Virulence determinants associated with the Asian community-associated methicillin-resistant Staphylococcus aureus lineage ST59.
Understanding virulence is vital for the development of novel therapeutics to target infections with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), which cause an ongoing epidemic in the United States and are on a global rise. However, what defines virulence particularly of global CA-MRSA lineages is poorly understood. Threatening a vast population, the predominant Asian CA-MRSA lineage ST59 is of major epidemiological importance. However, there have been no molecular analyses using defined virulence gene deletion mutants in that lineage as of yet. Here, we compared virulence in skin, lung, and blood infection models of ST59 CA-MRSA isolates with geographically matched hospital-associated MRSA isolates. We selected a representative ST59 CA-MRSA isolate based on toxin expression and virulence characteristics, and produced isogenic gene deletion mutants of important CA-MRSA virulence determinants (α-toxin, PSM α, Agr) in that isolate for in-vitro and in-vivo analyses. Our results demonstrate strongly enhanced virulence of ST59 CA-MRSA over hospital-associated lineages, supporting the notion that enhanced virulence is characteristic for CA-MRSA. Furthermore, they show strong and significant contribution of Agr, α-toxin, and PSMα to pathogenesis of ST59 CA-MRSA skin, lung, and blood infection, emphasizing the value of drug development efforts targeted toward those virulence determinants.
Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Min
M
Li
Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Yingxin
Y
Dai
Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.|Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, Maryland, USA.
Yuanjun
Y
Zhu
Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, Maryland, USA.
Chih-Lung
CL
Fu
Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, Maryland, USA.
Vee Y
VY
Tan
Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Yanan
Y
Wang
Department of Laboratory Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Xing
X
Wang
Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Xufen
X
Hong
Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Qian
Q
Liu
Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Tianming
T
Li
Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Juanxiu
J
Qin
Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Xiaowei
X
Ma
Department of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Institute of Digestive Disease, Shanghai Jiaotong University, Shanghai, China.
Jingyuan
J
Fang
Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, Maryland, USA.
Michael
M
Otto
D000293:Adolescent; D000818:Animals; D044466:Asian People; D001426:Bacterial Proteins / Q000235:genetics; D001427:Bacterial Toxins / Q000235:genetics; D017714:Community-Acquired Infections / Q000453:epidemiology / Q000382:microbiology*; D005260:Female; D006460:Hemolysin Proteins / Q000235:genetics; D006801:Humans; D007049:Iatrogenic Disease / Q000453:epidemiology; D008168:Lung / Q000276:immunology* / Q000382:microbiology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000472:pathogenicity / Q000502:physiology*; D051379:Mice; D008812:Mice, Hairless; D008807:Mice, Inbred BALB C; D000074041:Microorganisms, Genetically-Modified; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology; D017384:Sequence Deletion / Q000235:genetics; D012867:Skin / Q000276:immunology* / Q000382:microbiology; D013203:Staphylococcal Infections / Q000453:epidemiology / Q000382:microbiology*; D015534:Trans-Activators / Q000235:genetics; D014774:Virulence / Q000235:genetics*
C095698:Agr protein, Staphylococcus aureus; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D015534:Trans-Activators; C021091:staphylococcal alpha-toxin; C025971:staphylococcal delta toxin