5-Methylindole kills various bacterial pathogens and potentiates aminoglycoside against methicillin-resistant Staphylococcus aureus

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.