimicrobial, spectinomycin (SPC), strongly induced themexXYgenes of the MexXY-OprM multidrug efflux system inPseudomonas aeruginosaand increased susceptibility to the polycationic antimicrobials polymyxin B and polymyxin E, concomitant with a decrease in expression of the polymyxin resistance-promoting lipopolysaccharide (LPS) modification loci,arnBCADTEFand PA4773-74. Consistent with the SPC-promoted reduction inarnand PA4773-74 expression being linked tomexXY, expression of these LPS modification loci was moderated in a mutant constitutively expressingmexXYand enhanced in a mutant lacking the efflux genes. Still, the SPC-mediated increase in polymyxin susceptibility was retained in mutants lackingarnBand/or PA4773-74, an indication that their reduced expression in SPC-treated cells does not explain the enhanced polymyxin susceptibility. That the polymyxin susceptibility of a mutant strain lackingmexXYwas unaffected by SPC exposure, however, was an indication that the unknown polymyxin resistance ‘mechanism’ is also influenced by the MexXY status of the cell. In agreement with SPC and MexXY influencing polymyxin susceptibility as a result of changes in the LPS target of these agents, SPC treatment yielded a decline in common polysaccharide antigen (CPA) synthesis in wild-typeP. aeruginosabut not in the ΔmexXYmutant. A mutant lacking CPA still showed the SPC-mediated decline in polymyxin MICs, however, indicating that the loss of CPA did not explain the SPC-mediated MexXY-dependent increase in polymyxin susceptibility. It is possible, therefore, that some additional change in LPS promoted by SPC-inducedmexXYexpression impacted CPA synthesis or its incorporation into LPS and that this was responsible for the observed changes in polymyxin susceptibility.

scholarly journals Development of a Multiple-Locus Variable-Number Tandem-Repeat Typing Scheme for Genetic Fingerprinting of Burkholderia cenocepacia and Application to Nationwide Epidemiological Analysis

2014 ◽  
Vol 53 (2) ◽  
pp. 398-409 ◽  
Author(s):  
Christine Segonds ◽  
Michelle Thouverez ◽  
Antoine Barthe ◽  
Nadège Bossuet-Greif ◽  
Lenka Tisseyre ◽  
...  
Keyword(s):  
Tandem Repeat ◽  
Burkholderia Cepacia ◽  
Genetic Relatedness ◽  
Variable Number Tandem Repeat ◽  
Cost Effective ◽  
Variable Number ◽  
Discriminatory Power ◽  
Burkholderia Cenocepacia ◽  
Content Type ◽  
Burkholderia Multivorans

Organisms of theBurkholderia cepaciacomplex are especially important pathogens in cystic fibrosis (CF), with a propensity for patient-to-patient spread and long-term respiratory colonization.B. cenocepaciaandBurkholderia multivoransaccount for the majority of infections in CF, and major epidemic clones have been recognized throughout the world. The aim of the present study was to develop and evaluate a multilocus variable-number tandem-repeat (VNTR) analysis (MLVA) scheme forB. cenocepacia. Potential VNTR loci were identified upon analysis of the annotated genome sequences ofB. cenocepaciastrains AU1054, J2315, and MCO-3, and 10 of them were selected on the basis of polymorphisms and size. A collection of 100B. cenocepaciastrains, including epidemiologically related and unrelated strains, as well as representatives of the major epidemic lineages, was used to evaluate typeability, epidemiological concordance, and the discriminatory power of MLVA-10 compared with those of pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Longitudinal stability was assessed by testing 39 successive isolates from 14 patients. Typeability ranged from 0.91 to 1, except for that of one marker, which was not amplified in 53% of theB. cenocepaciaIIIA strains. The MLVA types were shown to be stable in chronically colonized patients and within outbreak-related strains, with excellent epidemiological concordance. Epidemic and/or globally distributed lineages (epidemic Edinburgh-Toronto electrophoretic type 12 [ET-12], sequence type 32 [ST-32], ST-122, ST-234, and ST-241) were successfully identified. Conversely, the discriminatory power of MLVA was lower than that of PFGE or MLST, although PFGE variations within the epidemic lineages sometimes masked their genetic relatedness. In conclusion, MLVA represents a promising cost-effective first-line tool inB. cenocepaciasurveillance.

