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.

scholarly journals The Repeat-In-Toxin Family Member TosA Mediates Adherence of Uropathogenic Escherichia coli and Survival during Bacteremia

2011 ◽  
Vol 80 (2) ◽  
pp. 493-505 ◽  
Author(s):  
Patrick D. Vigil ◽  
Travis J. Wiles ◽  
Michael D. Engstrom ◽  
Lev Prasov ◽  
Matthew A. Mulvey ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Virulence Factors ◽  
Upper Urinary Tract ◽  
Host Cells ◽  
Content Type ◽  
E Coli ◽  
Wide Range ◽  
Novel Target ◽  
Tract Infections

ABSTRACTUropathogenicEscherichia coli(UPEC) is responsible for the majority of uncomplicated urinary tract infections (UTI) and represents the most common bacterial infection in adults. UPEC utilizes a wide range of virulence factors to colonize the host, including the novel repeat-in-toxin (RTX) protein TosA, which is specifically expressed in the host urinary tract and contributes significantly to the virulence and survival of UPEC.tosA, found in strains within the B2 phylogenetic subgroup ofE. coli, serves as a marker for strains that also contain a large number of well-characterized UPEC virulence factors. The presence oftosAin anE. coliisolate predicts successful colonization of the murine model of ascending UTI, regardless of the source of the isolate. Here, a detailed analysis of the function oftosArevealed that this gene is transcriptionally linked to genes encoding a conserved type 1 secretion system similar to other RTX family members. TosA localized to the cell surface and was found to mediate (i) adherence to host cells derived from the upper urinary tract and (ii) survival in disseminated infections and (iii) to enhance lethality during sepsis (as assessed in two different animal models of infection). An experimental vaccine, using purified TosA, protected vaccinated animals against urosepsis. From this work, it was concluded that TosA belongs to a novel group of RTX proteins that mediate adherence and host damage during UTI and urosepsis and could be a novel target for the development of therapeutics to treat ascending UTIs.

scholarly journals Relative Fecal Abundance of Extended-Spectrum-β-Lactamase-Producing Escherichia coli Strains and Their Occurrence in Urinary Tract Infections in Women

2013 ◽  
Vol 57 (9) ◽  
pp. 4512-4517 ◽  
Author(s):  
Etienne Ruppé ◽  
Brandusa Lixandru ◽  
Radu Cojocaru ◽  
Çağrı Büke ◽  
Elisabeth Paramythiotou ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Virulence Factors ◽  
Urinary Tract Infections ◽  
Predictive Values ◽  
Content Type ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
Extended Spectrum ◽  
Tract Infections

ABSTRACTExtended-spectrum-beta-lactamase (ESBL)-producingEscherichia coli(ESBLE. coli) strains are of major concern because few antibiotics remain active against these bacteria. We investigated the association between the fecal relative abundance (RA) of ESBL-producingE. coli(ESBL-RA) and the occurrence of ESBLE. coliurinary tract infections (UTIs). The first stool samples passed after suspicion of UTI from 310 women with subsequently confirmedE. coliUTIs were sampled and tested for ESBL-RA by culture on selective agar. Predictive values of ESBL-RA for ESBLE. coliUTI were analyzed for women who were not exposed to antibiotics when the stool was passed. ESBLE. coliisolates were characterized for ESBL type, phylogroup, relatedness, and virulence factors. The prevalence of ESBLE. colifecal carriage was 20.3%, with ESBLE. coliUTIs being present in 12.3% of the women. The mean ESBL-RA (95% confidence interval [CI]) was 13-fold higher in women exposed to antibiotics at the time of sampling than in those not exposed (14.3% [range, 5.6% to 36.9%] versus 1.1% [range, 0.32% to 3.6%], respectively;P< 0.001) and 18-fold higher in women with ESBLE. coliUTI than in those with anotherE. coliUTI (10.0% [range, 0.54% to 100%] versus 0.56% [range, 0.15% to 2.1%[, respectively;P< 0.05). An ESBL-RA of <0.1% was 100% predictive of a non-ESBLE. coliUTI. ESBL type, phylogroup, relatedness, and virulence factors were not found to be associated with ESBL-RA. In conclusion, ESBL-RA was linked to the occurrence of ESBLE. coliUTI in women who were not exposed to antibiotics and who had the same clone ofE. coliin urine samples and fecal samples. Especially, a low ESBL-RA appeared to be associated with a low risk of ESBLE. coliinfection.

