5-Methylindole kills various bacterial pathogens and potentiates aminoglycoside against methicillin-resistant <i>Staphylococcus aureus</i>

Antibiotic resistance of bacterial pathogens has become a severe threat to human health. To counteract antibiotic resistance, it is of significance to discover new antibiotics and also improve the efficacy of existing antibiotics. Here we show that 5-methylindole, a derivative of the interspecies signaling molecule indole, is able to directly kill various Gram-positive pathogens ( e.g ., Staphylococcus aureus and Enterococcus faecalis ) and also Gram-negative ones ( e.g ., Escherichia coli and Pseudomonas aeruginosa ), with 2-methylindole being less potent. Particularly, 5-methylindole can kill methicillin-resistant S. aureus , multidrug-resistant Klebsiella pneumoniae , Mycobacterium tuberculosis , and antibiotic-tolerant S. aureus persisters. Furthermore, 5-methylindole significantly potentiates aminoglycoside antibiotics, but not fluoroquinolones, killing of S. aureus . In addition, 5-iodoindole also potentiates aminoglycosides. Our findings open a new avenue to develop indole derivatives like 5-methylindole as antibacterial agents or adjuvants of aminoglycoside.