The expression of nonagglutinating fimbriae and its role inProteus mirabilisadherence to epithelial cells

1997 ◽  
Vol 43 (8) ◽  
pp. 709-717 ◽  
Author(s):  
Douglas L. Tolson ◽  
Blair A. Harrison ◽  
Roger K. Latta ◽  
Kok K. Lee ◽  
Eleonora Altman
Keyword(s):  
Monoclonal Antibodies ◽  
Urinary Tract ◽  
Cell Lines ◽  
Proteus Mirabilis ◽  
Growth Conditions ◽  
Structural Abnormalities ◽  
Uroepithelial Cell ◽  
Uroepithelial Cells ◽  
Tract Infections

Proteus mirabilis is a common causative agent of human urinary tract infections, especially in catheterized patients and in those patients with structural abnormalities of the urinary tract. In addition to the production of hemolysin and urease, fimbriae-mediated adherence to uroepithelial cells and kidney epithelium may be essential for virulence of P. mirabilis. A single P. mirabilis strain is capable of expressing several morphologically distinct fimbrial species, which can each be favoured by specific in vitro growth conditions. The fimbrial species reported to date include mannose-resistant/Proteus-like fimbriae, ambient temperature fimbriae, P. mirabilis fimbriae, and nonagglutinating fimbriae (NAF). Here, using intact bacteria or purified NAF as immunogens, we have generated the first reported NAF-specific monoclonal antibodies (mAbs). Bacteria expressing NAF as their only fimbrial species adhered strongly to a number of cell lines in vitro, including uroepithelial cell lines. Binding of P. mirabilis was markedly reduced following preincubation with NAF-specific mAbs and Fab fragments. The presence of NAF with highly conserved N-terminal sequences on all P. mirabilis strains so far examined, combined with the ability of both anti-NAF mAbs and purified NAF molecules to inhibit P. mirabilis adherence in vitro, suggests that NAF may contribute to the pathogenesis of P. mirabilis.Key words: fimbriae, adherence, monoclonal antibodies, Proteus mirabilis, receptors.

The effect of growth conditions on in vitro adherence, invasion, and NAF expression by Proteus mirabilis 7570

1998 ◽  
Vol 44 (9) ◽  
pp. 896-904 ◽  
Author(s):  
R K Latta ◽  
M J Schur ◽  
D L Tolson ◽  
E Altman
Keyword(s):  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Proteus Mirabilis ◽  
Growth Conditions ◽  
Upper Urinary Tract ◽  
Host Cells ◽  
Common Cause ◽  
The Media ◽  
Tract Infections

Proteus mirabilis is a common cause of upper urinary tract infections. Fimbriae-mediated adherence of this organism to urinary tract epithelium and invasion of host cells are factors thought to be important in its pathogenesis. We have assessed the effect of growth in serum, blood, and urine on the ability of P. mirabilis 7570 to adhere to and invade in vitro the cell line EJ/28, derived from a human urinary tract tumour, and to express nonagglutinating fimbriae (NAF). Proteus mirabilis was capable of adhering to EJ/28 cells to varying degrees depending upon the growth conditions used. It was invasive under all conditions, except when grown in urine, and was found to be particularly so when serum or blood was present in the media. Expression of NAF occurred under all growth conditions examined and was limited only by a decrease in temperature.Key words: adhesion, invasion, nonagglutinating fimbriae, Proteus mirabilis.

scholarly journals Identification of virulence determinants in uropathogenic Proteus mirabilis using signature-tagged mutagenesis

2008 ◽  
Vol 57 (9) ◽  
pp. 1068-1078 ◽  
Author(s):  
Stephanie D. Himpsl ◽  
C. Virginia Lockatell ◽  
J. Richard Hebel ◽  
David E. Johnson ◽  
Harry L. T. Mobley
Keyword(s):  
Urinary Tract ◽  
Mouse Model ◽  
Proteus Mirabilis ◽  
Virulence Determinants ◽  
Indwelling Catheters ◽  
Cba Mice ◽  
Transposon Mutants ◽  
Tract Infections

