Emergence of host-adapted Salmonella Enteritidis through rapid evolution in an immunocompromised host
Emergence of host-adapted Salmonella Enteritidis through rapid evolution in an immunocompromised host
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DOI：
10.1038/nmicrobiol.2015.23
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发表时间：
2016-03-01
影响因子：
28.3
通讯作者：
Kingsley, Robert A.
中科院分区：
文献类型：
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作者：
Klemm, Elizabeth J.;Gkrania-Klotsas, Effrossyni;Kingsley, Robert A.
宿主适应是导致新的细菌、病毒和寄生虫病原体出现的关键因素。许多病原体被认为是混杂的，因为它们在一系列宿主物种中引起疾病，而其他病原体是宿主适应的，感染特定宿主(1)。宿主适应有可能发展为宿主限制，即病原体被严格限制于单一宿主物种，并常常伴有更严重的症状。适应宿主和限制宿主的细菌枝从更广泛的宿主混杂物种中进化而来，有时在其专业宿主中针对不同的生态位，例如从粘膜适应到系统生活方式。基因组降解，以基因失活和缺失为标志，是宿主适应的一个关键特征，尽管启动基因组降解的触发因素尚不清楚。在这里，我们表明，慢性系统性非伤寒沙门氏菌感染免疫功能低下的人类患者导致基因组降解靶向基因，是消耗的系统性生活方式。我们提出了一项基于基因组的研究，在一个白细胞介素-12 β 1受体缺乏的个体中，复发性血源性肠沙门氏菌血清型肠炎（S. Enteritidis）感染覆盖了15年，并发展为无症状的慢性感染。感染肠炎沙门氏菌的错配修复基因mutS发生突变，加速了基因组突变率。多个患者分离株的系统发育分析和表型分析为宿主内进化的显著水平提供了证据，这种进化与成功的宿主限制性细菌病原体中存在的基因组变化相似，但在此时间尺度上从未观察到。我们的分析确定了宿主适应的共同途径，并证明免疫功能低下的个体在这一过程中可以发挥作用。
Host adaptation is a key factor contributing to the emergence of new bacterial, viral and parasitic pathogens. Many pathogens are considered promiscuous because they cause disease across a range of host species, while others are host-adapted, infecting particular hosts(1). Host adaptation can potentially progress to host restriction, where the pathogen is strictly limited to a single host species and is frequently associated with more severe symptoms. Host-adapted and host-restricted bacterial clades evolve from within a broader host-promiscuous species and sometimes target different niches within their specialist hosts, such as adapting from a mucosal to a systemic lifestyle. Genome degradation, marked by gene inactivation and deletion, is a key feature of host adaptation, although the triggers initiating genome degradation are not well understood. Here, we show that a chronic systemic non-typhoidal Salmonella infection in an immunocompromised human patient resulted in genome degradation targeting genes that are expendable for a systemic lifestyle. We present a genome-based investigation of a recurrent blood-borne Salmonella enterica serotype Enteritidis (S. Enteritidis) infection covering 15 years in an interleukin-12 beta 1 receptor-deficient individual that developed into an asymptomatic chronic infection. The infecting S. Enteritidis harboured a mutation in the mismatch repair gene mutS that accelerated the genomic mutation rate. Phylogenetic analysis and phenotyping of multiple patient isolates provides evidence for a remarkable level of within-host evolution that parallels genome changes present in successful host-restricted bacterial pathogens but never before observed on this timescale. Our analysis identifies common pathways of host adaptation and demonstrates the role that immunocompromised individuals can play in this process.