H₂S mediates interbacterial communication through the air reverting intrinsic antibiotic resistance

Abstract

Hydrogen sulfide, a gas classically considered as a by-product of cellular metabolism, is today recognized as a crucial gasotransmitter in Eukaryotes. Moreover, most bacteria harbor the eukaryotic orthologous genes for H2S synthesis, and these genes have been linked to different metabolic pathways.Some bacteria, however, produce high amounts of H2S in their extracellular space, a characteristic classically used for identification purposes. This is the case of Salmonella Typhimurium, which produces H2S by its phsABC operon. Here we show that extracellular release of H2S by S. Typhimurium is solely dependent on its phsABC operon. Furthermore, we show that S. Typhimurium and other H2S-producing bacteria can interact with physically distant bacteria through H2S production. We demonstrate how H2S can revert intrinsic cephalosporin resistance of Enterococccus faecalis and Enterococcus faecium to complete susceptibility. This study constitutes a significant step in the study of bacterial interplay and niche competition. Furthermore, as H2S releasing drugs have already been designed, our results open the way to future therapeutic alternatives for the treatment of infections caused by enterococci, multiresistant pathogens for which no treatments are clinically available.Author SummaryIt has been known for decades that bacteria can communicate with each other through the diffusion of metabolites in the media. However, the capacity of a bacterium to interact with other physically distant cell is a recent discovery of the 21st century. In this work we show how some well-studied bacteria, as it is Salmonella spp., interacts with other bacteria thanks to the compound hydrogen sulfide (H2S) that they produce and release to the environment.In our study we have designed novel techniques that allow us to study the interaction between two bacteria, and we have seen that Salmonella is able to affect other species that is even 1 cm away, i.e., a distance corresponding to 10.0000 times its own size.What is more astonishing is that Enterococcus, when exposed to the H2S, is dramatically becomes susceptible to many antibiotics, to which it is supposed to be naturally resistant. Enterococcus spp. are responsible for life-threatening infections in hospitals worldwide. Thus, our observations reveal that bacteria can communicate through the air with H2S, and that this molecule can make bacteria that are highly resistant to antibiotics susceptible to antibiotics, making untreatable infections treatable with current antibiotics.

Reducing bacterial antibiotic resistance by targeting bacterial metabolic pathways and disrupting RND efflux pump activity

“…Metabolites in high concentrations increase bacterial antibiotic resistance. Metabolites such as indole, ammonia, nitric oxide, and hydrogen sulfide can amplify antibiotic resistance [9]. However, carbon in higher amounts eradicates more pathogenic bacteria by increasing antibiotic sensitivity.…”