AUTHOR=Sun Fengqi , Bian Mengmeng , Li Zhongyan , Lv Boyan , Gao Yuanyuan , Wang Yan , Fu Xinmiao 

TITLE=5-Methylindole Potentiates Aminoglycoside Against Gram-Positive Bacteria Including Staphylococcus aureus Persisters Under Hypoionic Conditions

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2020.00084

DOI=10.3389/fcimb.2020.00084

ISSN=2235-2988

ABSTRACT=<p>Antibiotic resistance/tolerance has become a severe threat to human and animal health. To combat antibiotic-resistant/tolerant bacteria, it is of significance to improve the efficacy of traditional antibiotics. Here we show that indole potentiates tobramycin to kill stationary-phase <italic>Staphylococcus aureus</italic> cells after a short, combined treatment, with its derivative 5-methylindole being the most potent compound tested and with the absence of ions as a prerequisite. Consistently, this combined treatment also kills various types of <italic>S. aureus</italic> persister cells as induced by the protonophore CCCP, nutrient shift, or starvation, as well as methicillin-resistant <italic>S. aureus</italic> (MRSA) cells. Importantly, 5-methylindole potentiates tobramycin killing of <italic>S. aureus</italic> persisters in a mouse acute skin wound model. Furthermore, 5-methylindole facilitates killing of many strains of gram-positive pathogens such as <italic>Staphylococcus epidermidis, Enterococcus faecalis</italic>, and <italic>Streptococcus pyogenes</italic> by aminoglycoside antibiotics, whereas it suppresses the action of aminoglycoside against the gram-negative pathogens <italic>Escherichia coli</italic> and <italic>Shigella flexneri</italic>. In conclusion, our work may pave the way for the development of indole derivatives as adjuvants to potentiate aminoglycosides against gram-positive pathogens.</p>