scholarly journals Characterization of the AmpC β-Lactamase fromBurkholderia multivorans

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Scott A. Becka ◽  
Elise T. Zeiser ◽  
Melissa D. Barnes ◽  
Magdalena A. Taracila ◽  
Kevin Nguyen ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Active Site ◽  
Burkholderia Cepacia ◽  
Single Amino Acid ◽  
Amino Acid Substitutions ◽  
Enzyme Complex ◽  
Active Site Residues ◽  
Content Type ◽  
Burkholderia Multivorans

ABSTRACTBurkholderia multivoransis a member of theBurkholderia cepaciacomplex, a group of >20 related species of nosocomial pathogens that commonly infect individuals suffering from cystic fibrosis. β-Lactam antibiotics are recommended as therapy for infections due toB.multivorans, which possesses two β-lactamase genes,blapenAandblaAmpC. PenA is a carbapenemase with a substrate profile similar to that of theKlebsiella pneumoniaecarbapenemase (KPC); in addition, expression of PenA is inducible by β-lactams inB.multivorans. Here, we characterize AmpC fromB.multivoransATCC 17616. AmpC possesses only 38 to 46% protein identity with non-BurkholderiaAmpC proteins (e.g., PDC-1 and CMY-2). Among 49 clinical isolates ofB.multivorans, we identified 27 different AmpC variants. Some variants possessed single amino acid substitutions within critical active-site motifs (Ω loop and R2 loop). Purified AmpC1 demonstrated minimal measurable catalytic activity toward β-lactams (i.e., nitrocefin and cephalothin). Moreover, avibactam was a poor inhibitor of AmpC1 (Kiapp> 600 μM), and acyl-enzyme complex formation with AmpC1 was slow, likely due to lack of productive interactions with active-site residues. Interestingly, immunoblotting using a polyclonal anti-AmpC antibody revealed that protein expression of AmpC1 was inducible inB.multivoransATCC 17616 after growth in subinhibitory concentrations of imipenem (1 μg/ml). AmpC is a unique inducible class C cephalosporinase that may play an ancillary role inB.multivoranscompared to PenA, which is the dominant β-lactamase inB.multivoransATCC 17616.

scholarly journals Exploring the Role of the Ω-Loop in the Evolution of Ceftazidime Resistance in the PenA β-Lactamase from Burkholderia multivorans, an Important Cystic Fibrosis Pathogen

2016 ◽  
Vol 61 (2) ◽  
Author(s):  
Krisztina M. Papp-Wallace ◽  
Scott A. Becka ◽  
Magdalena A. Taracila ◽  
Elise T. Zeiser ◽  
Julian A. Gatta ◽  
...  
Keyword(s):  
Amino Acid ◽  
Burkholderia Cepacia ◽  
Clinical Isolates ◽  
Dynamics Simulation ◽  
Single Amino Acid ◽  
Amino Acid Substitutions ◽  
Biochemical Basis ◽  
Content Type ◽  
Burkholderia Multivorans