scholarly journals Transcriptome of Proteus mirabilis in the Murine Urinary Tract: Virulence and Nitrogen Assimilation Gene Expression

2011 ◽  
Vol 79 (7) ◽  
pp. 2619-2631 ◽  
Author(s):  
Melanie M. Pearson ◽  
Alejandra Yep ◽  
Sara N. Smith ◽  
Harry L. T. Mobley
Keyword(s):  
Gene Expression ◽  
Urinary Tract ◽  
Glutamate Dehydrogenase ◽  
Proteus Mirabilis ◽  
Transcriptional Analysis ◽  
Broth Culture ◽  
Pathogenic Potential ◽  
Content Type ◽  
Tract Infections

ABSTRACTThe enteric bacteriumProteus mirabilisis a common cause of complicated urinary tract infections. In this study, microarrays were used to analyzeP. mirabilisgene expressionin vivofrom experimentally infected mice. Urine was collected at 1, 3, and 7 days postinfection, and RNA was isolated from bacteria in the urine for transcriptional analysis. Across nine microarrays, 471 genes were upregulated and 82 were downregulatedin vivocompared toin vitrobroth culture. Genes upregulatedin vivoencoded mannose-resistantProteus-like (MR/P) fimbriae, urease, iron uptake systems, amino acid and peptide transporters, pyruvate metabolism enzymes, and a portion of the tricarboxylic acid (TCA) cycle enzymes. Flagella were downregulated. Ammonia assimilation geneglnA(glutamine synthetase) was repressedin vivo, whilegdhA(glutamate dehydrogenase) was upregulatedin vivo. Contrary to our expectations, ammonia availability due to urease activity inP. mirabilisdid not drive this gene expression. AgdhAmutant was growth deficient in minimal medium with citrate as the sole carbon source, and loss ofgdhAresulted in a significant fitness defect in the mouse model of urinary tract infection. UnlikeEscherichia coli, which repressesgdhAand upregulatesglnAin vivoand cannot utilize citrate, the data suggest thatP. mirabilisuses glutamate dehydrogenase to monitor carbon-nitrogen balance, and this ability contributes to the pathogenic potential ofP. mirabilisin the urinary tract.

scholarly journals A Conserved PapB Family Member, TosR, Regulates Expression of the Uropathogenic Escherichia coli RTX Nonfimbrial Adhesin TosA while Conserved LuxR Family Members TosE and TosF Suppress Motility

2014 ◽  
Vol 82 (9) ◽  
pp. 3644-3656 ◽  
Author(s):  
Michael D. Engstrom ◽  
Christopher J. Alteri ◽  
Harry L. T. Mobley
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Virulence Factors ◽  
Upper Urinary Tract ◽  
Host Cells ◽  
Promoter Regions ◽  
Content Type ◽  
Tract Infections

ABSTRACTA heterogeneous subset of extraintestinal pathogenicEscherichia coli(ExPEC) strains, referred to as uropathogenicE. coli(UPEC), causes most uncomplicated urinary tract infections. However, no core set of virulence factors exists among UPEC strains. Instead, the focus of the analysis of urovirulence has shifted to studying broad classes of virulence factors and the interactions between them. For example, the RTX nonfimbrial adhesin TosA mediates adherence to host cells derived from the upper urinary tract. The associatedtosoperon is well expressedin vivobut poorly expressedin vitroand encodes TosCBD, a predicted type 1 secretion system. TosR and TosEF are PapB and LuxR family transcription factors, respectively; however, no role has been assigned to these potential regulators. Thus, the focus of this study was to determine how TosR and TosEF regulatetosAand affect the reciprocal expression of adhesins and flagella. Among a collection of sequenced UPEC strains, 32% (101/317) were found to encode TosA, and nearly all strains (91% [92/101]) simultaneously carried the putative regulatory genes. Deletion oftosRalleviatestosArepression. Thetospromoter was localized upstream oftosRusing transcriptional fusions of putative promoter regions withlacZ. TosR binds to this region, affecting a gel shift. A 100-bp fragment 220 to 319 bp upstream oftosRinhibits binding, suggesting localization of the TosR binding site. TosEF, on the other hand, downmodulate motility when overexpressed by preventing the expression offliC, encoding flagellin. Deletion oftosEFincreased motility. Thus, we present an additional example of the reciprocal control of adherence and motility.

