title: The high-affinity phosphate transporter Pst is a virulence factor for Proteus mirabilis during complicated urinary tract infection.
abstract: Proteus mirabilis is a ubiquitous bacterium associated with complicated urinary tract infection (UTI). Mutagenesis studies of the wild-type strain HI4320 in the CBA mouse model of ascending UTIs have identified attenuated mutants with transposon insertions in genes encoding the high-affinity phosphate transporter Pst (pstS, pstA). The transcription of the pst operon (pstSCAB-phoU) and other members of the phosphate regulon of Escherichia coli, including alkaline phosphatase (AP), are regulated by the two-component regulatory system PhoBR and are repressed until times of phosphate starvation. This normal suppression was relieved in pstS::Tn5 and pstA::Tn5 mutants, which constitutively produced AP regardless of growth conditions. No significant growth defects were observed in vitro for the pst mutants during the independent culture or coculture studies in rich broth, phosphate-limiting minimal salts medium, or human urine. Mutants complemented with the complete pst operon repressed AP synthesis in vitro and colonized the mouse bladder in numbers comparable to the wild-type strain HI4320. Therefore, the Pst transport system imparts a significant in vivo advantage to wild-type P. mirabilis that is not required for in vitro growth. Thus, the Pst transporter has satisfied molecular Koch's postulates as a virulence factor in the pathogenesis of urinary tract infection caused by P. mirabilis.
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, University of Maryland Baltimore, Baltimore, MD, USA.
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Jacobsen
authors.forename: Mary C
authors.initials: MC
authors.lastname: Lane
authors.forename: Jean M
authors.initials: JM
authors.lastname: Harro
authors.forename: Mark E
authors.initials: ME
authors.lastname: Shirtliff
authors.forename: Harry L T
authors.initials: HL
authors.lastname: Mobley
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology*; D004251:DNA Transposable Elements; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D029968:Escherichia coli Proteins / Q000096:biosynthesis; D005260:Female; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D005816:Genetic Complementation Test; D051379:Mice; D008808:Mice, Inbred CBA; D016254:Mutagenesis, Insertional; D011512:Proteus Infections / Q000382:microbiology*; D011513:Proteus mirabilis / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D001743:Urinary Bladder / Q000382:microbiology; D014552:Urinary Tract Infections / Q000382:microbiology*; D014556:Urine / Q000382:microbiology; D037521:Virulence Factors / Q000502:physiology*
chemical_list: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D004251:DNA Transposable Elements; D029968:Escherichia coli Proteins; D037521:Virulence Factors; C078408:phosphate-specific transport protein A, bacteria; D000469:Alkaline Phosphatase