The Gram-negative bacterium Proteus mirabilis causes urinary tract infections (UTIs) in individuals with long-term indwelling catheters or those with functional or structural abnormalities of the urinary tract. Known virulence factors include urease, haemolysin, fimbriae, flagella, DsbA, a phosphate transporter and genes involved in cell-wall synthesis and metabolism, many of which have been identified using the technique of signature-tagged mutagenesis (STM). To identify additional virulence determinants and to increase the theoretical coverage of the genome, this study generated and assessed 1880 P. mirabilis strain HI4320 mutants using this method. Mutants with disruptions in genes vital for colonization of the CBA mouse model of ascending UTI were identified after performing primary and secondary in vivo screens in approximately 315 CBA mice, primary and secondary in vitro screens in both Luria broth and minimal A medium to eliminate mutants with minor growth deficiencies, and co-challenge competition experiments in approximately 500 CBA mice. After completion of in vivo screening, a total of 217 transposon mutants were attenuated in the CBA mouse model of ascending UTI. Following in vitro screening, this number was reduced to 196 transposon mutants with a probable role in virulence. Co-challenge competition experiments confirmed significant attenuation for 37 of the 93 transposon mutants tested, being outcompeted by wild-type HI4320. Following sequence analysis of the 37 mutants, transposon insertions were identified in genes including the peptidyl-prolyl isomerases surA and ppiA, glycosyltransferase cpsF, biopolymer transport protein exbD, transcriptional regulator nhaR, one putative fimbrial protein, flagellar M-ring protein fliF and hook protein flgE, and multiple metabolic genes.

scholarly journals Assessment of effectiveness and safety of Ibicella lutea extract in the control of experimental Proteus mirabilis urinary tract infection

2010 ◽  
Vol 4 (12) ◽  
pp. 814-821 ◽  
Author(s):  
Vanessa Sosa ◽  
Pablo Zunino
Keyword(s):  
Urinary Tract ◽  
Proteus Mirabilis ◽  
Intestinal Microflora ◽  
Acquired Resistance ◽  
Intestinal Flora ◽  
South American ◽  
New Strategy ◽  
Indigenous Plant ◽  
Tract Infections

Introduction: Proteus mirabilis is an important cause of complicated urinary tract infections (UTI). Like many other microorganisms, P. mirabilis has acquired resistance to many antibiotics. Due to the serious effects associated with uropathogenic P. mirabilis and the problems related to the use of antibiotics, alternative strategies for its control must be developed. Previously, we studied the effect of Ibicella lutea extract, a South American indigenous plant, on in vitro uropathogenicity of P. mirabilis. We observed that I. lutea extract had an effect on various attributes associated with P. mirabilis urovirulence. The objective of this study was to assess I. lutea extract against UTI by P. mirabilis. Methodology: This study was based on the effect of I. lutea extract to prevent or treat P. mirabilis experimental UTI in mice and the influence of this administration on the normal intestinal flora. Also, we studied the toxicity, mutagenicity, and antimutagenicity of the extract. Results: In this study, while I. lutea administration showed an effect in the prevention and treatment of UTI in the mouse, the intestinal microflora did not change. The I. lutea extract was neither toxic nor mutagenic although the extract showed antimutagenic properties. Conclusion: These findings suggest that the administration of I. lutea extract could represent an interesting new strategy to control P. mirabilis UTI.

scholarly journals Catalase Activity is Critical for Proteus mirabilis Biofilm Development, EPS Composition, and Dissemination During Catheter-Associated Urinary Tract Infection

2021 ◽  
Author(s):  
Ashley N. White ◽  
Brian S. Learman ◽  
Aimee L. Brauer ◽  
Chelsie E. Armbruster
Keyword(s):  
Urinary Tract ◽  
Proteus Mirabilis ◽  
Catalase Activity ◽  
Defense Mechanisms ◽  
Extracellular Polymeric Substances ◽  
Key Factor ◽  
Increased Sensitivity ◽  
Tract Infections ◽  
Biofilm Development

