The role of cycle inhibiting factor in burkholderia pseudomallei

Abstract

Burkholderia pseudomallei, a causative agent of melioidosis, harbor several virulence factors crucial for its pathogenesis. A cycle-inhibiting factor (Cif) is one of bacterial effector molecules produced by B. pseudomallei, however the role of this protein is still unclear. In our previous study, we constructed a B. pseudomallei cif mutant to explore the function of Cif in B. pseudomallei infection. Infection of U937 macrophage with B. pseudomallei revealed that host cell contact was required for the secretion of Cif. Interestingly, Cif was secreted in the host cell in a manner dependent on the Bsa type III secretion system. Moreover, the responsibility of Cif is likely important for B. pseudomallei pathogenesis as we found B. pseudomallei cif mutant showed significant defects in abilities to induce plaque formation and cytotoxicity of HeLa cells when compared to the wild type. We further investigated the host protein expression profiles of infected HeLa cells using mass spectrometry. Investigation by this technique identified 97 up-regulated and 166 down-regulated proteins that significantly altered in HeLa cells infected with chbP mutant compared with that of B. pseudomallei wild type strain. Among these, some are associated with metabolic process, catalytic activity and signaling pathways. Thus, based upon our findings, we indicate a requirement of Cif that deliver via Bsa apparatus in B. pseudomallei infection, and the role of Cif might be involved with regulation of the host cell expression to alter the host cell functions which benefit for the pathogenesis of B. pseudomallei.