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PubMed1996

Uptake pathways of clinical isolates of Proteus mirabilis into human epithelial cell lines.

Proteus mirabilis isolates obtained from urine and faeces showed high invasion levels into several human epithelial cell lines in gentamicin assays. Invasion efficiencies of isolate 102 from a monkey with diarrhoea equalled or even exceeded those of Salmonella typhi strain Ty2 (6.3 to 13.8% of the inoculum). Vegetative, non-swarming P.mirabilis invaded epithelial cells efficiently and were found in endosomes and free in the cytoplasm. Although inhibition of eukaryotic protein synthesis by cycloheximide did not reduce bacterial uptake, inhibition with bacteriostatic antibiotics of bacterial protein-, RNA-, or DNA-synthesis reduced invasion drastically. Involvement of eukaryotic structures and processes in internalization was determined by using various inhibitors in the invasion assay. Uptake of P.mirabilis isolated from urine into gut (INT 407, HCT-8) cells and bladder (T24) cells was dramatically inhibited only by microfilament depolymerization. Internalization of faecal isolate 102 into gut or bladder epithelial cells was inhibited by depolymerization of microfilaments or microtubules. Engulfment of isolate 102 into T24 bladder cells was also reduced by inhibition of receptor-mediated endocytosis. Interference with endosome acidification decreased the number of intracellular bacteria of isolate 102 in all three cell lines. These results suggest that P.mirabilis isolates from different sources are internalized by epithelial cells by different eukaryotic processes, and that these processes can vary between cell lines.

Actin Cytoskeleton↗
PubMed1996

Defined mutants of Proteus mirabilis lacking flagella cause ascending urinary tract infection in mice.

A clinical isolate of Proteus mirabilis (Pr 990) and an isogenic non-flagellate allelic replacement mutant (Pr M9) were tested for their ability to cause infection in the ascending mouse model of urinary tract infection. Wild-type Pr 990 differentiates into swarmer cells in brain-heart infusion broth. Pr M9 neither has flagella nor does it apparently differentiate into swarmer cells after subculturing. The infectivity of both strains from an initial culture and the sixth subculture was assessed in the ascending urinary tract infection mouse model. Infection was ascertained by determining colony forming units from kidney and bladder homogenates from individual mice 7 days after inoculation. In all cases the nonflagellate mutant Pr M9 was at least as infective as Pr 990. Using bacteria from the first culture, Pr M9 infected 61.5% and Pr 990 infected 45.5% of mice tested. The levels of viable counts were similar between the Pr M9 and the Pr 990 infections. Using bacteria from the sixth subculture, Pr M9 infected 75% and Pr 990 infected 76.5% of mice tested. Again viable counts were similar. Pr 990 increased in infectivity from the first to the sixth subculture, whereas Pr M9 did not, but this may be a reflection of the high initial rate of infectivity with first culture Pr M9. These results suggest that neither flagella nor swarmer cells are required for P. mirabilis infectivity in ascending urinary tract infections in mice.

Alleles↗
PubMed1986

Urinary pathogenicity of Proteus mirabilis strains isolated from faeces or urine.

Urinary and faecal isolates of Proteus mirabilis were studied with respect to a number of bacterial properties as possible virulence factors in the pathogenesis of urinary tract infections: experimental virulence in a mouse model, haemolysin production, haemagglutinating properties, hydrophobicity of the bacterial surface, sensitivity to the bactericidal effect of human serum, serotype and cell invasiveness. Urinary isolates were slightly more virulent than faecal isolates in the mouse model. No other significant differences were found between both groups. So urinary strains seem to be selected from the faecal reservoir mainly on the basis of their prevalence in the faeces and not on the basis of the possession of particular virulence factors.

Animals↗
PubMed1978

Serotyping in epidemiological tracing of nosocomially acquired Proteus mirabilis in a geriatric ward.

Samples taken from patients, staff, and hospital milieu at intervals of two weeks for 41 weeks were analysed for nosocomial spread of Proteus mirabilis. Eighty-eight per cent of 3,519 colonies were serotyped into 21 0 groups. By O grouping and H typing, nosocomial spread of P. mirabilis could be demonstrated in several cases between patients in the same room. No spread between rooms was found. The acquisition of P. mirabilis between patients probably occurred as the result of cross-infection due to inadequate nursing technique.

