These methods disrupt the pathogenesis of bacterial infections without affecting bacterial growth. Therefore, the evolutionary development of resistance may decrease, as most virulence

traits are not essential for bacterial viability. In contrast, antibiotics that kill microbes exert a strong selective pressure, which results in the emergence of drug-resistant Galunisertib strains (Levy et al., 1976). Staphylococcus aureus secretes a number of extracellular virulence factors that contribute to its pathogenicity. Moreover, many recent studies have demonstrated a rapid evolution of virulence in MRSA strains, which may lead to more severe and widespread disease (Holden et al., 2004; Li et al., 2009). Consequently, the clinical therapeutic values of antimicrobial agents selected for the treatment for S. aureus infections are evaluated not only for their respective bactericidal or bacteriostatic activities but also for their effect on virulence factors (Bernardo et al., 2004). On the other hand, virulence factors may potentially serve as targets Selleckchem Y27632 for the development of new drugs. However, previous reports have indicated that mutations

that abolish the expression of only one of S. aureus extracellular virulence factors do not cause a significant decrease in pathogenesis when measured in animal models of disease (O’Reilly et al., 1986; Patel et al., 1987). Nevertheless, there are some exceptions; intranasal infection of mice with hla−S. aureus resulted in substantially less lung injury and inflammation than an infection with hla+S. aureus, and the mortality of mice infected with hla−S. aureus was much lower than that of mice infected with hla+S. aureus (Bubeck Wardenburg et al., 2007; Bartlett et al., 2008). Disruption of

the toxin function by a number of distinct immunization strategies has been shown to provide protection against S. aureus pneumonia (Bubeck Wardenburg & Schneewind, 2008; Ragle & Bubeck Wardenburg, 2009). Targeting virulence factors is a Cyclooxygenase (COX) promising strategy that relies on newly discovered synthetic or natural small organic compounds to inhibit the expression or secretion of virulence factors (Hung et al., 2005; Rasko et al., 2008). Based on our results that IAL in vitro inhibits the production of α-toxin by S. aureus and in vivo protects mice from S. aureus pneumonia, the structure of IAL could potentially be used as a basic structure for the development of drug that aimed against S. aureus α-toxin. Use of antivirulence drugs in combination with established or novel antimicrobials is suggested and may extend the life span of these drugs (Cegelski et al., 2008; Paul & Leibovici, 2009). It has been shown that subinhibitory concentrations of β-lactam antibiotics can strongly increase the production of α-toxin, which may aggravate disease (Ohlsen et al., 1998; Worlitzsch et al., 2001). Therefore, the data presented here suggest that IAL is potentially useful for the treatment for S.