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 ◽  
...  

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.

Microbiology ◽  
2006 ◽  
Vol 152 (7) ◽  
pp. 2149-2157 ◽  
Author(s):  
Vanessa Sosa ◽  
Geraldine Schlapp ◽  
Pablo Zunino

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.


1997 ◽  
Vol 43 (8) ◽  
pp. 709-717 ◽  
Author(s):  
Douglas L. Tolson ◽  
Blair A. Harrison ◽  
Roger K. Latta ◽  
Kok K. Lee ◽  
Eleonora Altman

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.


2004 ◽  
Vol 72 (4) ◽  
pp. 2445-2448 ◽  
Author(s):  
James R. Johnson ◽  
Connie Clabots ◽  
Helmut Hirt ◽  
Christopher Waters ◽  
Gary Dunny

ABSTRACT Isogenic Enterococcus faecalis strains that differ in their expression of aggregation substance (AS) and its cognate receptor, enterococcal binding substance (EBS), were compared for urovirulence in mice. Strain OG1SSp/pCF500 (inducible AS+, constitutive EBS+) failed to outcompete isogenic derivative INY3000 (AS− EBS−) in the urine, bladders, or kidneys of mice harvested at 48 h postinoculation. Neither mouse nor human urine induced AS expression by OG1SSp/pCF500. Recombinant strain OG1SSp/pINY1801 (constitutive AS+, EBS+) exhibited plasmid segregation that was as extensive in vivo as in vitro. These data suggest that AS and EBS do not contribute to upper or lower urinary tract colonization by E. faecalis and that growth in urine does not induce AS expression by strains carrying plasmids in the pCF10 family.


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

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.


2008 ◽  
Vol 580 (3) ◽  
pp. 394-400 ◽  
Author(s):  
Masashi Ukai ◽  
Hironori Yuyama ◽  
Akira Fujimori ◽  
Akiko Koakutsu ◽  
Masanao Sanagi ◽  
...  

2007 ◽  
Vol 56 (12) ◽  
pp. 1600-1607 ◽  
Author(s):  
Analía Lima ◽  
Pablo Zunino ◽  
Bruno D'Alessandro ◽  
Claudia Piccini

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.


2014 ◽  
Vol 8 (7-8) ◽  
pp. 524 ◽  
Author(s):  
Christos Komninos ◽  
Iraklis Mitsogiannis

Benign prostatic hyperplasia (BPH) is considered a frequent cause of bladder outlet obstruction (BOO) and lower urinary tract symptoms. This review addresses the bladder response to BOO and focuses on the alterations and biochemical adaptability of the bladder wall in the presence of hypoxia. A literature review of published articles has been performed, including both in vivo and in vitro studies on human and animal tissue.


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