The role of pgaC in Klebsiella pneumoniae virulence and biofilm formation

Background: Klebsiella pneumoniae has emerged as one of the major pathogens for community-acquired and nosocomial infections. A four-gene locus that had a high degree similarity with Escherichia coli pgaABCD and Yersinia pestis hmsHFRS was identified in K.pneumoniae genomes. The pgaABCD in E.coli encodes the envelope-spanning Pga machinery for the synthesis and secretion of poly-β-linked N-acetylglucosamine (PNAG). In a limited number of phylogenetically diverse bacteria, PNAG was demonstrated to mediate biofilm formation and had a role in the host-bacteria interactions. The presence of conserved pgaABCD locus among various K.pneumoniae strains suggested a putative requirement of PNAG for this bacterium. Results: In this study, an in-frame deletion of pgaC was generated in K.pneumoniae CG43 and named δ. pgaC. The loss of pgaC affected the production of PNAG and attenuated the enhancement of invitro biofilm formation upon the addition of bile salts mixture. In mouse models, δ. pgaC exhibited a weakened ability to colonize the intestine, to disseminate extraintestinally, and to induce a systemic infection when compared to K.pneumoniae CG43. Conclusions: Our study demonstrated that pgaC participated in the bile salts induced biofilm formation and was required for K.pneumoniae virulence invivo.