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

Journal of Medical Microbiology
Stephanie D HimpslHarry L T Mobley

Abstract

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...Continue Reading

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Citations

Oct 9, 2012·Nature Reviews. Microbiology·Chelsie E Armbruster, Harry L T Mobley
Jul 14, 2010·Journal of Bacteriology·Eleonora AquiliniMiguel Regué
Sep 17, 2013·PLoS Pathogens·Christopher J AlteriHarry L T Mobley
Apr 24, 2014·International Journal of Molecular Sciences·Eleonora AquiliniJuan M Tomás
Oct 7, 2010·Molecular Microbiology·Stephanie D HimpslHarry L T Mobley
Feb 28, 2019·Letters in Applied Microbiology·H PellingB V Jones
Feb 10, 2018·EcoSal Plus·Chelsie E ArmbrusterMelanie M Pearson
Nov 7, 2015·Microbiology Spectrum·Jessica N Schaffer, Melanie M Pearson

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