Proteus mirabilis

A Microbial Biorealm page on the genus Proteus mirabilis

Classification

Higher order taxa

Domain; Phylum; Class; Order; family [Others may be used. Use NCBI link to find]

Species

NCBI: Taxonomy

Genus species

Genome structure

The genome sequence of P. mirabilis was completed in March 28, 2008 by Melanie M. Pearson identifying more than 3,658 coding sequences with 7 rRNA loci (Pearson et al., 2008). The genome’s total length is 4.063 Mb with a 28.8% GC content. P. mirabilis also carries a single plasmid with 36, 298 nucleotides. The plasmid itself does not contain any virulence genes but it may contain a bacteriocin and its immunity system. Within the genome is a genomic island involved in pathogenicity that codes for a type III secretion system comprising 24 genes used to inject bacterial proteins into a host genome. This type III system appears to be incorporated through horizontal gene transfer and is noted for its relatively smaller G+C content compared with the rest of the genome (Pearson et al., 2008). The genome sequence encodes 17 different types of fimbriae as well as a 54 kb flagellar regulon. The flagella made by the strain all come from a single locus. This information is characterized for a specific uropathogenic strain of P. mirabilis, HI4320. It is the first completed sequence of the bacterium out of more than 75 known strains that were identified using one dimensional SDS PAGE of cellular proteins mostly from human origin (Holmes et al., 2008).

Ecology

P. mirabilis can be found as a free-living microbe in soil and water. The organism is also normally found in the gastrointestinal tract of humans (Coker et al., 2000). Some believe that P. mirabilis has access to the bladder by infecting the periurethral area (Coker et al., 2000). P. mirabilis causes urinary tract infections primarily through indwelling catheters. Usually the urinary tract can wash out the microbe before it accumulates, but the catheter prevents this from happening. P. mirabilis can then adhere to the insides and outsides of the catheter, forming biofilm communities. Once established, these microbes pass through the urethra via swarming motility to the bladder. P. mirabilis binds to bladder epithelial cells where it eventually colonizes (Coker et al., 2000). P. mirabilis infection can also lead to the production of kidney and bladder stones. The bacteria colonize the stones as they form, making them less accessible to antibiotic attack (Pearson et al., 2008).

Application to Biotechnology

The antigens found on the outer membrane of P. mirabilis can potentially serve as targets for vaccines. So far, of the 37 identified immuno-reactive antigens, 23 are surface-bound proteins. Studies have shown that 2 iron acquisition proteins (PMI0842 and PMI2596) increase the virulence of P. mirabilis in the urinary tract (Nielubowicz et al., 2008). Since both of these proteins contribute to pathogenesis, they are good candidates for vaccines. Once an effective vaccine is made for these antigens, further research will determine whether or not these vaccines may be used against other bacteria that cause complicated urinary tract infections, such as Providencia and Morganella (Nielubowicz et al. 2008).

Current Research

P. mirabilis makes several different fimbriae that promote adhesion to mucosal surfaces. One of these fimbriae, called the mannose resistant Proteus-like fimbriae, has been highly present in patients associated with urinary tract infections (Xin et al., 1999). A mannose resistant Proteus-like gene (mrpH) present in the mrp operon of mrp fimbrae has been recently shown to be essential for functional adhesion of MR/P fimbrae(Xin etc. al, 1999). By using insertional mutagenesis, researchers noted that without the functional gene mrpH, there was less MR/P fimbriation. This information led to the conclusion that further research into the capabilities of the mrpH gene could lead to the production of a vaccine to render this gene ineffective. This would ultimately halt the ability of the Proteus mirabilis bacterium from attaching to mucosal surfaces, hindering infection (Xin et al., 1999).

P. mirabilis can be commonly present in healthy individuals as part of the normal mucosa. The bacterium becomes a significant problem mostly in individuals that have vulnerable immune systems and are in danger of nosocomial transmission, such as hospital patients (Farkosh et al., 2008). Current studies show that there are a number of antibiotics that were once effective against P. mirabilis that are now useless due to extended spectrum beta lactamases (ESBLs). These are enzymes passed through plasmids and are found in most of the Enterobacteriaceae. These plasmids were found within abscesses, blood, catheter tips, lung, peritoneal fluid, sputum, and throat culture (Farkosh et al., 2008). Detected in the 1980’s in Klebsiella and E. coli, these enzymes were found to hydrolyze antibiotic cephalosporin thus making it ineffective. The ESBL’s become highly dangerous when produced in copious amounts, conveying resistance to a large number of antibiotics used universally. The spread of these plasmids is primarily prevalent in healthcare facilities where patients have extended hospital stays, are using catheters, are within the ICU, have had recent surgery or are administered consistently with antibiotics.

References

Coker, Christopher, Carrie A. Poore, Xin Li, Harry L.T. Mobley. “Pathogenesis of Proteus mirabilis urinary tract infection.” Microbes and Infection. 2 (2000): 1497-1505.

Farkosh, S. Mary. “Extended-Spectrum beta-lactamase Producing Gram Negative Bacilli”. 2000. JHH HEIC. November 21, 2008. www.nosoweb.org/infectious_diseases/esbl.htm

Holmes, B., M. Costas, and AC Wood. "Typing of Proteus mirabilis from clinical sources by computerized analysis of electrophoretic protein patterns." Pub Med. Nov. 1991. NCBI. 21 Nov. 2008 <http://www.ncbi.nlm.nih.gov/pubmed/>.

Li, Xin; Johnson, E. David; and Mobley L.T Harry. “Requirement of MrpH for Mannose-Resistant Proteus-Like Fimbria-Mediated Hemagglutination by Proteus mirabilis”. American society of Microbiology. Infect Immun. 1999 June; 67(6): 2822–2833. [PubMed]

Nielubowicz, Greta R., Sara N. Smith, Harry L.T. Mobley. “Outer membrane antigens of the uropathogen Proteus mirabilis recognized by the humoral response during experimental murine urinary tract infection.” Infection and Immunity. 76.9 (2008): 4222-31.

Pearson MM, Sebaihia M, Churcher C, Quail MA, Seshasayee AS, Luscombe NM, Abdellah Z, Arrosmith C, Atkin B, Chillingworth T, Hauser H, Jagels K, Moule S, Mungall K, Norbertczak H, Rabbinowitsch E, Walker D, Whithead S, Thomson NR, Rather PN, Parkhill J, Mobley HL. “Complete genome sequence of uropathogenic Proteus mirabilis, a master of both adherence and motility.” J Bacteriol. 190.11 (2008): 4027-37.

Edited by Isioma Agboli, Michael Cao, Janice Love, and Fatima Morales