Aged↗
PubMedDate not supplied

Cryoglobulinaemia in a patient with Proteus mirabilis sepsis.

Mixed polyclonal cryoglobulinaemia was evidenced in a 49-year-old woman admitted to our hospital because of Proteus mirabilis sepsis associated with polyarthralgia and purpuric manifestations on the lower limbs. Cryoglobulins and circulating immune complexes decreased during the second week of illness and disappeared after recovery. CH50, C3 and properdin factor B, which were low during the early phase of the illness, returned to normal; C4 was normal throughout. The rapid clearance of cryoglobulins and immune complexes and the restoration of a normal complement profile might all be explained by the gradual elimination of P. mirabilis due to chemotherapeutic treatment.

Complement C3↗
PubMed1982

Interaction of mezlocillin and cefoxitin against Proteus morganii in the granuloma pouch model.

The interaction of cefoxitin and mezlocillin was studied in rats using the granuloma pouch technique. Proteus morganii strains against which cefoxitin and penicillins exhibited antagonistic antibacterial activity were selected for infection of the pouches. Animals were treated with cefoxitin and/or mezlocillin, and bacterial counts, drug levels and beta-lactamase production in the pouch exudate monitored. A significant decrease in bacterial counts was seen after administration of mezlocillin and cefoxitin in combination but not after the drugs administered alone. Drug concentrations of mezlocillin and/or cefoxitin corresponded directly to the rate of induction of beta-lactamase activity. Although both beta-lactam antibiotics induce beta-lactamase activity, administered in combination in vivo they appear to protect each other from being inactivated thus resulting in synergistic antibacterial activity.

Animals↗
PubMed1987

Comparative activities of five antimicrobial agents in experimental Proteus pyelonephritis in mice.

Five antimicrobial agents, ciprofloxacin, ticarcillin, piperacillin, aztreonam and gentamicin, were compared both in vitro (MIC's, time-kill studies) and in vivo, in the treatment of experimental Proteus mirabilis pyelonephritis in mice. In the treatment of the pyelonephritis, ciprofloxacin was clearly superior to the other agents, both with respect to the percentage of sterile kidneys after treatment as with respect to the mean numbers of bacteria per kidney. The results can only be partially explained by the in vitro activities of the different antibiotics.

Animals↗
PubMed1998

Antibiotic sensitivity and proticine typing of Proteus mirabilis strains associated with rheumatoid arthritis.

Urinary isolates of Proteus mirabilis, obtained from 49 RA patients and 44 healthy controls, were tested for susceptibility to antibiotics by the disc diffusion method. In addition, P. mirabilis isolates were also tested for proticine production and sensitivity (p/s) typing by the inhibition of growth of each test isolate against 13 reference strains of P. mirabilis. The P. mirabilis isolates from both RA patients and healthy controls were highly susceptible to norfloxacin, ciprofloxacin and trimethoprim, but less to minocycline. The urine of RA patients contained fewer different types of P. mirabilis strains than those isolated from healthy controls. All of the strains found in the RA patients were proticine producers (P < 0.001), mostly of proticine 3 (P < 0.005). The presence of such strains provides evidence of a sub-clinical upper urinary tract infection with P. mirabilis in some RA patients. Therapeutic intervention in RA with relevant antibiotics requires evaluation.

Adult↗
PubMed2007

Rheumatoid arthritis is linked to Proteus--the evidence.

Rheumatoid arthritis (RA) is a chronic inflammatory arthritic and potentially disabling condition, mainly affecting women of middle age and having characteristic clinical features. Various microbial agents were implicated in the causation of RA. Extensive literature based on the results of various genetic, microbiological, molecular, and immunological studies carried out by independent research groups supports the role of Proteus mirabilis bacteria in the etiopathogenesis of RA. New diagnostic markers and criteria and the use of a novel therapeutic protocol in the form of antibiotic and dietary measures are suggested to be used together with current treatments in the management of RA. Prospective longitudinal studies with the use of antimicrobial measures in patients with RA are required to establish the therapeutic benefit of this microbe-disease association.

