Essential Fitness Repertoire of Staphylococcus aureus during Co-infection with Acinetobacter baumannii .
Gang Li, Wei Shen, Yali Gong, Ming Li, Xiaocai Rao, Qian Liu, Yanlan Yu, Jing Zhou, Keting Zhu, Mengmeng Yuan, Weilong Shang, Yi Yang, Shuguang Lu, Jing Wang, Yan Zhao
Author Information
Gang Li: Department of Microbiology, College of Basic Medical Sciences, Army Medical University, Chongqing, China.
Wei Shen: Institute for Viral Hepatitis, Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Yali Gong: State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Key Laboratory for Proteomics Disease, Institute of Burn Research, Southwest Hospital, Army Medical University, Chongqing, China.
Ming Li: Department of Microbiology, College of Basic Medical Sciences, Army Medical University, Chongqing, China.
Xiaocai Rao: Department of Microbiology, College of Basic Medical Sciences, Army Medical University, Chongqing, China.
Qian Liu: Department of Laboratory Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. ORCID
Yanlan Yu: Department of Dermatology, Southwest Hospital, Army Medical University, Chongqing, China.
Jing Zhou: Department of Microbiology, College of Basic Medical Sciences, Army Medical University, Chongqing, China.
Keting Zhu: Department of Emergency, the Second Affiliated Hospital of Army Medical University, Chongqing, China.
Mengmeng Yuan: Department of Microbiology, College of Basic Medical Sciences, Army Medical University, Chongqing, China.
Weilong Shang: Department of Microbiology, College of Basic Medical Sciences, Army Medical University, Chongqing, China.
Yi Yang: Department of Microbiology, College of Basic Medical Sciences, Army Medical University, Chongqing, China.
Shuguang Lu: Department of Microbiology, College of Basic Medical Sciences, Army Medical University, Chongqing, China. ORCID
Jing Wang: Department of Microbiology, College of Basic Medical Sciences, Army Medical University, Chongqing, China.
Yan Zhao: Department of Microbiology, College of Basic Medical Sciences, Army Medical University, Chongqing, China.
Staphylococcus aureus represents a major human pathogen that is frequently involved in polymicrobial infections. However, the prevalence and role of co-infectious microbes on the pathogenesis and fitness essentiality of S. aureus remain largely unknown. In this study, we firstly performed a retrospective surveillance of 760 clinical samples and revealed a notable predominance of co-infection with S. aureus and Acinetobacter baumannii. The 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 ions, amino acids, and carbohydrates, which are essential for infection and tissue colonization of S. aureus in the murine systemic infection model. Notably, we revealed a differential requirement of fitness factors for S. aureus in tissue-specific (liver and kidney) and infection-type-specific manner (mono- and co-infection). Co-infection with A. baumannii dramatically altered the fitness requirements of S. aureus ; 49% of the mono-infection fitness genes in S. aureus strain Newman were converted to non-essential, and the functionality of ATP-binding cassette (ABC) transporters was significantly elicited during co-infection. Furthermore, the number of genes essential during co-infection (503) outnumbers the genes essential during mono-infection (362). In addition, the roles of 3 infection-type-specific genes in S. aureus during mono-infection or co-infection with A. baumannii were validated with competitive experiments . Our data indicated a high incidence and clinical relevance of S. aureus and A. baumannii co-infection, and provided novel insights into establishing antimicrobial regimens to control co-infections. Polymicrobial infections are widespread in clinical settings, which potentially correlate with increased infection severity and poor clinical outcomes. Staphylococcus aureus is a formidable human pathogen that causes a variety of diseases in polymicrobial nature. Co-infection and interaction of S. aureus have been described with limited pathogens, mainly including Pseudomonas aeruginosa, Candida albicans, and influenza A virus. Thus far, the prevalence and role of co-infectious microbes on the pathogenesis and fitness essentiality of S. aureus remain largely unknown. Understanding the polymicrobial composition and interaction, from a community and genome-wide perspective, is thus crucial to shed light on S. aureus pathogenesis strategy. Here, our findings demonstrated, for the first time, that a high incidence rate and clinical relevance of co-infection was caused by S. aureus and Acinetobacter baumannii, illustrating the importance of polymicrobial nature in investigating S. aureus pathogenesis. The infection-type-specific genes likely serve as potential therapeutic targets to control S. aureus infections, either in mono- or co-infection situation, providing novel insights into the development of antimicrobial regimens to control co-infections.
