Pathogen to commensal: longitudinal within-host population dynamics, evolution, and adaptation during a chronic >16-year Burkholderia pseudomallei infection

Although acute melioidosis is the most common outcome of Burkholderia pseudomallei infection, we have documented a case, P314, where the 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 chronic infection to better understand B. pseudomallei persistence in P314s sputum despite intense and repeated therapeutic regimens. We collected and sequenced 118 B. pseudomallei isolates from P314s airways over a u003e16-year period, and also sampled the patients home environment, recovering six closely related B. pseudomallei isolates from water. 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 single clonal population. 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, resulting in a highly linear topology. Although these extinctions and persistence could be explained by genetic drift, we observe phenotypic changes 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 changed with time and included differences in the O-antigen, capsular polysaccharide, motility, and colony morphology. The u003e13-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 to commensalism by a highly virulent pathogen within a single human host.