Identification of Endogenous Mechanisms That Affect Klebsiella pneumoniaeGrowth in the Murine Host.

[摘要] Klebsiella pneumoniae is an opportunistic pathogen and a normal component of the host flora.The aim of this project was to investigate mechanisms that determine mucosal tissue colonization and infection by K. pneumoniae.In this study, a clinical respiratory isolate of Klebsiella pneumoniae, strain IA565, was found to be both non-pathogenic in a murine model of bacterial pneumonia and unable to colonize the lungs even during extreme immunosuppressive conditions.Strain IA565 was inoculated intranasally and intragastrically into immunocompetent and immunocompromised mice, germ-free mice, and mice with intestinal inflammation.When strain IA565 was both intranasally instilled and orally gavaged into wild type mice, this strain stably colonizes and persists in the nares and GI tract.Interestingly, intranasal inoculation of wild type (WT), germfree (GF), and severely immunocompromised mice with strain IA565 displayed similar CFU levels in the nasal cavity.Conversely, strain IA565 gastrointestinal (GI) tract CFU levels in GF mice are significantly higher than in WT mice suggesting that, in the presence of the normal gut microbiota, IA565 growth is controlled and maintained at low levels.In addition, mice with Citrobacter rodentium-induced gut inflammation displayed no change in IA565 GI colonization, compared to WT mice, and no change in the disease outcome. However, DSS-treated mice displayed significantly higher levels of IA565 gut CFU compared to WT levels demonstrating that host mediated inflammation can alter microbial colonization.Collectively, these data indicate that strain IA565 nasal cavity colonization can be achieved in immunocompetent, immunocompromised, and GF mice.Thus, nasal cavity colonization is independent of host factors and the indigenous microbiota.This is in contrast to IA565 GI colonization where host factors mediating certain types of inflammation can alter CFU levels and absence of the gut microbiota leads to increased IA565 growth.This study is the first to identify and describe mechanisms influencing the growth and behavior of a murine commensal organism.

[发布机构] University of Michigan

[效力级别] Commensalism

[关键词] Klebsiella Pneumoniae;Commensalism;Virulence Factors;Murine Colitis;Germ Free Mice;Microbiology and Immunology;Science;Microbiology & Immunology