Contribution of Outer Membrane Porin (Omp) K36 to Klebsiella pneumoniae induced Liver Abscess

Abstract

Introduction: Pyogenic liver abscess is usually caused by multiple bacterial infections. This disease can be caused by single microorganism, Klebsiella pneumoniae that has been reported in Asia, North America and Europe. Many virulence factors of K. pneumoniae have identified including capsular polysaccharide, lipopolysaccharide, serum resistance, adhesins and siderophores. Previously, we demonstrated the virulent effect of outer membrane porin (OMP) K 36 by a lethality study. However, the role of OmpK36 in liver abscess pathogenesis is still unclear.Objective: In this study, a virulent K. pneumoniae strain NVT-1002 and OmpK36 deficient mutant (ΔOMPK) were used to examine the contribution of OmpK36 to liver abscess. Liver injuries and inflammatory cytokines expression were detected by tissue section and enzyme linked-immunosorbent assay respectively. The toxic effect of OmpK36 to human hepatoma cell (HepG2) was tested by bacterial infections and the treatment with OmpK36 recombinant protein. Results:The Results demonstrated that the NVT-1002 induced sever liver injuries while little or no damage was found in mice injected with OmpK36. Expression of serum and liver cytokines including TNF-α, IL-1β, IL-6 and IL-10 were elevated after injection of NVT-1002, meanwhile, only IL-1β was transiently elevated in OmpK36 group. Interestingly, OmpK36 recombinant protein showed no toxic effect to HepG2 cells, and the virulence of OmpK36 mutant to HepG2 was not altered compared to NVT-1002 group. Conclusion:In conclusion, OmpK36 contributes to the K. pneumoniae induced liver abscess and inflammatory responses. The virulent effect of OmpK36 is not mediated by the protein itself, but other uncertain mechanisms. OmpK36 may be a therapeutic target in K. pneumoniae infection. Contribution of Outer Keywords:OmpK36, Virulence, Liver abscess, Inflammatory Original ArticleOpen Access IntroductionKlebsiella pneumoniae have been documented as the common factor for cryptogenic liver abscess in Asia Pacific [1,2]. Similar findings in North America and Europe have also been reported [3][4][5]. Several virulent factors of K. pneumoniae were discovered and these factors are almost related to specific capsular polysaccharides (CPS) [2,[6][7][8]. Accumulating reports have indicated that the capsule is essential to the virulence of Klebsiella species [9][10][11]. Up to now, the capsular antigen have been classified into 77 serotypes , and serotype K1 and K2 capsular antigen were found to comprise virulence in mouse peritonitis model, whereas isolates of serotypes other than K1 or K2 were with little or no virulence [5,12].Outer membrane porins (OMP) are proteins that cross a cellular membrane and contribute to the diffusion of molecules. Many studies have showed OMPs play important roles in antimicrobial resistance [13,14]. Previously, we have demonstrated the virulent effects of OMPK 36 by an animal study [15]. In this report, the results of animal lethality study showed that the virulence of OmpK36 mutant was reduced about 100 fold c...