The Role of Cycle Inhibiting Factor in Burkholderia pseudomallei Neuroinfections: Structural and Functional Insights

Functional studies demonstrated enhanced neuronal plaque formation in variants VT1, VT2, VT5, and VT15. Interestingly, no significant differences were observed between bpss1385 WT and VT3, VT4, VT6, or VT9, despite structural divergences in VT4. This suggests a complex relationship between Cif structure and B. pseudomallei pathogenesis.

We further gained insights into the role of Cif in neuronal cells by proteomic analysis, identified 52 SH-SY5Y proteins with significant expression changes when comparing cif knockout mutant infection to parental strain (K96243) infection. These proteins, mainly involved in mRNA metabolism and cellular structure, indicate the involvement of Cif in disrupting host processes for bacterial survival. These findings emphasize the importance of Cif in B. pseudomallei pathogenesis, particularly in manipulating host neuronal pathways, potentially contributing to enhanced virulence in certain variants within neuronal environments.