Commensal Staphylococcus aureus Provokes Immunity to Protect against Skin Infection of Methicillin-Resistant Staphylococcus aureus.

John-Jackson Yang,Ming-Shan Kao,Chun-Ming Huang,Bin-Hao Chiou,Ting-Wei Chang,Hsin-Jou Kao,Yong Jiang

doi:10.3390/ijms19051290

Abstract

Unlike USA300, a strain of community-acquired methicillin-resistant Staphylococcus aureus (MRSA), commensal Staphylococcus aureus (S. aureus) bacteria isolated from human skin demonstrated the ability to mediate the glycerol fermentation to produce short-chain fatty acids (SCFAs). Quantitative proteomic analysis of enzymes involved in glycerol fermentation demonstrated that the expression levels of six enzymes, including glycerol-3-phosphate dehydrogenase (GPDH) and phosphoglycerate mutase (PGM), in commensal S. aureus are more than three-fold higher than those in USA300. Western blotting validated the low expression levels of GPDH in USA300, MRSA252 (a strain of hospital-acquired MRSA), and invasive methicillin-susceptible S. aureus (MSSA). In the presence of glycerol, commensal S. aureus effectively suppressed the growth of USA300 in vitro and in vivo. Active immunization of mice with lysates or recombinant α-hemolysin of commensal S. aureus or passive immunization with neutralizing sera provided immune protection against the skin infection of USA300. Our data illustrate for the first time that commensal S. aureus elicits both innate and adaptive immunity via glycerol fermentation and systemic antibody production, respectively, to fight off the skin infection of pathogenic MRSA.

Highlights

Staphylococcus aureus is a Gram-positive bacteria that colonizes the nasal cavity of 20–30% of the human population without causing any apparent disease [1]
To determine if the antibody cross-reactivity offers a protection against USA300 infection, skin wounds in mice immunized with lysates of commensal S. aureus or green fluorescent protein (GFP) were inoculated with USA300 bacteria
Genomic analysis of S. aureus strains has helped to identify a number of virulence factors [21]

Summary

Introduction

Staphylococcus aureus is a Gram-positive bacteria that colonizes the nasal cavity of 20–30% of the human population without causing any apparent disease [1]. Our previous studies demonstrated that human skin commensal bacteria, which can be defined as a part of skin innate immunity, inhibited the growth of USA300, a strain of community-acquired methicillin-resistant S. aureus (MRSA), by fermenting glycerol to release short-chain fatty acids (SCFAs) [6,7,8]. When glycerol was present in the co-culture, only a few USA300 colonies were observed (Figure 1e) These findings suggest that commensal S. aureus mediated glycerol fermentation to interfere with the growth of USA300. To examine whether other commensal S. aureus isolates exhibit anti-USA300 activities similar to one isolate observed, three different colonies of commensal S. aureus isolated from human skin were selected for co-culture with USA300 in the presence or absence of glycerol.

Differential Expression of Enzymes in the Pathway of Glycerol Fermentation

Discussion

Ethics Statement

Mass Spectrometric Label-Free Protein Quantification and Western Blot

Findings

Statistical Analysis