Antibodies, Bacterial↗
PubMed2005

Preventive and therapeutic administration of an indigenous Lactobacillus sp. strain against Proteus mirabilis ascending urinary tract infection in a mouse model.

Probiotics are increasingly being considered as non-pharmaceutical and safe potential alternatives for the treatment and prevention of a variety of pathologies including urinary tract infections. These are the most common infections in medical practice and are frequently treated with antibiotics, which have generated an intense selective pressure over bacterial populations. Proteus mirabilis is a common cause of urinary tract infections in catheterised patients and people with abnormalities of the urinary tract. In this work we isolated, identified and characterised an indigenous Lactobacillus murinus strain (LbO2) from the vaginal tract of a female mouse. In vitro characterisation of LbO2 included acid and bile salts tolerance, growth in urine, adherence to uroepithelial cells and in vitro antimicrobial activity. The selected strain showed interesting properties, suitable for its use as a probiotic. The ability of LbO2 to prevent and even treat ascending P. mirabilis urinary tract infection was assessed using an experimental model in the mouse. Kidney and bladder P. mirabilis counts were significantly lower in mice preventively treated with the probiotic than in non-treated mice. When LbO2 was used for therapeutic treatment, bladder counts of treated mice were significantly lower although no significant differences were detected in P. mirabilis kidney colonisation of treated and non-treated animals. These results are encouraging and prompt further research related to probiotic strains and the basis of their effects for their use in human and animal health.

Animals↗
PubMed1987

A hospital outbreak caused by a chlorhexidine and antibiotic-resistant Proteus mirabilis.

An outbreak of urinary-tract infection involving a strain of Proteus mirabilis resistant to gentamicin and several other antibiotics affected 90 patients in Southampton between July 1980 and May 1985. The outbreak strain was also resistant to chlorhexidine and this, in combination with the antibiogram and Dienes' test, permitted differentiation from other P. mirabilis strains. The outbreak had features in common with other Enterobacteriaceae outbreaks, although certain aspects of the population involved have made it particularly difficult to control. The outbreak commenced shortly after the introduction of a catheter care policy which involved the use of chlorhexidine, and although the majority of the cases were colonized before this policy was enforced, chlorhexidine had been used extensively for other procedures within the district. Preliminary evidence suggests that there is no genetic linkage between the chlorhexidine and multiple antibiotic resistance.

Age Factors↗
PubMed1994

Genetic organization and complete sequence of the Proteus mirabilis pmf fimbrial operon.

Proteus mirabilis, commonly associated with urinary tract infection, pyelonephritis and bacteremia, produces a number of fimbriae, including PMF (P. mirabilis fimbriae). Genes encoding PMF were isolated and the complete nucleotide (nt) sequence was determined. The pmf gene cluster, encoded by 5655 bp, predicts five polypeptides: PmfA (18,921 Da), PmfC (93,107 Da), PmfD (28,208 Da), PmfE (38,875 Da) and PmfF (19,661 Da). PmfA, PmfC, PmfD and PmfF share > 25% amino acid (aa) sequence identity with gene products of the pap, mrp and sfa fimbrial gene clusters. PmfE shares no similarity with any polypeptide in the SwissProt database. No regulatory gene(s) or regulatory elements were evident in the sequence. The pmf cluster shares common features with other enteric fimbrial gene clusters, but also displays features that are unique.

Amino Acid Sequence↗
PubMed2006

Dissemination of Proteus mirabilis isolates harboring CTX-M-14 and CTX-M-3 beta-lactamases at 2 hospitals in Taiwan.

