Please use this identifier to cite or link to this item: https://hdl.handle.net/10137/11428
Title: Pathogen to commensal? Longitudinal within-host population dynamics, evolution, and adaptation during a chronic >16-year Burkholderia pseudomallei infection.
Authors: Pearson T
Sahl JW
Hepp CM
Handady K
Hornstra H
Vazquez AJ
Settles E
Mayo MJ
Kaestli M
Williamson CHD
Price EP
Sarovich DS
Cook JM
Wolken SR
Bowen RA
Tuanyok A
Foster JT
Drees KP
Kidd TJ
Bell SC
Currie BJ
Keim P
Citation: PLoS Pathog. 2020 Mar 5;16(3):e1008298. doi: 10.1371/journal.ppat.1008298. eCollection 2020 Mar.
Abstract: Although acute melioidosis is the most common outcome of Burkholderia pseudomallei infection, we have documented a case, P314, where disease severity lessened with time, and the pathogen evolved towards a commensal relationship with the host. In the current study, we used whole-genome sequencing to monitor this long-term symbiotic relationship to better understand B. pseudomallei persistence in P314's sputum despite intensive initial therapeutic regimens. We collected and sequenced 118 B. pseudomallei isolates from P314's airways over a >16-year period, and also sampled the patient's home environment, recovering six closely related B. pseudomallei isolates from the household water system. Using comparative genomics, we identified 126 SNPs in the core genome of the 124 isolates or 162 SNPs/indels when the accessory genome was included. The core SNPs were used to construct a phylogenetic tree, which demonstrated a close relationship between environmental and clinical isolates and detailed within-host evolutionary patterns. The phylogeny had little homoplasy, consistent with a strictly clonal mode of genetic inheritance. Repeated sampling revealed evidence of genetic diversification, but frequent extinctions left only one successful lineage through the first four years and two lineages after that. Overall, the evolution of this population is nonadaptive and best explained by genetic drift. However, some genetic and phenotypic changes are consistent with in situ adaptation. Using a mouse model, P314 isolates caused greatly reduced morbidity and mortality compared to the environmental isolates. Additionally, potentially adaptive phenotypes emerged and included differences in the O-antigen, capsular polysaccharide, motility, and colony morphology. The >13-year co-existence of two long-lived lineages presents interesting hypotheses that can be tested in future studies to provide additional insights into selective pressures, niche differentiation, and microbial adaptation. This unusual melioidosis case presents a rare example of the evolutionary progression towards commensalism by a highly virulent pathogen within a single human host.
Click to open Pubmed Article: https://www.ezpdhcs.nt.gov.au/login?url=https://www.ncbi.nlm.nih.gov/pubmed/32134991
Journal title: PLoS pathogens
Volume: 16
Pages: e1008298
Publication Date: 2020
Type: Case Reports
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
URI: https://hdl.handle.net/10137/11428
DOI: 10.1371/journal.ppat.1008298
e1008298
Orcid: 0000-0003-3696-041X
0000-0002-0612-3648
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0000-0002-8878-8837
0000-0003-0089-5820
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