Microbes and Food Safety, Quadram Institute Bioscience, Norwich, United Kingdom.
Centre for Microbial Interactions, Norwich Research Park, Norwich, United Kingdom.
PLoS Pathog. 2024 Oct 31;20(10):e1012679. doi: 10.1371/journal.ppat.1012679. eCollection 2024 Oct.
Salmonella enterica serovar Agona (S. Agona) has been increasingly recognised as a prominent cause of gastroenteritis. This serovar is a strong biofilm former that can undergo genome rearrangement and enter a viable but non-culturable state whilst remaining metabolically active. Similar strategies are employed by S. Typhi, the cause of typhoid fever, during human infection, which are believed to assist with the transition from acute infection to chronic carriage. Here we report S. Agona's ability to persist in people and examine factors that might be contributing to chronic carriage. A review of 2233 S. Agona isolates from UK infections (2004-2020) and associated carriage was undertaken, in which 1155 had short-read sequencing data available. A subset of 207 isolates was selected from different stages of acute and persistent infections within individual patients. The subset underwent long-read sequencing and genome structure (GS) analysis, as well as phenotyping assays including carbon source utilisation and biofilm formation. Associations between genotypes and phenotypes were investigated to compare acute infections to those which progress to chronic. GS analysis revealed the conserved arrangement GS1.0 in 195 isolates, and 8 additional GSs in 12 isolates. These rearranged isolates were typically associated with early, convalescent carriage (3 weeks- 3 months). We also identified an increase in SNP variation during this period of infection. We believe this increase in genome-scale and SNP variation reflects a population expansion after acute S. Agona infection, potentially reflecting an immune evasion mechanism which enables persistent infection to become established.
肠炎沙门氏菌血清型阿贡纳（S. Agona）已被越来越多地认为是胃肠炎的主要原因。该血清型是一种强生物膜形成者，能够进行基因组重排并进入存活但非可培养状态，同时保持代谢活性。类似的策略被伤寒沙门氏菌（引起伤寒的病原体）在人类感染期间采用，据信这些策略有助于从急性感染向慢性携带的转变。在这里，我们报告了 S. Agona 在人体内的持续存在，并研究了可能导致慢性携带的因素。对英国 2004 年至 2020 年期间 2233 例感染 S. Agona 的病例（2233 例）和相关携带情况进行了回顾性分析，其中 1155 例有短读测序数据。从个体患者的急性和持续性感染的不同阶段选择了 207 株分离物的亚组。对该亚组进行了长读测序和基因组结构（GS）分析，以及表型分析，包括碳源利用和生物膜形成。研究了基因型和表型之间的相关性，以比较急性感染和进展为慢性感染的情况。GS 分析显示，195 株分离物具有保守的 GS1.0 排列，12 株分离物具有 8 种额外的 GS。这些重排的分离物通常与早期恢复期携带（3 周到 3 个月）有关。我们还发现在此感染期间 SNP 变异增加。我们认为，这种基因组规模和 SNP 变异的增加反映了急性 S. Agona 感染后种群的扩张，这可能反映了一种免疫逃避机制，使持续感染得以建立。
