Du Wenyin, Chen Sitong, Jiang Rong, Zhou Huiliu, Li Yuehe, Ouyang Dejia, Gong Yajie, Yao Zhenjiang, Ye Xiaohua
Laboratory of Molecular Epidemiology, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China.
BMC Genomics. 2025 Feb 17;26(1):149. doi: 10.1186/s12864-025-11331-4.
Staphylococcus aureus is an important pathogen that can colonize humans and various animals. However, the host-associated determinants of S. aureus remain uncertain, which leads to difficulties in inferring its host species and cross-species transmission. We performed a 3-stage genome-wide association study (discovery, confirming, and validation) to compare genetic variation between pig and human S. aureus, aiming to elucidate the host-specific genetic elements (k-mers).
After 3-stage association analyses, we found a subset of 20 consensus-significant host-associated k-mers, which are significantly overrepresented in a specific host. Surprisingly for host prediction, both the final model with the top 5 k-mers and the simplest model with only the most important k-mer achieved a high classification accuracy of 98%, giving a simple target for predicting host species and cross-species transmission of S. aureus. The final classifier with the top 5 k-mers revealed that 97.5% of S. aureus isolates from livestock-exposed workers were predicted as pig origin, suggesting a high cross-species transmission risk. The time-based phylogeny inferred the cross-species transmission directions, indicating that ST9 can cross-species spread from animals to humans while ST59 can cross-species spread in the opposite direction.
Our findings provide novel insights into host-associated determinants and an accurate model for inferring S. aureus host species and cross-species transmission.
金黄色葡萄球菌是一种重要的病原体，可在人类和各种动物体内定植。然而，金黄色葡萄球菌与宿主相关的决定因素仍不明确，这导致推断其宿主物种和跨物种传播存在困难。我们进行了一项三阶段全基因组关联研究（发现、确认和验证），以比较猪源和人源金黄色葡萄球菌之间的遗传变异，旨在阐明宿主特异性遗传元件（k- 元组）。
经过三阶段关联分析，我们发现了一组20个具有共识意义的宿主相关k- 元组，它们在特定宿主中显著富集。令人惊讶的是，对于宿主预测，前5个k- 元组的最终模型和仅包含最重要k- 元组的最简单模型都达到了98%的高分类准确率，为预测金黄色葡萄球菌的宿主物种和跨物种传播提供了一个简单的指标。前5个k- 元组的最终分类器显示，97.5%来自接触家畜工人的金黄色葡萄球菌分离株被预测为猪源，这表明存在很高的跨物种传播风险。基于时间的系统发育推断了跨物种传播方向，表明ST9可从动物跨物种传播到人类，而ST59可沿相反方向跨物种传播。
我们的研究结果为宿主相关决定因素提供了新的见解，并为推断金黄色葡萄球菌宿主物种和跨物种传播提供了一个准确的模型。