scholarly journals Complete Genome Sequence of Proteus mirabilis Phage Myduc

2019 ◽  
Vol 8 (47) ◽  
Author(s):  
Jennifer Tran ◽  
Lauren Lessor ◽  
Chandler O’Leary ◽  
Jason Gill ◽  
Mei Liu
Keyword(s):  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Genome Sequence ◽  
Proteus Mirabilis ◽  
Complete Genome Sequence ◽  
Complete Genome ◽  
Nosocomial Pathogen ◽  
Content Type ◽  
Small Genome ◽  
Tract Infections

Proteus mirabilis as a nosocomial pathogen is often the cause of urinary tract infections. This announcement describes the complete genome sequence of a P. mirabilis myophage named Myduc. Phage Myduc is related to Enterobacteria phage phiEcoM-GJ1, which belongs to a group of myophages with small genome sizes (52,000 to 56,000 bp) possessing a T7-like RNA polymerase.

scholarly journals Proteus mirabilis isolates of different origins do not show correlation with virulence attributes and can colonize the urinary tract of mice

Microbiology ◽  
2006 ◽  
Vol 152 (7) ◽  
pp. 2149-2157 ◽  
Author(s):  
Vanessa Sosa ◽  
Geraldine Schlapp ◽  
Pablo Zunino
Keyword(s):  
Urinary Tract ◽  
Virulence Factors ◽  
Proteus Mirabilis ◽  
Protein Patterns ◽  
Wide Range ◽  
Urease Production ◽  
Tract Infections ◽  
Different Origins

Proteus mirabilis has been described as an aetiological agent in a wide range of infections, playing an important role in urinary tract infections (UTIs). In this study, a collection of P. mirabilis isolates obtained from clinical and non-clinical sources was analysed in order to determine a possible correlation between origin, virulence factors and in vivo infectivity. Isolates were characterized in vitro, assessing several virulence properties that had been previously associated with P. mirabilis uropathogenicity. Swarming motility, urease production, growth in urine, outer-membrane protein patterns, ability to grow in the presence of different iron sources, haemolysin and haemagglutinin production, and the presence and expression of diverse fimbrial genes, were analysed. In order to evaluate the infectivity of the different isolates, the experimental ascending UTI model in mice was used. Additionally, the Dienes test and the enterobacterial repetitive intergenic consensus (ERIC)-PCR assay were performed to assess the genetic diversity of the isolates. The results of the present study did not show any correlation between distribution of the diverse potential urovirulence factors and isolate source. No significant correlation was observed between infectivity and the origin of the isolates, since they all similarly colonized the urinary tract of the challenged mice. Finally, all isolates showed unique ERIC-PCR patterns, indicating that the isolates were genetically diverse. The results obtained in this study suggest that the source of P. mirabilis strains cannot be correlated with pathogenic attributes, and that the distribution of virulence factors between isolates of different origins may correspond to the opportunistic nature of the organism.

scholarly journals Complete Genome Sequence of Proteus mirabilis Siphophage Saba

2019 ◽  
Vol 8 (41) ◽  
Author(s):  
James Nguyen ◽  
Laith Harb ◽  
Russell Moreland ◽  
Mei Liu ◽  
Jason J. Gill ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Proteus Mirabilis ◽  
Genome Annotation ◽  
Complete Genome ◽  
Enteric Bacterium ◽  
Gram Negative ◽  
Content Type ◽  
Protein Levels ◽  
Tract Infections

Proteus mirabilis is a Gram-negative enteric bacterium associated with complicated human urinary tract infections. Here, we present the complete genome annotation for P. mirabilis siphophage Saba. With a 60,056-bp genome and 75 predicted genes, Saba is most similar at the nucleotide and protein levels to phage Chi and Chi-like viruses.

scholarly journals Derepression of the smvA Efflux System Arises in Clinical Isolates of Proteus mirabilis and Reduces Susceptibility to Chlorhexidine and Other Biocides

2019 ◽  
Vol 63 (12) ◽  
Author(s):  
H. Pelling ◽  
L. J. Bock ◽  
J. Nzakizwanayo ◽  
M. E. Wand ◽  
E. L. Denham ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Proteus Mirabilis ◽  
Polymyxin B ◽  
Clinical Isolates ◽  
Efflux System ◽  
Content Type ◽  
Common Pathogen

