title: Zinc uptake contributes to motility and provides a competitive advantage to Proteus mirabilis during experimental urinary tract infection.
abstract: Proteus mirabilis, a Gram-negative bacterium, represents a common cause of complicated urinary tract infections in catheterized patients or those with functional or anatomical abnormalities of the urinary tract. ZnuB, the membrane component of the high-affinity zinc (Zn(2+)) transport system ZnuACB, was previously shown to be recognized by sera from infected mice. Since this system has been shown to contribute to virulence in other pathogens, its role in Proteus mirabilis was investigated by constructing a strain with an insertionally interrupted copy of znuC. The znuC::Kan mutant was more sensitive to zinc limitation than the wild type, was outcompeted by the wild type in minimal medium, displayed reduced swimming and swarming motility, and produced less flaA transcript and flagellin protein. The production of flagellin and swarming motility were restored by complementation with znuCB in trans. Swarming motility was also restored by the addition of Zn(2+) to the agar prior to inoculation; the addition of Fe(2+) to the agar also partially restored the swarming motility of the znuC::Kan strain, but the addition of Co(2+), Cu(2+), or Ni(2+) did not. ZnuC contributes to but is not required for virulence in the urinary tract; the znuC::Kan strain was outcompeted by the wild type during a cochallenge experiment but was able to colonize mice to levels similar to the wild-type level during independent challenge. Since we demonstrated a role for ZnuC in zinc transport, we hypothesize that there is limited zinc present in the urinary tract and P. mirabilis must scavenge this ion to colonize and persist in the host.
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: Greta R
authors.initials: GR
authors.lastname: Nielubowicz
authors.forename: Sara N
authors.initials: SN
authors.lastname: Smith
authors.forename: Harry L T
authors.initials: HL
authors.lastname: Mobley
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002413:Cations, Divalent / Q000378:metabolism; D005408:Flagellin / Q000096:biosynthesis; D017353:Gene Deletion; D005816:Genetic Complementation Test; D006801:Humans; D007501:Iron / Q000378:metabolism; D008124:Locomotion; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D008670:Metals / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D016254:Mutagenesis, Insertional; D009735:Nursing Homes; D011512:Proteus Infections / Q000382:microbiology*; D011513:Proteus mirabilis / Q000302:isolation & purification / Q000378:metabolism* / Q000472:pathogenicity*; D014552:Urinary Tract Infections / Q000382:microbiology*; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism; D015032:Zinc / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D002413:Cations, Divalent; D026901:Membrane Transport Proteins; D008670:Metals; D037521:Virulence Factors; D005408:Flagellin; D007501:Iron; D015032:Zinc
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