A Genomic Survey of Positive Selection in Burkholderia pseudomallei Provides Insights into the Evolution of Accidental Virulence

PLoS Pathogens

Richard W. Titball¹  Angela E. Essex-Lopresti¹  Timothy Atkins¹  Mitali Sarkar-Tyson¹  Catherine Ong²  Donald Woods³  Arvind Pratap Singh⁴  Christina Nilsson⁴  Wing-Kin Sung⁴  Yijun Ruan⁴  Tannistha Nandi⁴  Hui Hoon Chua⁴  Pramila Ariyaratne⁴  Jason F. Kreisberg⁴  Justin Boddey⁵  Paul Keim⁵  Ian Peak⁵  Patrick Tan⁶  Catherine Ronning⁶  Liliana Losada⁶  William C. Nierman⁷  Talima Pearson⁷  Ifor Beacham⁸ 

[1] Defence Science and Technology Laboratory, Porton Down, Salisbury, United Kingdom;Defense Medical and Environmental Research Institute, DSO National Laboratories, Singapore, Republic of Singapore;Faculty of Medicine, University of Calgary Health Sciences Centre, Calgary, Alberta, Canada;Genome Institute of Singapore, Singapore, Republic of Singapore;Institute for Glycomics, Griffith University (Gold Coast Campus), Southport, Queensland, Australia;J. Craig Venter Institute, Rockville, Maryland, United States of America;Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, Arizona, United States of America;School of Biosciences, University of Exeter, Exeter, United Kingdom

关键词: Comparative genomics;    Sequence alignment;    Multiple alignment calculation;    Gene prediction;    Host-pathogen interactions;    Sequence analysis;    Genome annotation;    Messenger RNA;   

DOI  :  10.1371/journal.ppat.1000845

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Certain environmental microorganisms can cause severe human infections, even in the absence of an obvious requirement for transition through an animal host for replication (“accidental virulence”). To understand this process, we compared eleven isolate genomes of Burkholderia pseudomallei (Bp), a tropical soil microbe and causative agent of the human and animal disease melioidosis. We found evidence for the existence of several new genes in the Bp reference genome, identifying 282 novel genes supported by at least two independent lines of supporting evidence (mRNA transcripts, database homologs, and presence of ribosomal binding sites) and 81 novel genes supported by all three lines. Within the Bp core genome, 211 genes exhibited significant levels of positive selection (4.5%), distributed across many cellular pathways including carbohydrate and secondary metabolism. Functional experiments revealed that certain positively selected genes might enhance mammalian virulence by interacting with host cellular pathways or utilizing host nutrients. Evolutionary modifications improving Bp environmental fitness may thus have indirectly facilitated the ability of Bp to colonize and survive in mammalian hosts. These findings improve our understanding of the pathogenesis of melioidosis, and establish Bp as a model system for studying the genetics of accidental virulence.

【 授权许可】

CC BY