ABSTRACT Proteus mirabilis is a common pathogen of the catheterized urinary tract and often described as intrinsically resistant to the biocide chlorhexidine (CHD). Here, we demonstrate that derepression of the smvA efflux system has occurred in clinical isolates of P. mirabilis and reduces susceptibility to CHD and other cationic biocides. Compared with other isolates examined, P. mirabilis RS47 exhibited a significantly higher CHD MIC (≥512 μg/ml) and significantly greater expression of smvA. Comparison of the RS47 smvA and cognate smvR repressor with sequences from other isolates indicated that RS47 carries an inactivated smvR. Complementation of RS47 with a functional smvR from isolate RS50a (which exhibited the lowest smvA expression and lowest CHD MIC) reduced smvA expression by ∼59-fold and markedly lowered the MIC of CHD and other cationic biocides. Although complementation of RS47 did not reduce MICs to concentrations observed in isolate RS50a, the significantly lower polymyxin B MIC of RS50a indicated that differences in lipopolysaccharide (LPS) structure are also a factor in P. mirabilis CHD susceptibility. To determine if exposure to CHD can select for mutations in smvR, clinical isolates with the lowest CHD MICs were adapted to grow at increasing concentrations of CHD up to 512 μg/ml. Analysis of the smvR in adapted populations indicated that mutations predicted to inactivate smvR occurred following CHD exposure in some isolates. Collectively, our data show that smvA derepression contributes to reduced biocide susceptibility in P. mirabilis, but differences in LPS structure between strains are also likely to be an important factor.

scholarly journals Presence of Putative Repeat-in-Toxin Gene tosA in Escherichia coli Predicts Successful Colonization of the Urinary Tract

mBio ◽  
2011 ◽  
Vol 2 (3) ◽  
Author(s):  
Patrick D. Vigil ◽  
Ann E. Stapleton ◽  
James R. Johnson ◽  
Thomas M. Hooton ◽  
Andrew P. Hodges ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Virulence Factors ◽  
Urinary Tract Infections ◽  
Murine Model ◽  
Toxin Gene ◽  
Content Type ◽  
E Coli ◽  
Tract Infections ◽  
Successful Colonization

ABSTRACTUropathogenicEscherichia coli(UPEC) strains, which cause the majority of uncomplicated urinary tract infections (UTIs), carry a unique assortment of virulence or fitness genes. However, no single defining set of virulence or fitness genes has been found in all strains of UPEC, making the differentiation between UPEC and fecal commensal strains ofE. colidifficult without the use of animal models of infection or phylogenetic grouping. In the present study, we consider three broad categories of virulence factors simultaneously to better define a combination of virulence factors that predicts success in the urinary tract. A total of 314 strains ofE. coli, representing isolates from fecal samples, asymptomatic bacteriuria, complicated UTIs, and uncomplicated bladder and kidney infections, were assessed by multiplex PCR for the presence of 15 virulence or fitness genes encoding adhesins, toxins, and iron acquisition systems. The results confirm previous reports of gene prevalence among isolates from different clinical settings and identify several new patterns of gene associations. One gene,tosA, a putative repeat-in-toxin (RTX) homolog, is present in 11% of fecal strains but 25% of urinary isolates. WhereastosA-positive strains carry an unusually high number (11.2) of the 15 virulence or fitness genes,tosA-negative strains have an average of only 5.4 virulence or fitness genes. The presence oftosAwas predictive of successful colonization of a murine model of infection, even among fecal isolates, and can be used as a marker of pathogenic strains of UPEC within a distinct subset of the B2 lineage.IMPORTANCEEscherichia coliis the primary cause of urinary tract infections, the most common bacterial infection of humans. Virulence of a uropathogenic strain is typically defined by the clinical source of the isolate, the ability to colonize the bladder and kidneys in a murine model, the phylogenetic group of the bacterium, and virulence gene content. Here we describe a novel single gene, the repeat-in-toxin genetosA, the presence of which predicts virulence ofE. coliisolates regardless of source. Rapid identification of uropathogenic strains ofE. colimay aid in the development of therapeutic and preventive therapies.

scholarly journals Draft Genomic Sequence of Escherichia coli Sequence Type 131, Isolated from Retail Chicken Skin

2019 ◽  
Vol 8 (7) ◽  
Author(s):  
Aixia Xu ◽  
William Mackay ◽  
O. Joseph Scullen ◽  
Shiowshuh Sheen ◽  
Rommel Ramos ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Urinary Tract ◽  
Virulence Factors ◽  
Genomic Sequence ◽  
Foodborne Pathogen ◽  
Sequence Type ◽  
Content Type ◽  
Chicken Skin ◽  
Tract Infections

Escherichia coli sequence type 131 (ST131) is a foodborne pathogen increasingly associated with urinary tract infections. We report here the draft genomic sequence of ST131 B7S75, isolated from retail chicken skin, including information about its virulence factors and antibiotic resistance.

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