Researchers from the Singapore-MIT Alliance for Research and Technology (SMART) find that exposing bacteria to hydrogen sulfide can increase antimicrobial sensitivity and reverse antimicrobial resistance in bacterial that do not produce it.
Autimicrobial resistance is a growing and deeply concerning threat to public health, with the WHO projecting an estimated 10 million deaths each year from drug-resistant diseases by 2050 if no action is taken.
A team of researchers from the Singapore-MIT Alliance for Research and Technology (SMART) have discovered a novel way to reverse acquired antibiotic resistance in some bacteria using hydrogen sulfide (H2S).
H2S, produced endogenously, has been shown to render multiple bacterial species tolerant to oxidative stress and various classes of antibiotics. It was proposed that H2S production was a universal defence mechanism in bacteria against antibiotics, although this assumed that all bacteria produced H2S.
Researchers at SMART’s Antimicrobial Resistance (AMR) Interdisciplinary Research Group (IRG) investigated the effects of exogenous H2S on Acinetobacter baumannii, an antibiotic-resistant pathogen that does not produce H2S internally. A. baumannii is a critically important pathogen for which therapeutic options are becoming increasingly limited, with isolates now displaying resistance to last resort drug including colistin.
Their study, “Hydrogen sulfide sensitises Acinetobacter baumanii to killing by antibiotics” was published in Frontiers in Microbiology and was supported by the Singapore National Medical Research Council’s Young Investigator Grant. “This is a very exciting discovery because we are the first to show that H2S can, in fact, improve sensitivity to antibiotics and even reverse antibiotic resistance in bacteria that do not naturally produce the agent,” said Dr Wilfried Moreira, the principal investigator at SMART’s AMR IRG.
While the study focused on the effects of exogenous H2S on A. baumannii, the scientists believe the results will be mimicked in all bacteria that do not naturally produce H2S.
“Acinetobacter baumannii is a critically important antibiotic-resistant pathogen that poses a huge threat to human health,” added Say Yong Ng, lead author of the paper and Laboratory Technologist at SMART AMR. “Our research has found a way to make the deadly bacteria and others like it more sensitive to antibiotics and can provide a breakthrough in treating many drug-resistant infections.”
The team plans to conduct further studies to validate these exciting findings in pre-clinical models of infection, as well as extending them to other bacteria that do not produce H2S. As H2S-releasing molecules have already been developed for a wide range of clinical uses, their future as antibiotic-resistance potentiators and resistance-reversion agents appears bright.