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dc.contributor.authorWong, Yee-Chin
dc.contributor.authorAbd El Ghany, Moataz
dc.contributor.authorNaeem, Raeece
dc.contributor.authorYap, Soon-Joo
dc.contributor.authorHoh, Chee-Choong
dc.contributor.authorPain, Arnab
dc.contributor.authorNathan, Sheila
dc.date.accessioned2018-05-30T07:22:57Z
dc.date.available2018-05-30T07:22:57Z
dc.date.issued2018-05-29
dc.identifier.citationWong Y-C, Abd El Ghany M, Ghazzali RNM, Yap S-J, Hoh C-C, et al. (2018) Genetic Determinants Associated With in Vivo Survival of Burkholderia cenocepacia in the Caenorhabditis elegans Model. Frontiers in Microbiology 9. Available: http://dx.doi.org/10.3389/fmicb.2018.01118.
dc.identifier.issn1664-302X
dc.identifier.doi10.3389/fmicb.2018.01118
dc.identifier.urihttp://hdl.handle.net/10754/627990
dc.description.abstractA Burkholderia cenocepacia infection usually leads to reduced survival and fatal cepacia syndrome in cystic fibrosis patients. The identification of B. cenocepacia essential genes for in vivo survival is key to designing new anti-infectives therapies. We used the Transposon-Directed Insertion Sequencing (TraDIS) approach to identify genes required for B. cenocepacia survival in the model infection host, Caenorhabditis elegans. A B. cenocepacia J2315 transposon pool of ∼500,000 mutants was used to infect C. elegans. We identified 178 genes as crucial for B. cenocepacia 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 O-antigen biosynthesis. Deletion of the glycosyltransferase gene wbxB and a histone-like nucleoid structuring (H-NS) protein-encoding gene (BCAL0154) reduced bacterial accumulation and attenuated virulence in C. elegans. Further analysis using quantitative RT-PCR indicated that BCAL0154 modulates B. cenocepacia pathogenesis via transcriptional regulation of motility-associated genes including fliC, fliG, flhD, and cheB1. This screen has successfully identified genes required for B. cenocepacia survival within the host-associated environment, many of which are potential targets for developing new antimicrobials.
dc.description.sponsorshipThis study was supported by the grants 06-05-16-MB003 from the Ministry of Science, Technology and Innovation Malaysia and DIP-2015-022 from Universiti Kebangsaan Malaysia awarded to SN. Y-CW was supported by a MyBrain15 Scholarship from the Ministry of Higher Education Malaysia. Part of this work was conducted in KAUST, funded by the faculty baseline fund BAS/1/1020-01-01 from KAUST to AP. We thank Prof. Herbert P. Schweizer (University of Florida, United States) for kindly providing the plasmid pEXKm5 and Dr. Chantratita Narisara (Mahidol University, Thailand) for her expert advice on mutant construction. We also thank Dr. Rui-Rui Wong for her technical assistance and and Ms. Jia-Shiun Khoo (Codon Genomics) for bioinformatics support.
dc.publisherFrontiers Media SA
dc.relation.urlhttps://www.frontiersin.org/articles/10.3389/fmicb.2018.01118/full
dc.rightsArchived with thanks to Frontiers in Microbiology
dc.titleGenetic Determinants Associated With in Vivo Survival of Burkholderia cenocepacia in the Caenorhabditis elegans Model
dc.typeArticle
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.contributor.departmentBioscience Program
dc.contributor.departmentComputational Bioscience Research Center (CBRC)
dc.identifier.journalFrontiers in Microbiology
dc.eprint.versionPublisher's Version/PDF
dc.contributor.institutionSchool of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi, Malaysia
dc.contributor.institutionThe Westmead Institute for Medical Research and The Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney, NSW, Australia
dc.contributor.institutionCodon Genomics, Seri Kembangan, Malaysia
kaust.personAbd El Ghany, Moataz
kaust.personNaeem, Raeece
kaust.personPain, Arnab
kaust.grant.numberBAS/1/1020-01-01
refterms.dateFOA2018-06-14T05:13:40Z


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