Yang Linghuan, d' Ovidio Loredana, Chen Ruixi, Resendiz-Moctezuma Cristina, Qian Chenhao, Wiedmann Martin, Orsi Renato H
Department of Food Science, Cornell University, Ithaca, New York, USA.
Food Research Center, Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
Microbiol Spectr. 2025 Sep 2;13(9):e0133625. doi: 10.1128/spectrum.01336-25. Epub 2025 Jul 18.
Dublin is an enteric pathogen that has adapted to cattle as its primary host. It rarely causes foodborne outbreaks but is frequently associated with invasive and severe infections in humans. However, the underlying mechanisms responsible for its enhanced virulence in humans remain unknown. In this study, we conducted comparative genomic analyses and an oxidative stress assay focusing on Dublin isolates classified, in a previous study, as human-associated (HA) or non-human-associated (NHA). We found that 82.5% and 20% of the isolates in the NHA group harbor premature stop codons (PMSCs) in and , respectively, with disrupted possibly contributing to attenuated virulence in these isolates. PMSCs in and were found in 100% of isolates in the HA group and in 62.5% and 60% of isolates in the NHA group, respectively. In addition, 100% and 42.5% of isolates in the HA group harbor PMSCs in and , respectively, with disrupted possibly contributing to an enhanced virulence in these isolates. Moreover, a multidrug resistance plasmid (pVPS18S0911-1-like) was strongly associated with HA isolates, which may allow these isolates to cause prolonged infections leading to increased clinical severity. While an IS transposon inserted within , located between two genes putatively involved in oxidative stress, was observed exclusively among HA isolates, these isolates did not show a significantly different oxidative stress survival to HO as compared to NHA isolates. Finally, the presence of the virulence plasmid and the Vi antigen was not associated with the HA isolates.IMPORTANCE Dublin causes a severe extra-intestinal infection in 64% of human cases with a 3% fatality rate. In this study, we compared the genomes of human-associated (HA) Dublin isolates to non-human-associated (NHA) isolates and identified genetic features associated with the HA or NHA groups, such as single nucleotide polymorphisms in genes putatively involved in virulence, presence of antimicrobial resistance genes in an HA-associated plasmid, and an insertion element between two genes putatively involved in oxidative stress. HA and NHA isolates showed, however, no differences in an oxidative stress survival assay. Overall, this study identified novel genetic features putatively involved in the virulence diversity within Dublin throughout a combination of phylogenetic analysis, genome-wide association study, and phenotypic assessment, providing insights for future studies to elucidate the mechanisms leading to the severe human infections typically caused by Dublin.
都柏林沙门氏菌是一种肠道病原体，已适应以牛作为其主要宿主。它很少引起食源性疾病暴发，但经常与人类的侵袭性和严重感染有关。然而，其在人类中增强毒力的潜在机制仍不清楚。在本研究中，我们进行了比较基因组分析和氧化应激试验，重点关注在先前研究中被分类为人类相关（HA）或非人类相关（NHA）的都柏林沙门氏菌分离株。我们发现，NHA组中分别有82.5%和20%的分离株在 和 中含有过早终止密码子（PMSC）， 的破坏可能导致这些分离株的毒力减弱。在HA组的所有分离株以及NHA组62.5%和60%的分离株中均发现了 和 中的PMSC。此外，HA组中分别有100%和42.5%的分离株在 和 中含有PMSC， 的破坏可能导致这些分离株的毒力增强。此外，一种多药耐药质粒（pVPS18S0911-1样）与HA分离株密切相关，这可能使这些分离株能够引起持续感染，导致临床严重程度增加。虽然在HA分离株中仅观察到一个插入序列转座子插入到 内，该区域位于两个可能参与氧化应激的基因之间，但与NHA分离株相比，这些分离株在氧化应激下的存活能力没有显著差异。最后， 毒力质粒和Vi抗原的存在与HA分离株无关。
都柏林沙门氏菌在64%的人类病例中引起严重的肠道外感染，死亡率为3%。在本研究中，我们比较了人类相关（HA）都柏林沙门氏菌分离株与非人类相关（NHA）分离株的基因组，并确定了与HA或NHA组相关的遗传特征，例如可能参与毒力的基因中的单核苷酸多态性、HA相关质粒中抗菌抗性基因的存在以及两个可能参与氧化应激的基因之间的插入元件。然而，HA和NHA分离株在氧化应激存活试验中没有差异。总体而言，本研究通过系统发育分析、全基因组关联研究和表型评估相结合，确定了都柏林沙门氏菌中毒力多样性可能涉及的新遗传特征，为未来阐明导致都柏林沙门氏菌通常引起的严重人类感染机制的研究提供了见解。
