oxyR, a LysR-type regulator involved in Klebsiella pneumoniae mucosal and abiotic colonization.
Colonization of the gastrointestinal tract is the first event in Klebsiella pneumoniae nosocomial infections, followed by colonization of the bladder or respiratory tract or entry into the bloodstream. To survive in the host, bacteria must harbor specific traits and overcome multiple stresses. OxyR is a conserved bacterial transcription factor with a key role both in the upregulation of defense mechanisms against oxidative stress and in pathogenesis by enhancing biofilm formation, fimbrial expression, and mucosal colonization. A homolog of oxyR was detected in silico in the K. pneumoniae sequenced genome and amplified from the LM21 wild-type strain. To determine the role of oxyR in K. pneumoniae host-interaction processes, an oxyR isogenic mutant was constructed, and its behavior was assessed. At concentrations lower than 10(7) ml(-1), oxyR-deficient organisms were easily killed by micromolar concentrations of H(2)O(2) and exhibited typical aerobic phenotypes. The oxyR mutant was impaired in biofilm formation and types 1 and 3 fimbrial gene expression. In addition, the oxyR mutant was unable to colonize the murine gastrointestinal tract, and in vitro assays showed that it was defective in adhesion to Int-407 and HT-29 intestinal epithelial cells. The behavior of the oxyR mutant was also determined under hostile conditions, reproducing stresses encountered in the gastrointestinal environment: deletion of oxyR resulted in higher sensitivity to bile and acid stresses but not to osmotic stress. These results show the pleiotropic role of oxyR in K. pneumoniae gastrointestinal colonization.
Hennequin
Claire
C
Université de Clermont 1, UFR Pharmacie, Laboratoire de Bactériologie, 28 Place Henri Dunant, Clermont-Ferrand F-63001, France. claire.hennequin@u-clermont1.fr
Forestier
Christiane
C
D000143:Acids / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D001646:Bile / Q000378:metabolism; D018441:Biofilms / Q000254:growth & development; D010861:Fimbriae, Bacterial / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000382:microbiology; D017353:Gene Deletion; D007710:Klebsiella Infections / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000472:pathogenicity*; D051379:Mice; D050296:Microbial Viability; D008969:Molecular Sequence Data; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics / Q000502:physiology*
D000143:Acids; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C545271:OxyR protein, Klebsiella pneumoniae; D012097:Repressor Proteins; D014157:Transcription Factors; D037521:Virulence Factors; C073470:LysR protein, Bacteria