From February to June 2003, 111 clinical isolates of Proteus mirabilis were mainly isolated from patients with respiratory or urinary tract infections hospitalized at 3 district hospitals (A, B, C) in central Taiwan. Among them, 34 (30.6%) strains, isolated within 2 hospitals (A and B), exhibited nonsusceptibility to cefotaxime with significant reduction of MIC (> or = 3 log2 dilution) by the effect of clavulanic acid, which confirmed the phenotype of extended-spectrum beta-lactamases (ESBLs). These ESBL producers were coresistant to gentamicin, isepamicin, and amikacin, but remained susceptible to ceftazidime (MIC, < or = 0.5 microg/mL) and meropenem (MIC, <0.5 microg/mL). By isoelectric focusing analysis, polymerase chain reaction, and nucleotide sequencing, we detected the presence of CTX-M-14 in 33 strains and CTX-M-3 in 6 strains (5 strains harboring both CTX-M-14 and CTX-M-3 enzymes). These beta-lactamase genes can be successfully transferred by the conjugative plasmid. Molecular epidemiology of the 34 ESBL-producing P. mirabilis strains by pulsed-field gel electrophoresis using SfiI restriction enzyme revealed 9 different genotypes, suggesting epidemic clones with intra- and interhospital spread. In conclusion, the broadly extended clonal spreading of CTX-M-type P. mirabilis was first discovered at the district hospitals in Taiwan.

Bacterial Proteins↗
PubMed2006

The first detection of CTX-M-14 extended-spectrum beta-lactamase among diverse beta-lactamase-producing Proteus mirabilis clinical isolates.

CTX-M-14- and -2-like extended-spectrum beta-lactamases were detected in 5 and 1 Proteus mirabilis isolates, respectively, among 92 non-duplicate strains tested from December 2002 to September 2003. This is the first report of the CTX-M-14 enzyme in P. mirabilis to the best of our knowledge and suggests that the CTX-M-type enzyme is gradually spreading to this species. bla(TEM), bla(SHV-1), and/or bla(OXA-10) alleles were also detected in 35 ampicillin-resistant isolates tested.

Adult↗
PubMed2004

Mucosal vaccination of mice with recombinant Proteus mirabilis structural fimbrial proteins.

Proteus mirabilis, a common cause of urinary tract infection (UTI), expresses several types of fimbria including mannose-resistant/Proteus-like fimbriae (MRP), uroepithelial cell adhesin (UCA), renamed non-agglutinating fimbriae (NAF) by some authors, and P. mirabilis fimbriae (PMF), which are potentially involved in adhesion to the uroepithelium. In this study, we immunised different groups of mice with recombinant structural subunits of these fimbriae (MrpA, UcaA and PmfA) using two mucosal routes (nasal and transurethral) and we transurethrally challenged the animals with a P. mirabilis uropathogenic isolate. Induction of specific serum and urine IgG and IgA was measured to assess the potential role of the humoral immune response in protection against experimental ascending P. mirabilis UTI. Intranasally MrpA- and UcaA-immunised mice were protected against P. mirabilis ascending UTI, since recovery of bacteria from kidneys and bladders was significantly lower than in PBS-treated mice, and both fimbrial subunits significantly induced specific serum and urine antibodies. Only MrpA and PmfA transurethrally immunised animals were protected only at the kidney level, and in this case only MrpA-immunised mice exhibited significant serum IgG induction. Correlation analysis did not show a significant relationship between serum and urine specific antibody response and protection observed against infection. Our results suggest that an immunisation strategy based on structural fimbrial proteins may be useful to prevent P. mirabilis UTI. Further studies are being carried out to characterise the immune and inflammatory response induced by P. mirabilis recombinant fimbrial subunits.

Administration, Intranasal↗
PubMed2000

The structure of the carbohydrate backbone of the core-lipid A region of the lipopolysaccharide from Proteus mirabilis serotype O28.

The following structure of the lipid A-core region of the lipopolysaccharide (LPS) from Proteus mirabilis serotype O28 was determined using NMR, MS, and chemical analysis of the core oligosaccharide, obtained by mild acid hydrolysis of LPS, and of the products of alkaline deacylation of the LPS: carbohydrate sequence [see text] where S = beta-GalALys (amide of beta-D-galactopyranosyluronic acid with the alpha-amino group of L-lysine) or beta-GalALys4PEtN are present in the ratio of approximately 1:1. beta-GalA and Ara4N (indicated by bold italics) are present in non stoichometric amount. All sugars are present in the pyranose form and all except L-Ara4N have the D configuration.

Antigens, Bacterial↗