Capsaicin Protects Mice from Community-Associated Methicillin-Resistant Staphylococcus aureus Pneumonia

Abstract

Background α-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 Findings The 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/Significance Capsaicin 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.

Isorhamnetin Attenuates Staphylococcus aureus-Induced Lung Cell Injury by Inhibiting Alpha-Hemolysin Expression

“…The hemolytic activity of the culture supernatant was determined as described in our previous study [11]. Briefly, S. aureus strains were cultured (37°C, 200 rpm) in TSB supplemented with the indicated concentrations of isorhamnetin and centrifuged at 10,000 ×g for 5 min at the post-exponential phase (OD 600 of 2.5).…”

“…The role of Hla in the pathogenesis of S. aureus is critical, as evident from the fact that mutants lacking Hla display reduced virulence in many animal models of diseases [1,8,13,19]. Some natural compounds identified in our laboratory can attenuate the virulence of S. aureus by inhibiting the expression or antagonizing the pore-forming activity of Hla [11,17,21]. Thus, this protein is a potential target for the development of anti-virulence agents against S. aureus infections.…”

Capsaicin Supplementation Reduces Physical Fatigue and Improves Exercise Performance in Mice

“…It is a naturally occurring phytochemical and is one of the active ingredients of red and chili peppers [1,2]. Peppers have become a popular culinary spice for food throughout the world.…”

Plant Secondary Metabolites in the Battle of Drugs and Drug-Resistant Bacteria: New Heroes or Worse Clones of Antibiotics?

“…Qiu et al reported that a treatment with subinhibitory concentrations of thymol or eugenol decreased the production of α-haemolysin and staphylococcal enterotoxins A and B in both methicillin-sensitive and methicillin-resistant S. aureus isolates [70,118]. Similar results have been obtained that demonstrate reduced S. aureus haemolysis activity and a decrease or even inhibition of the production of staphylococcal α-haemolysin after the treatment of allicin [119], alkaloid capsaicin [120], flavonoids farrerol [121], or epicatechin gallate [122]. Allicin, the major biologically active component of garlic, was shown to effectively neutralize the toxin pneumolysin-a main virulence factor that is produced by S. pneumoniae [123].…”