T6SS-5 and the cGAS-STING pathway in Burkholderia pseudomallei infection and immunity

Abstract

Burkholderia pseudomallei is a causative agent of melioidosis that can infect humans and animals in endemic countries, specifically in Southeast Asia and tropical Australia. A fundamental component for the pathogenesis of Burkholderia pseudomallei is the capability of the bacterium to enter, survive, replicate, and cause disease in a host cell by inducing the host cell fusion. Cell fusion results in multinucleated-giant cell formation, thus enabling the dissemination of Burkholderia pseudomallei intracellularly. cGAS reacts to Burkholderia pseudomallei infection by activating the cGAS-STING pathway and subsequently limiting host’s aberrant cell division and cellular replication by inducing autophagic cell death. In this review, we discuss the host-pathogen interactions between the type Ⅵ secretion system 5 (T6SS-5) of Burkholderia pseudomallei and human cGAS pathway in melioidosis infections. Since T6SS-5 is a main virulent factor in Burkholderia pseudomallei and the cGAS pathway is vital for host immune response, elucidating their functions is important for better understanding the pathogenesis of Burkholderia pseudomallei.

Keywords

Burkholderia pseudomallei / Melioidosis / T6SS-5 / cGAS-STING / IFN-1

Acknowledgments

We would like to thank Miss Ilia Elena for her time to proofread the manuscript.

Conflict of interest statement

The authors declare that there is no conflict of interest.

Funding

This study was supported by the Ministry of Higher Education Malaysia for Fundamental Research Grant Scheme with Project Code: FRGS/1/2019/SKK11/USM/02/5.

Authors’ contributions

NS and NZNMN were involved in conceptualization of the review. NS and NZNMN were responsible for writing the manuscript. YKMI contributed to preparing the figures. YKMI, NIM, AH, IA and ZZD reviewed and edited the manuscript. All authors read and approved the final draft of the manuscript.

Publisher’s note

The Publisher of the Journal remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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