Format

Send to

Choose Destination
J Invest Dermatol. 2015 Nov;135(11):2714-2722. doi: 10.1038/jid.2015.254. Epub 2015 Jul 2.

IsaB Inhibits Autophagic Flux to Promote Host Transmission of Methicillin-Resistant Staphylococcus aureus.

Author information

1
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Division of Dermatology, Department of Medicine, University of California, San Diego, San Diego, California, USA.
2
Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
3
Cardiovascular Medical Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan.
4
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
5
Division of Dermatology, Department of Medicine, University of California, San Diego, San Diego, California, USA; VA San Diego Healthcare Center, San Diego, California, USA.
6
Division of Dermatology, Department of Medicine, University of California, San Diego, San Diego, California, USA. Electronic address: chunming@ucsd.edu.

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a major nosocomial pathogen that is widespread in both health-care facilities and in the community at large, as a result of direct host-to-host transmission. Several virulence factors are associated with pathogen transmission to naive hosts. Immunodominant surface antigen B (IsaB) is a virulence factor that helps Staphylococcus aureus to evade the host defense system. However, the mechanism of IsaB on host transmissibility remains unclear. We found that IsaB expression was elevated in transmissible MRSA. Wild-type isaB strains inhibited autophagic flux to promote bacterial survival and elicit inflammation in THP-1 cells and mouse skin. MRSA isolates with increased IsaB expression showed decreased autophagic flux, and the MRSA isolate with the lowest IsaB expression showed increased autophagic flux. In addition, recombinant IsaB rescued the virulence of the isaB deletion strain and increased the group A streptococcus (GAS) virulence in vivo. Together, these results reveal that IsaB diminishes autophagic flux, thereby allowing MRSA to evade host degradation. These findings suggest that IsaB is a suitable target for preventing or treating MRSA infection.

PMID:
26134948
PMCID:
PMC4641007
DOI:
10.1038/jid.2015.254
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center