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

PeerJ. 2022 Sep 14:10:e14010. doi: 10.7717/peerj.14010. eCollection 2022.

Abstract

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.

Keywords: 5-Methylindole; Aminoglycoside; Antibiotic resistance; Antibiotic tolerance; Gram-positive bacteria; Indole; MRSA; Persister; Staphylococcus aureus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoglycosides / pharmacology
  • Anti-Bacterial Agents / pharmacology
  • Bacteria
  • Escherichia coli
  • Humans
  • Indoles / pharmacology
  • Methicillin-Resistant Staphylococcus aureus*
  • Protein Synthesis Inhibitors
  • Staphylococcus aureus

Substances

  • Aminoglycosides
  • 5-methylindole
  • Anti-Bacterial Agents
  • Indoles
  • Protein Synthesis Inhibitors

Grants and funding

This work was supported by research grants from the Natural Science Foundation of Fujian Province (2019J01278 to Yajuan Chen), the National Natural Science Foundation of China (No. 31972918 to Xinmiao Fu) and the Natural Science Foundation of Fujian Province (No. 2021J02029 to Xinmiao Fu). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.