ABSTRACT The unwelcome evolution of resistance to the advanced generation cephalosporin antibiotic, ceftazidime is hindering the effective therapy of Burkholderia cepacia complex (BCC) infections. Regrettably, BCC organisms are highly resistant to most antibiotics, including polymyxins; ceftazidime and trimethoprim-sulfamethoxazole are the most effective treatment options. Unfortunately, resistance to ceftazidime is increasing and posing a health threat to populations susceptible to BCC infection. We found that up to 36% of 146 tested BCC clinical isolates were nonsusceptible to ceftazidime (MICs ≥ 8 μg/ml). To date, the biochemical basis for ceftazidime resistance in BCC is largely undefined. In this study, we investigated the role of the Ω-loop in mediating ceftazidime resistance in the PenA β-lactamase from Burkholderia multivorans, a species within the BCC. Single amino acid substitutions were engineered at selected positions (R164, T167, L169, and D179) in the PenA β-lactamase. Cell-based susceptibility testing revealed that 21 of 75 PenA variants engineered in this study were resistant to ceftazidime, with MICs of >8 μg/ml. Under steady-state conditions, each of the selected variants (R164S, T167G, L169A, and D179N) demonstrated a substrate preference for ceftazidime compared to wild-type PenA (32- to 320-fold difference). Notably, the L169A variant hydrolyzed ceftazidime significantly faster than PenA and possessed an ∼65-fold-lower apparent Ki (Ki app) than that of PenA. To understand why these amino acid substitutions result in enhanced ceftazidime binding and/or turnover, we employed molecular dynamics simulation (MDS). The MDS suggested that the L169A variant starts with the most energetically favorable conformation (−28.1 kcal/mol), whereas PenA possessed the most unfavorable initial conformation (136.07 kcal/mol). In addition, we observed that the spatial arrangement of E166, N170, and the hydrolytic water molecules may be critical for enhanced ceftazidime hydrolysis by the L169A variant. Importantly, we found that two clinical isolates of B. multivorans possessed L169 amino acid substitutions (L169F and L169P) in PenA and were highly resistant to ceftazidime (MICs ≥ 512 μg/ml). In conclusion, substitutions in the Ω-loop alter the positioning of the hydrolytic machinery as well as allow for a larger opening of the active site to accommodate the bulky R1 and R2 side chains of ceftazidime, resulting in resistance. This analysis provides insights into the emerging phenotype of ceftazidime-resistant BCC and explains the evolution of amino acid substitutions in the Ω-loop of PenA of this significant clinical pathogen.

scholarly journals Burkholderia cepacia Complex Contact-Dependent Growth Inhibition Systems Mediate Interbacterial Competition

2019 ◽  
Vol 201 (12) ◽  
Author(s):  
Tanya Myers-Morales ◽  
A. Elizabeth Oates ◽  
Matthew S. Byrd ◽  
Erin C. Garcia
Keyword(s):  
Cystic Fibrosis ◽  
Growth Inhibition ◽  
Burkholderia Cepacia ◽  
Gram Negative Bacteria ◽  
Immunity Protein ◽  
Gram Negative ◽  
Content Type ◽  
Burkholderia Multivorans ◽  
Dependent Growth ◽  
Contact Dependent Growth Inhibition

ABSTRACT Burkholderia species, including opportunistic pathogens in the Burkholderia cepacia complex (Bcc), have genes to produce contact-dependent growth inhibition (CDI) system proteins. CDI is a phenomenon in which Gram-negative bacteria use the toxic C terminus of a polymorphic surface-exposed exoprotein, BcpA, to inhibit the growth of susceptible bacteria upon direct cell-cell contact. Production of a small immunity protein, BcpI, prevents autoinhibition. Although CDI systems appear widespread in Gram-negative bacteria, their function has been primarily examined in several model species. Here we demonstrate that genes encoding predicted CDI systems in Bcc species exhibit considerable diversity. We also show that Burkholderia multivorans, which causes pulmonary infections in patients with cystic fibrosis, expresses genes that encode two CDI systems, both of which appear distinct from the typical Burkholderia-type CDI system. Each system can mediate intrastrain interbacterial competition and contributes to bacterial adherence. Surprisingly, the immunity-protein-encoding bcpI gene of CDI system 1 could be mutated without obvious deleterious effects. We also show that nonpathogenic Burkholderia thailandensis uses CDI to control B. multivorans growth during coculture, providing one of the first examples of interspecies CDI and suggesting that CDI systems could be manipulated to develop therapeutic strategies targeting Bcc pathogens. IMPORTANCE Competition among bacteria affects microbial colonization of environmental niches and host organisms, particularly during polymicrobial infections. The Bcc is a group of environmental bacteria that can cause life-threatening opportunistic infections in patients who have cystic fibrosis or are immunocompromised. Understanding the mechanisms used by these bacterial pathogens to compete with one another may lead to the development of more effective therapies. Findings presented here demonstrate that a Bcc species, Burkholderia multivorans, produces functional CDI system proteins and that growth of this pathogen can be controlled by CDI system proteins produced by neighboring Burkholderia cells.

