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Background <p><i>Staphylococcus aureus</i> is an important pathogen that can colonize humans and various animals. However, the host-associated determinants of <i>S. aureus</i> 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 <i>S. aureus</i>, aiming to elucidate the host-specific genetic elements (k-mers).</p> Results <p>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 <i>S. aureus</i>. The final classifier with the top 5 k-mers revealed that 97.5% of <i>S. aureus</i> 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.</p> Conclusion <p>Our findings provide novel insights into host-associated determinants and an accurate model for inferring <i>S. aureus</i> host species and cross-species transmission.</p>

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Inferring Staphylococcus aureus host species and cross-species transmission from a genome-based model

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月17日

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  • Wenyin Du,
  • Sitong Chen,
  • Rong Jiang,
  • Huiliu Zhou,
  • Yuehe Li,
  • Dejia Ouyang,
  • Yajie Gong,
  • Zhenjiang Yao,
  • Xiaohua Ye

摘要

Background

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).

Results

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.

Conclusion

Our findings provide novel insights into host-associated determinants and an accurate model for inferring S. aureus host species and cross-species transmission.