Abstract
Backgroundα-toxin is one of the major virulence factors secreted by most Staphylococcus aureus strains, which played a central role in the pathogenesis of S. aureus pneumonia. The aim of this study was to investigate the impact of capsaicin on the production of α-toxin by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strain USA 300 and to further assess its performance in the treatment of CA-MRSA pneumonia in a mouse model.Methodology/Principal FindingsThe in vitro effects of capsaicin on α-toxin production by S. aureus USA 300 were determined using hemolysis, western blot, and real-time RT-PCR assays. The influence of capsaicin on the α-toxin-mediated injury of human alveolar epithelial cells was determined using viability and cytotoxicity assays. Mice were infected intranasally with S. aureus USA300; the in vivo protective effects of capsaicin against S. aureus pneumonia were assessed by monitoring the mortality, histopathological changes and cytokine levels. Low concentrations of capsaicin substantially decreased the production of α-toxin by S. aureus USA 300 without affecting the bacterial viability. The addition of capsaicin prevented α-toxin-mediated human alveolar cell (A549) injury in co-culture with S. aureus. Furthermore, the in vivo experiments indicated that capsaicin protected mice from CA-MRSA pneumonia caused by strain USA 300.Conclusions/SignificanceCapsaicin inhibits the production of α-toxin by CA-MRSA strain USA 300 in vitro and protects mice from CA-MRSA pneumonia in vivo. However, the results need further confirmation with other CA-MRSA lineages. This study supports the views of anti-virulence as a new antibacterial approach for chemotherapy.
Highlights
Staphylococcus aureus, a ubiquitous and virulent pathogen, causes significant morbidity and mortality from a variety of infectious syndromes ranging from minor skin and soft-tissue infections to life-threatening deep tissue infections [1]
In contrast to health-care-associated methicillin-resistant S. aureus (MRSA) (HA-MRSA) infections, community-associated MRSA (CAMRSA) infections can occur in otherwise healthy individuals [5], suggesting that these bacterial strains have a greater virulence than traditional HA-MRSA strains
These concentrations of capsaicin have no influence on S. aureus growth (Fig. 1B); a drug-free culture supernatant preincubated with 16 mg/ml of capsaicin resulted in no differences in the hemolytic unit (HU) (Data not shown)
Summary
Staphylococcus aureus, a ubiquitous and virulent pathogen, causes significant morbidity and mortality from a variety of infectious syndromes ranging from minor skin and soft-tissue infections to life-threatening deep tissue infections [1]. Over the past few years, MRSA has emerged as an important cause of community-associated infections in both paediatric and adult populations [3,4]. In contrast to health-care-associated MRSA (HA-MRSA) infections, community-associated MRSA (CAMRSA) infections can occur in otherwise healthy individuals [5], suggesting that these bacterial strains have a greater virulence than traditional HA-MRSA strains. This notion was confirmed by data from various animal infection models [6,7] in which prominent CA-MRSA isolates, such as USA300, are the most prevalent CAMRSA strain and account for up to 97% of all CA-MRSA infections [8]. The toxin is known to cause the destruction of a wide-range of host cells, including erythrocytes, epithelial cells, fibroblasts, and monocytes
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