Within-host evolution of Burkholderia pseudomallei in four cases of acute melioidosis

Autor: Jeffrey T. Foster, Sharon J. Peacock, Talima Pearson, Apichai Tuanyok, David M. Wagner, Amy J. Vogler, Heidie Hornstra, Rebecca E. Colman, Erin P. Price, Derek S. Sarovich, Paul Keim, Benjamin Leadem, Jennifer L. Ginther, Tamara L. Max, Direk Limmathurotsakul, Julia Dale
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Male
Burkholderia pseudomallei
Melioidosis
Minisatellite Repeats
Infectious Diseases/Bacterial Infections
Serial passage
Genotype
Biology (General)
Pathogen
Phylogeny
Genetics
0303 health sciences
Microbiology/Microbial Evolution and Genomics
Middle Aged
Genetics and Genomics/Microbial Evolution and Genomics
Electrophoresis
Gel
Pulsed-Field
3. Good health
Evolutionary Biology/Microbial Evolution and Genomics
Female
Research Article
Adult
QH301-705.5
Molecular Sequence Data
Immunology
Multiple Loci VNTR Analysis
Biology
Microbiology
Evolution
Molecular
03 medical and health sciences
Tandem repeat
Virology
medicine
Humans
Molecular Biology
Genotyping
030304 developmental biology
Base Sequence
030306 microbiology
RC581-607
medicine.disease
biology.organism_classification
Genes
Bacterial
Mutation
Parasitology
Immunologic diseases. Allergy
Zdroj: PLoS Pathogens, Vol 6, Iss 1, p e1000725 (2010)
PLoS Pathogens
Popis: 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.
Author Summary While both viral and bacterial pathogens have been shown to undergo genetic changes over the course of a chronic infection, this phenomenon has not been studied during an acute infection and as such is not well understood. Here, we examined within-host evolution of the pathogen Burkholderia pseudomallei during acute infection. B. pseudomallei causes the disease melioidosis, a significant cause of morbidity and mortality in many tropical regions of the world. We obtained multiple B. pseudomallei colonies from several tissue sites of four patients presenting with acute melioidosis in order to characterize how this bacterium evolves within the human host over a short period of time. By monitoring changes in rapidly evolving genetic regions, we found high levels of diversity of B. pseudomallei populations within a single patient, and even within a single body site. Comparison of these within-host mutation rates with in vitro mutation data enabled us to identify the most likely spatial migration of within-host populations and correlate these findings with clinical data to determine, in most cases, the origin of infection. Our study provides new insights into the evolution of bacterial pathogens during an acute infection, and lays the foundation for similar studies in other infectious agents.
Databáze: OpenAIRE
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