Identification of MrpI as the sole recombinase that regulates the phase variation of MR/P fimbria, a bladder colonization factor of uropathogenic Proteus mirabilis.
Proteus mirabilis is a common cause of urinary tract infection (UTI) in individuals with structural abnormalities or long-term catheterization. The expression of mannose-resistant/Proteus-like (MR/P) fimbria is phase variable because of the inversion of a 251 bp DNA fragment that carries the promoter for the mrp operon. Previous studies have shown that mrpI, which is transcribed divergently from the mrp operon, encodes a recombinase capable of switching the orientation of this invertible element. In this study, we constructed isogenic mrpI null mutants from a clinical isolate of P. mirabilis, HI4320. A polymerase chain reaction (PCR)-based invertible element assay revealed that the isogenic mrpI null mutants were locked in one phase, either expressing (locked on) MR/P fimbriae or not (locked off), which indicated that MrpI was the sole recombinase that regulated the phase variation of MR/P fimbria. The locked-on and locked-off mutants were evaluated for virulence in the CBA mouse model of ascending UTI by co-challenges with each other and with the wild-type strain. Results from these experiments demonstrated conclusively that the MR/P fimbria was a critical bladder colonization factor of uropathogenic P. mirabilis and also suggested that the ability to switch off the expression of MR/P fimbria might be important for kidney colonization.
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Xin
X
Li
C Virginia
CV
Lockatell
David E
DE
Johnson
Harry L T
HL
Mobley
D000818:Animals; D001426:Bacterial Proteins; D004254:DNA Nucleotidyltransferases / Q000502:physiology*; D010861:Fimbriae, Bacterial / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D005816:Genetic Complementation Test; D007668:Kidney / Q000382:microbiology; D008358:Mannose / Q000378:metabolism*; D051379:Mice; D008808:Mice, Inbred CBA; D023421:Models, Animal; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011512:Proteus Infections / Q000378:metabolism* / Q000382:microbiology; D011513:Proteus mirabilis / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D045522:Recombinases; D001743:Urinary Bladder / Q000382:microbiology
D001426:Bacterial Proteins; D045522:Recombinases; C079120:mrpA protein, Proteus mirabilis; D004254:DNA Nucleotidyltransferases; D008358:Mannose