Proteus mirabilis is a leading uropathogen of catheter-associated urinary tract infections (CAUTIs), which are among the most common healthcare-associated infections worldwide. A key factor that contributes to P. mirabilis pathogenesis and persistence during CAUTI is the formation of catheter biofilms, which provide increased resistance to antibiotic treatment and host defense mechanisms. Another factor that is important for bacterial persistence during CAUTI is the ability to resist reactive oxygen species (ROS), such as through the action of the catalase enzyme. Potent catalase activity is one of the defining biochemical characteristics of P. mirabilis , and the single catalase gene ( katA ) encoded in strain HI4320 was recently identified as a candidate fitness factor for UTI, CAUTI, and bacteremia. Here we show that disruption of katA results in increased ROS levels, increased sensitivity to peroxide, and decreased biofilm biomass. The biomass defect was due to a decrease in extracellular polymeric substances (EPS) production by the ΔkatA mutant, and specifically due to reduced carbohydrate content. Importantly, the biofilm defect resulted in decreased antibiotic resistance in vitro and a colonization defect during experimental CAUTI. The ΔkatA mutant also exhibited decreased fitness in a bacteremia model, supporting a dual role for catalase in P. mirabilis biofilm development and immune evasion.

Chlorpromazine-impregnated catheters as a potential strategy to control biofilm-associated urinary tract infections

2019 ◽  
Vol 14 (12) ◽  
pp. 1023-1034 ◽  
Author(s):  
José JC Sidrim ◽  
Bruno R Amando ◽  
Francisco IF Gomes ◽  
Marilia SMG do Amaral ◽  
Paulo CP de Sousa ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Klebsiella Pneumoniae ◽  
Urinary Tract Infections ◽  
Proteus Mirabilis ◽  
Biofilm Formation ◽  
Antibiofilm Activity ◽  
Potential Strategy ◽  
Tract Infections

Aim: This study proposes the impregnation of Foley catheters with chlorpromazine (CPZ) to control biofilm formation by Escherichia coli, Proteus mirabilis and Klebsiella pneumoniae. Materials & methods: The minimum inhibitory concentrations (MICs) for CPZ and the effect of CPZ on biofilm formation were assessed. Afterward, biofilm formation and the effect of ciprofloxacin and meropenem (at MIC) on mature biofilms grown on CPZ-impregnated catheters were evaluated. Results: CPZ MIC range was 39.06–625 mg/l. CPZ significantly reduced (p < 0.05) biofilm formation in vitro and on impregnated catheters. In addition, CPZ-impregnation potentiated the antibiofilm activity of ciprofloxacin and meropenem. Conclusion: These findings bring perspectives for the use of CPZ as an adjuvant for preventing and treating catheter-associated urinary tract infections.

scholarly journals An iron-regulated outer-membrane protein of Proteus mirabilis is a haem receptor that plays an important role in urinary tract infection and in in vivo growth

2007 ◽  
Vol 56 (12) ◽  
pp. 1600-1607 ◽  
Author(s):  
Analía Lima ◽  
Pablo Zunino ◽  
Bruno D'Alessandro ◽  
Claudia Piccini
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Outer Membrane ◽  
Proteus Mirabilis ◽  
Outer Membrane Proteins ◽  
Mammalian Host ◽  
Tract Infections

Proteus mirabilis, a common cause of urinary tract infections, expresses iron-regulated outer-membrane proteins (OMPs) in response to iron restriction. It has been suggested that a 64 kDa OMP is involved in haemoprotein uptake and that this might have a role in pathogenesis. In order to confirm this hypothesis, this study generated a P. mirabilis mutant strain (P7) that did not express the 64 kDa OMP, by insertion of the TnphoA transposon. The nucleotide sequence of the interrupted gene revealed that it corresponded to a haemin receptor precursor. Moreover, in vitro growth assays showed that the mutant was unable to grow using haemoglobin and haemin as unique iron sources. The authors also carried out in vivo growth and infectivity assays and demonstrated that P7 was not able to survive in an in vivo model and was less efficient than wild-type strain Pr 6515 in colonizing the urinary tract. These results confirmed that the P. mirabilis 64 kDa iron-regulated OMP is a haem receptor that has an important role for survival and multiplication of these bacteria in the mammalian host and in the development of urinary tract infection.

