Abstract
Staphylococcus aureus causes various diseases including skin and soft tissue infections, pneumonia, gastroenteritis, and sepsis. Antibiotic-resistant S. aureus such as methicillin-resistant S. aureus (MRSA) and multidrug-resistant S. aureus is a serious threat in healthcare-associated settings and in the communities. In this study, we investigated the effects of short-chain fatty acids, metabolites produced by commensal bacteria, on the growth of S. aureus both in vitro and in vivo. Sodium propionate (NaP) most potently inhibited the growth of MRSA and multidrug-resistant clinical isolates. Of note, only NaP, but not sodium acetate (NaA) or sodium butyrate (NaB), ameliorated MRSA skin infection, significantly lowering bacterial load, excessive cytokine production, and the size and weight of abscesses approximately by twofold. In addition, interestingly, S. aureus deficient of lipoteichoic acids (LTA) or wall teichoic acids (WTA), which are important in bacterial physiology and antimicrobial susceptibility, was more susceptible to NaP than the wild-type. Furthermore, S. aureus deficient of D-alanine motifs common in LTA and WTA was more susceptible to NaP, its growth being almost completely inhibited. Concordantly, MRSA treated with an inhibitor of D-alanylation on LTA and WTA was more susceptible to NaP, and co-treatment of NaP and a D-alanylation inhibitor further decreased the pathology of MRSA skin infection. Collectively, these results demonstrate that NaP ameliorates MRSA skin infection by attenuating the growth of S. aureus, and suggest an alternative combination treatment strategy against S. aureus infection.
Highlights
Staphylococcus aureus, which frequently colonizes humans, is a major pathogen that causes various diseases including skin and soft tissue infections, pneumonia, and gastroenteritis, and the most frequent bacterium associated with sepsis (Lowy, 1998; Alberti et al, 2002)
When the morphology of S. aureus in the presence or absence of NaP was analyzed with scanning electron microscopy, S. aureus treated with NaP showed no morphological differences compared to non-treated (NT) S. aureus (Supplementary Figure S2)
When the fractional inhibitory concentration index (FICI) (Tascini et al, 2000) was calculated, NaP and AMSA had partial synergy (FICI = 0.6). These results demonstrate that D-alanine residues on lipoteichoic acids (LTA) and wall teichoic acids (WTA) are important in modulating the susceptibility of methicillinresistant S. aureus (MRSA) to NaP
Summary
Staphylococcus aureus, which frequently colonizes humans, is a major pathogen that causes various diseases including skin and soft tissue infections, pneumonia, and gastroenteritis, and the most frequent bacterium associated with sepsis (Lowy, 1998; Alberti et al, 2002). Skin and soft tissue infections represent approximately 90% of S. aureus infections and can lead to the spread of S. aureus to other parts of the body, often resulting in serious diseases such as bacteremia or Propionate Ameliorates MRSA Skin Infection pneumonia (DeLeo et al, 2010). S. aureus is especially adept at acquiring antibiotic resistance. Resistance to new classes of antibiotics (Ventola, 2015) is emphasizing the limited treatment options. Since there is no vaccine available to prevent S. aureus infection (Giersing et al, 2016), a novel strategy to combat antibioticresistant infection is needed
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