美国斯坦福大学医学院Denise M. Monack研究团队利用高通量适应性实验，揭示了人类适应性沙门氏菌在应激和感染过程中的特殊脆弱性。相关论文于2024年6月3日发表在《自然-遗传学》杂志上。

研究人员以前所未有的规模对肠炎沙门氏菌进行了高通量功能基因组学研究，研究对象既包括普通沙门氏菌（伤寒沙门氏菌），也包括限制人类感染的沙门氏菌（伤寒杆菌和副伤寒杆菌A）。利用全面的系统生物学方法，研究确定了在感染人类宿主遇到的25种相关压力下，具有血清特异性适存效应的基因网络。

通过实验扰乱这些网络，研究确定了人类适应性沙门氏菌中之前未知的假基因特征。总的来说，这项工作强调了人类限制沙门氏菌编码的特定脆弱性，这些脆弱性与它们的基因组降解有关，并为这种肠道病原体的进化提供了线索。

据悉，肠炎沙门氏菌（Salmonella enterica）由遗传不同的"血清型"（serovars）组成，这些血清型为探索病原体的基因进化基础提供了一个有趣的模型。虽然已经对宿主范围和在人类疾病中表现差异很大的大量沙门氏菌分离株进行了基因组测序，但对不同血清型之间的遗传和表型差异是否存在关联仍知之甚少。

附：英文原文

Title: High-throughput fitness experiments reveal specific vulnerabilities of human-adapted Salmonella during stress and infection

Author: Wang, Benjamin X., Leshchiner, Dmitry, Luo, Lijuan, Tuncel, Miles, Hokamp, Karsten, Hinton, Jay C. D., Monack, Denise M.

Issue&Volume: 2024-06-03

Abstract: Salmonella enterica is comprised of genetically distinct ‘serovars’ that together provide an intriguing model for exploring the genetic basis of pathogen evolution. Although the genomes of numerous Salmonella isolates with broad variations in host range and human disease manifestations have been sequenced, the functional links between genetic and phenotypic differences among these serovars remain poorly understood. Here, we conduct high-throughput functional genomics on both generalist (Typhimurium) and human-restricted (Typhi and Paratyphi A) Salmonella at unprecedented scale in the study of this enteric pathogen. Using a comprehensive systems biology approach, we identify gene networks with serovar-specific fitness effects across 25 host-associated stresses encountered at key stages of human infection. By experimentally perturbing these networks, we characterize previously undescribed pseudogenes in human-adapted Salmonella. Overall, this work highlights specific vulnerabilities encoded within human-restricted Salmonella that are linked to the degradation of their genomes, shedding light into the evolution of this enteric pathogen.

DOI: 10.1038/s41588-024-01779-7

Source: https://www.nature.com/articles/s41588-024-01779-7