Effect of antibiotic treatment on receptivity of uroepithelial ceils to uropathogens

1988 ◽  
Vol 34 (3) ◽  
pp. 327-331 ◽  
Author(s):  
Gregor Reid ◽  
Andrew W. Bruce ◽  
Mojtaba Beheshti
Keyword(s):  
Urinary Tract ◽  
Antibiotic Treatment ◽  
Term Treatment ◽  
Short Term Treatment ◽  
History Of ◽  
Uroepithelial Cells ◽  
Tract Infections ◽  
Group 1

The management of female patients with recurrent urinary tract infections still remains a problem, and long-term prophylactic or short intermittent courses of antibiotics are the standard forms of therapy. In this report, 10 patients were examined for the effects of long- and short-term treatment with trimethoprim–sulfamethoxazole (TMP–SMX) antibiotics on the receptivity of uroepithelial cells to bacterial adherence. The urine of all patients was sterile while on antibiotic therapy. Few bacteria were found adherent to the cells from adult patients (group 1, mean age 36 years) on long-term antibiotics, but the cells were highly receptive to uropathogens in vitro, especially for Escherichia coli expressing mannose-resistant adhesins. Controls of age-matched adult females were included and in vitro adherence levels were found to be higher for those women with a history of urinary tract infection compared with those with no past record of infection. In the second group, elderly patients (mean age 87 years) presented with bacteriuria, and their uroepithelial cells were found to be colonized by uropathogens to a significantly greater extent than their controls. The adherent population was reduced during 7-day TMP–SMX antibiotic treatment, but increased posttherapy, particularly in two patients who subsequently became reinfected. The in vitro results showed that uroepithelial cells retain their receptivity to uropathogenic adherence, both during and after treatment. Although antibiotics eradicate uropathogens from the urinary tract, patients remain susceptible to recolonization by uropathogens and are at risk of reinfection after completion of therapy.

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.

Proteus mirabilis fimbriae (PMF) are important for both bladder and kidney colonization in mice

Microbiology ◽  
2003 ◽  
Vol 149 (11) ◽  
pp. 3231-3237 ◽  
Author(s):  
Pablo Zunino ◽  
Vanessa Sosa ◽  
Andrew G. Allen ◽  
Andrew Preston ◽  
Geraldine Schlapp ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Proteus Mirabilis ◽  
Bacterial Colonization ◽  
Infection Models ◽  
Uroepithelial Cells ◽  
Different Origins ◽  
Different Sources ◽  
Lower Urinary

Proteus mirabilis expresses different types of fimbriae simultaneously. Several fimbrial types have been described and their role in the colonization of the urinary tract is under study. Previously, P. mirabilis fimbriae (PMF) have been shown to be associated with bacterial colonization of the lower urinary tract but not of the kidneys. In this study, a pmfA mutant was generated and used in several in vivo and in vitro studies. Two different urinary tract infection models in the mouse and two in vitro assays of bacterial adhesion to uroepithelial cells were performed. Expression of PmfA in a collection of P. mirabilis strains of different sources was also assessed. The results shown here indicate that PMF are involved in both bladder and kidney colonization by P. mirabilis and that these fimbriae are widely distributed among P. mirabilis isolates from different origins since all strains tested expressed PmfA.

scholarly journals A small-molecular inhibitor against Proteus mirabilis urease to treat catheter-associated urinary tract infections

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Scarlet Milo ◽  
Rachel A. Heylen ◽  
John Glancy ◽  
George T. Williams ◽  
Bethany L. Patenall ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Proteus Mirabilis ◽  
Bacterial Infections ◽  
Competitive Inhibition ◽  
Enzyme Inhibitor ◽  
Urinary Catheters ◽  
Design Synthesis ◽  
In Silico Docking ◽  
Tract Infections

AbstractInfection and blockage of indwelling urinary catheters is significant owing to its high incidence rate and severe medical consequences. Bacterial enzymes are employed as targets for small molecular intervention in human bacterial infections. Urease is a metalloenzyme known to play a crucial role in the pathogenesis and virulence of catheter-associated Proteus mirabilis infection. Targeting urease as a therapeutic candidate facilitates the disarming of bacterial virulence without affecting bacterial fitness, thereby limiting the selective pressure placed on the invading population and lowering the rate at which it will acquire resistance. We describe the design, synthesis, and in vitro evaluation of the small molecular enzyme inhibitor 2-mercaptoacetamide (2-MA), which can prevent encrustation and blockage of urinary catheters in a physiologically representative in vitro model of the catheterized urinary tract. 2-MA is a structural analogue of urea, showing promising competitive activity against urease. In silico docking experiments demonstrated 2-MA’s competitive inhibition, whilst further quantum level modelling suggests two possible binding mechanisms.

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