Pathogen & Microbiome Institute, Northern Arizona University, Flagstaff, Arizona, United States of America.
School of Informatics, Computing, and Cyber Systems, Northern Arizona University, Flagstaff, Arizona, United States of America.
PLoS Pathog. 2020 Mar 5;16(3):e1008298. doi: 10.1371/journal.ppat.1008298. eCollection 2020 Mar.
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.
尽管急性类鼻疽是伯克霍尔德菌感染的最常见结果，但我们已经记录了一个病例 P314，其疾病严重程度随着时间的推移而减轻，病原体与宿主之间的关系也朝着共生关系演变。在目前的研究中，我们使用全基因组测序来监测这种长期共生关系，以更好地了解尽管进行了强化初始治疗方案，但伯克霍尔德菌在 P314 的痰液中持续存在的原因。我们从 P314 的气道中收集并测序了 118 株伯克霍尔德菌分离株，时间超过 16 年，并对患者的家庭环境进行了采样，从家庭供水系统中回收了 6 株密切相关的伯克霍尔德菌分离株。使用比较基因组学，我们在 124 个分离株的核心基因组中鉴定出 126 个 SNP，在包含辅助基因组时鉴定出 162 个 SNP/插入缺失。核心 SNP 用于构建系统发育树，该树显示了环境和临床分离株之间的密切关系，并详细描述了宿主内的进化模式。该系统发育树很少有同形性，与严格的克隆遗传方式一致。重复采样显示出遗传多样化的证据，但频繁的灭绝使前四年只有一个成功的谱系，此后只有两个谱系。总体而言，该种群的进化是非适应性的，最好用遗传漂变来解释。然而，一些遗传和表型变化与原位适应一致。使用小鼠模型，与环境分离株相比，P314 分离株引起的发病率和死亡率大大降低。此外，还出现了潜在的适应性表型，包括 O 抗原、荚膜多糖、运动性和菌落形态的差异。两个长寿命谱系共存超过 13 年，提出了有趣的假设，可以在未来的研究中进行测试，以提供对选择压力、生态位分化和微生物适应的额外见解。这种不寻常的类鼻疽病例为高度致病病原体在单个人类宿主中向共生关系进化提供了一个罕见的例子。
