AUTHOR=Wong Yee-Chin , Abd El Ghany Moataz , Ghazzali Raeece N. M. , Yap Soon-Joo , Hoh Chee-Choong , Pain Arnab , Nathan Sheila 

TITLE=Genetic Determinants Associated With in Vivo Survival of Burkholderia cenocepacia in the Caenorhabditis elegans Model

JOURNAL=Frontiers in Microbiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2018.01118

DOI=10.3389/fmicb.2018.01118

ISSN=1664-302X

ABSTRACT=<p>A <italic>Burkholderia cenocepacia</italic> infection usually leads to reduced survival and fatal <italic>cepacia</italic> syndrome in cystic fibrosis patients. The identification of <italic>B. cenocepacia</italic> essential genes for <italic>in vivo</italic> survival is key to designing new anti-infectives therapies. We used the Transposon-Directed Insertion Sequencing (TraDIS) approach to identify genes required for <italic>B. cenocepacia</italic> survival in the model infection host, <italic>Caenorhabditis elegans</italic>. A <italic>B. cenocepacia</italic> J2315 transposon pool of ∼500,000 mutants was used to infect <italic>C. elegans</italic>. We identified 178 genes as crucial for <italic>B. cenocepacia</italic> survival in the infected nematode. The majority of these genes code for proteins of unknown function, many of which are encoded by the genomic island BcenGI13, while other gene products are involved in nutrient acquisition, general stress responses and LPS <italic>O</italic>-antigen biosynthesis. Deletion of the glycosyltransferase gene <italic>wbxB</italic> and a histone-like nucleoid structuring (H-NS) protein-encoding gene (BCAL0154) reduced bacterial accumulation and attenuated virulence in <italic>C. elegans</italic>. Further analysis using quantitative RT-PCR indicated that BCAL0154 modulates <italic>B. cenocepacia</italic> pathogenesis via transcriptional regulation of motility-associated genes including <italic>fliC, fliG, flhD</italic>, and <italic>cheB1</italic>. This screen has successfully identified genes required for <italic>B. cenocepacia</italic> survival within the host-associated environment, many of which are potential targets for developing new antimicrobials.</p>