Role of the ESAT-6 secretion system in virulence of the emerging community-associated Staphylococcus aureus lineage ST398.
Novel Staphylococcus aureus clones continue to emerge that cause infections in otherwise healthy people. One example is the sequence type (ST) 398 lineage, which we show here is increasing in importance as a significant cause of community-associated (CA) human infections in China. We have a profound lack of understanding about what determines the considerable virulence potential of such newly emerging clones. Information about the contribution to virulence of the more recently discovered ESAT-6 secretion system (ESS) has remained particularly scarce. The Chinese ST398 isolates exhibited significantly increased expression of ESS genes as compared to predominant hospital-associated clones, which we found is likely due to increased expression of the accessory gene regulator (Agr) system and control of ESS by Agr. Importantly, deletion of essB in ST398 resulted in significantly reduced resistance to neutrophil killing and decreased virulence in murine skin and blood infection models. Our results demonstrate a key function of ESS in promoting virulence and mechanisms of resistance to innate host defense in an important emerging CA-S. aureus lineage. They suggest that ESS has a so far underestimated role in promoting aggressive virulence and epidemiological success of S. aureus.
Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.
Yanan
Y
Wang
Institute of Analytical Chemistry and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
Mo
M
Hu
Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.
Qian
Q
Liu
Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.
Juanxiu
J
Qin
Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.
Yingxin
Y
Dai
Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.
Lei
L
He
Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.
Tianming
T
Li
Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.
Bing
B
Zheng
Institute of Analytical Chemistry and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
Fan
F
Zhou
Institute of Analytical Chemistry and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
Kaiwen
K
Yu
Division of Gastroenterology &Hepatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University; Shanghai Institute of Digestive Disease, Shanghai 200127, China.
Jingyuan
J
Fang
Institute of Analytical Chemistry and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
Xiaoyun
X
Liu
Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, MD 20892, USA.
Michael
M
Otto
Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.
Min
M
Li
D000818:Animals; D016470:Bacteremia / Q000382:microbiology / Q000473:pathology; D058947:Bacterial Secretion Systems / Q000378:metabolism*; D002681:China; D017714:Community-Acquired Infections / Q000382:microbiology*; D004195:Disease Models, Animal; D017353:Gene Deletion; D006801:Humans; D051379:Mice; D021381:Protein Transport; D013203:Staphylococcal Infections / Q000382:microbiology*; D013207:Staphylococcal Skin Infections / Q000382:microbiology / Q000473:pathology; D013211:Staphylococcus aureus / Q000472:pathogenicity*; D014774:Virulence; D037521:Virulence Factors / Q000378:metabolism*
D058947:Bacterial Secretion Systems; D037521:Virulence Factors