Sub-inhibitory concentrations of tigecycline could attenuate the virulence of Staphylococcus aureus by inhibiting the product of α-toxin.

Abstract

Staphylococcus aureus (S. aureus) infection is a serious threat to global health. This study aimed to investigate the anti-virulence efficacy of tigecycline against S. aureus. We used highly virulent S. aureus strains SA75 and JP30 to evaluate the effect of tigecycline on virulence, both of them isolated from the clinic. The MIC value of tigecycline against SA75 was 0.125 µg/mL, and that against JP30 was 0.25 µg/mL. Tigecycline did not affect the growth ability of bacteria at 0.015 µg/mL. Thus, subsequent discussions will focus on the effect of antibiotics at the latter subinhibitory concentrations that did not affect growth. First, the sub-MICs of tigecycline not only enhanced the sensitivity of S. aureus to oxidants and human whole blood but also weakened the hemolytic activity and cell adhesion level of S. aureus. Second, it undermined the survival of S. aureus in RAW264.7 and attenuated the macrophage inflammatory response induced by S. aureus. On the contrary, tigecycline decreased the hemolytic activity, as well as the skin abscess formation and bacterial burden in mice. Most importantly, it significantly decreased the expression of hla, hlgB, hlgC, spa, sbi, saeR, sak, tst, and coa genes by RT-qPCR and the protein expression of α-toxin. Altogether, the sub-MICs of tigecycline might be a promising agent to attenuate the virulence of S. aureus and its host immune response by inhibiting the SaeRS two-component system and the product of α-toxin.IMPORTANCEIn this study, the sub-MICs of tigecycline decreased the resistance of S. aureus to oxidants and human whole blood. Moreover, tigecycline weakened the cell adhesion level of S. aureus and skin abscess formation in mice by reducing bacterial burden. Remarkably, tigecycline decreased the hemolytic activity and significantly downregulated the expression of various virulence genes and α-toxin. This research highlighted that the sub-MICs of tigecycline might be a promising agent to attenuate the virulence of S. aureus by inhibiting the product of α-toxin.