scholarly journals OmpT Outer Membrane Proteases of Enterohemorrhagic and Enteropathogenic Escherichia coli Contribute Differently to the Degradation of Human LL-37

2011 ◽  
Vol 80 (2) ◽  
pp. 483-492 ◽  
Author(s):  
Jenny-Lee Thomassin ◽  
John R. Brannon ◽  
Bernard F. Gibbs ◽  
Samantha Gruenheid ◽  
Hervé Le Moual
Keyword(s):  
Escherichia Coli ◽  
Outer Membrane ◽  
Time Course ◽  
Dependent Manner ◽  
Content Type ◽  
Reading Frame ◽  
E Coli ◽  
Food Borne ◽  
Mutant Strains

ABSTRACTEnterohemorrhagicEscherichia coli(EHEC) and enteropathogenicE. coli(EPEC) are food-borne pathogens that cause serious diarrheal diseases. To colonize the human intestine, these pathogens must overcome innate immune defenses such as antimicrobial peptides (AMPs). Bacterial pathogens have evolved various mechanisms to resist killing by AMPs, including proteolytic degradation of AMPs. To examine the ability of the EHEC and EPEC OmpT outer membrane (OM) proteases to degrade α-helical AMPs,ompTdeletion mutants were generated. Determination of MICs of various AMPs revealed that both mutant strains are more susceptible than their wild-type counterparts to α-helical AMPs, although to different extents. Time course assays monitoring the degradation of LL-37 and C18G showed that EHEC cells degraded both AMPs faster than EPEC cells in an OmpT-dependent manner. Mass spectrometry analyses of proteolytic fragments showed that EHEC OmpT cleaves LL-37 at dibasic sites. The superior protection provided by EHEC OmpT compared to EPEC OmpT against α-helical AMPs was due to higher expression of theompTgene and, in turn, higher levels of the OmpT protein in EHEC. Fusion of the EPECompTpromoter to the EHECompTopen reading frame resulted in decreased OmpT expression, indicating that transcriptional regulation ofompTis different in EHEC and EPEC. We hypothesize that the different contributions of EHEC and EPEC OmpT to the degradation and inactivation of LL-37 may be due to their adaptation to their respective niches within the host, the colon and small intestine, respectively, where the environmental cues and abundance of AMPs are different.

scholarly journals The RipA and RipB Peptidoglycan Endopeptidases Are Individually Nonessential to Mycobacterium smegmatis

2016 ◽  
Vol 198 (9) ◽  
pp. 1464-1475 ◽  
Author(s):  
Daniel J. Martinelli ◽  
Martin S. Pavelka
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Cell Division ◽  
Mycobacterium Smegmatis ◽  
Wild Type ◽  
Content Type ◽  
Deletion Mutations ◽  
Levels Of Detail ◽  
Mutant Strains ◽  
Single Deletion ◽  
Increased Susceptibility

ABSTRACTMycobacteria possess a series of Rip peptidoglycan endopeptidases that have been characterized in various levels of detail. The RipA and RipB proteins have been extensively studied and aredl-endopeptidases, and RipA has been considered essential toMycobacterium smegmatisandMycobacterium tuberculosis. We show here that theripAandripBgenes are individually dispensable inM. smegmatisand that at least one of the genes must be expressed for viability. We characterized strains carrying in-frame deletion mutations ofripAandripBand found that both mutant strains exhibited increased susceptibility to a limited number of antibiotics and to detergent but that only the ΔripAmutant displayed hypersusceptibility to lysozyme. We also constructed and characterized ΔripDand ΔripAΔripDmutants and found that the single mutant had only an intermediate lysozyme hypersusceptibility phenotype compared to that of wild-type cells while loss ofripDin the ΔripAbackground partially rescued the antibiotic and lysozyme phenotypes of the ΔripAmutant.IMPORTANCEWe show that the RipA endopeptidase, which has been considered essential for cell division in certain mycobacteria, is not essential but that at least it or a similar protein, RipB, must be expressed by the bacteria for viability. This work is the first description of strains carrying single deletion mutations of RipA, RipB, and a novel endopeptidase-like protein, RipD.

