Within-Host Evolution of Burkholderia pseudomallei in Four Cases of Acute Melioidosis

PLoS Pathogens

Paul Keim¹  Tamara L. Max²  Talima Pearson²  Rebecca E. Colman³  Direk Limmathurotsakul³  Derek S. Sarovich³  Sharon J. Peacock³  Jennifer L. Ginther³  Apichai Tuanyok³  Amy J. Vogler³  Benjamin Leadem³  Jeffrey T. Foster³  David M. Wagner³  Julia L. Dale³  Erin P. Price³  Heidie M. Hornstra⁴ 

[1] Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;Northern Arizona University, Center for Microbial Genetics and Genomics, Flagstaff, Arizona, United States of America;Translational Genomics Research Institute, Phoenix, Arizona, United States of America

关键词: Phylogenetics;    Melioidosis;    Abscesses;    Urine;    Bacterial evolution;    Human genetics;    Blood;    Insertion mutation;   

DOI  :  10.1371/journal.ppat.1000725

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Little is currently known about bacterial pathogen evolution and adaptation within the host during acute infection. Previous studies of Burkholderia pseudomallei, the etiologic agent of melioidosis, have shown that this opportunistic pathogen mutates rapidly both in vitro and in vivo at tandemly repeated loci, making this organism a relevant model for studying short-term evolution. In the current study, B. pseudomallei isolates cultured from multiple body sites from four Thai patients with disseminated melioidosis were subjected to fine-scale genotyping using multilocus variable-number tandem repeat analysis (MLVA). In order to understand and model the in vivo variable-number tandem repeat (VNTR) mutational process, we characterized the patterns and rates of mutations in vitro through parallel serial passage experiments of B. pseudomallei. Despite the short period of infection, substantial divergence from the putative founder genotype was observed in all four melioidosis cases. This study presents a paradigm for examining bacterial evolution over the short timescale of an acute infection. Further studies are required to determine whether the mutational process leads to phenotypic alterations that impact upon bacterial fitness in vivo. Our findings have important implications for future sampling strategies, since colonies in a single clinical sample may be genetically heterogeneous, and organisms in a culture taken late in the infective process may have undergone considerable genetic change compared with the founder inoculum.

【 授权许可】

CC BY