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Significance The dissemination of antibiotic resistance in pathogenic bacteria is remarkable, and antivirulence agents with novel mechanisms of action could lead to innovative therapeutic concepts. The simultaneous suppression of multiple virulence factors or pathways using small-molecule compounds is an attractive approach to reducing the virulence ofStaphylococcus aureus and may offer promising therapeutic potential in combating multidrug-resistant bacteria such as methicillin-resistantS. aureus . Here we describe a conceptual breakthrough in applying chemical genetics to probe for small-molecule compounds that will suppress the expression of multiple virulence factors inS. aureus simultaneously. Compound M21 has the ability to reverse virulentS. aureus to a nonvirulent state, as demonstrated in a mouse model of infection.

Suppression of Staphylococcus aureus virulence by a small-molecule compound