Antibiotics rendered useless by the notorious methicillin-resistant Staphylococcus aureus, (MRSA) may get a second life, thanks to compounds that can restore the bug's susceptibility to antibiotics, according to a new study in mice. The compounds have no antimicrobial activity on their own, but become lethal when combined with existing antibiotics, offering a potential combination strategy against MRSA. MRSA poses a major public health crisis worldwide and is the second leading cause of death from drug-resistant bacterial infections in the U.S. The bacteria have grown resistant to the entire class of β-lactam antibiotics, which includes penicillin and methicillin, creating an urgent need to develop new drugs or, alternatively, boost the efficacy of existing ones. Here, Sang Ho Lee and colleagues conducted a drug screen for inhibitors of wall teichoic acid, a major structural component of the bacterial cell wall that is thought to buffer MRSA against the antimicrobial effects of β-lactams. The researchers identified two synthetic compounds, which they named tarocin A and tarocin B, that block an enzyme that kickstarts wall teichoic acid production. In culture, the compounds on their own had no effect on MRSA growth, but when paired with β-lactams, killed various clinical strains of MRSA. Whereas mice succumbed to MRSA infection when treated with either tarocin or β-lactam alone, animals treated with both drugs showed markedly reduced infection and improved survival. The researchers say that with further development, tarocins may offer a new class of adjuvants for reviving β-lactam antibiotics' efficacy against MRSA.
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Science Translational Medicine