scholarly journals Inactivation of Lytic Transglycosylases Increases Susceptibility to Aminoglycosides and Macrolides by Altering the Outer Membrane Permeability of Stenotrophomonas maltophilia

2016 ◽  
Vol 60 (5) ◽  
pp. 3236-3239 ◽  
Author(s):  
Chao-Jung Wu ◽  
Yi-Wei Huang ◽  
Yi-Tsung Lin ◽  
Tsuey-Ching Yang
Keyword(s):  
Membrane Permeability ◽  
Outer Membrane ◽  
Stenotrophomonas Maltophilia ◽  
Content Type ◽  
Lytic Transglycosylases ◽  
Qrt Pcr ◽  
Reverse Transcription Pcr ◽  
Underlying Mechanisms ◽  
Outer Membrane Permeability ◽  
Increased Susceptibility

ABSTRACTStenotrophomonas maltophiliaharbors six lytic transglycosylases (LTs):mltA,mltB1,mltB2,mltD1,mltD2, andslt. LT deletion increased susceptibility ofS. maltophiliato aminoglycosides (AGs) and macrolides, and the underlying mechanisms were investigated. The expression of AG-modifying enzymes and efflux pumps was evaluated by quantitative reverse transcription-PCR (qRT-PCR). Susceptibility to 1-N-phenylnaphthylamine, vancomycin, SDS, and bile salts was measured to assess outer membrane permeability. In conclusion, increased outer membrane permeability contributes to LT deletion-mediated increase in aminoglycoside and macrolide susceptibility.

scholarly journals New Aspects of RpoE in Uropathogenic Proteus mirabilis

2014 ◽  
Vol 83 (3) ◽  
pp. 966-977 ◽  
Author(s):  
Ming-Che Liu ◽  
Kuan-Ting Kuo ◽  
Hsiung-Fei Chien ◽  
Yi-Lin Tsai ◽  
Shwu-Jen Liaw
Keyword(s):  
Urinary Tract ◽  
Virulence Factors ◽  
Stress Responses ◽  
Proteus Mirabilis ◽  
Immune Cell ◽  
Polymyxin B ◽  
Urothelial Cells ◽  
Cationic Antimicrobial Peptide ◽  
Content Type ◽  
Tract Infections

Proteus mirabilisis a common human pathogen causing recurrent or persistent urinary tract infections (UTIs). The underlying mechanisms forP. mirabilisto establish UTIs are not fully elucidated. In this study, we showed that loss of the sigma factor E (RpoE), mediating extracytoplasmic stress responses, decreased fimbria expression, survival in macrophages, cell invasion, and colonization in mice but increased the interleukin-8 (IL-8) expression of urothelial cells and swarming motility. This is the first study to demonstrate that RpoE modulated expression of MR/P fimbriae by regulatingmrpI, a gene encoding a recombinase controlling the orientation of MR/P fimbria promoter. By real-time reverse transcription-PCR, we found that the IL-8 mRNA amount of urothelial cells was induced significantly by lipopolysaccharides extracted fromrpoEmutant but not from the wild type. These RpoE-associated virulence factors should be coordinately expressed to enhance the fitness ofP. mirabilisin the host, including the avoidance of immune attacks. Accordingly,rpoEmutant-infected mice displayed more immune cell infiltration in bladders and kidneys during early stages of infection, and therpoEmutant had a dramatically impaired ability of colonization. Moreover, it is noteworthy that urea (the major component in urine) and polymyxin B (a cationic antimicrobial peptide) can induce expression ofrpoEby the reporter assay, suggesting that RpoE might be activated in the urinary tract. Altogether, our results indicate that RpoE is important in sensing environmental cues of the urinary tract and subsequently triggering the expression of virulence factors, which are associated with the fitness ofP. mirabilis, to build up a UTI.

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