Essential Fitness Repertoire of Staphylococcus aureus during Coinfection with Acinetobacter baumannii In Vivo

Staphylococcus aureus represents a major human pathogen that frequently involved in polymicrobial infection, while the prevalence and effect of co-infecting microbes on S. aureus in vivo pathogenesis and fitness essentiality remain largely unknown. In this study, a retrospective surveillance of 1,058 clinical samples revealed diversified multispecies infections that notably predominated by co-infection of S. aureus and Acinetobacter baumannii. A high-density S. aureus transposon mutant library coupled to transposon insertion sequencing (Tn-Seq) further identified a core set of genes enriched in metabolism of inorganic ion, amino acid, and carbohydrate, which are essential for S. aureus in vivo infection and tissue colonization in a murine model of systemic infection. Moreover, co-infection with A. baumannii dramatically altered the fitness determinants for S. aureus in vivo infection, with 49% of the mono-infection fitness genes converted to be non-essential, particularly for the functionality compensation of lysine degradation and DNA repair, as well as additional requirement of factors encoding ATP-binding cassette (ABC) transporter. Together, these data pinpoint a high incidence and clinical relevance of co-infection caused by S. aureus and A. baumannii, and illustrate the importance of studying S. aureus pathogenesis in polymicrobial communities.