Exploring the activity of hydrogen sulphide against dermatophytes

Infections caused by dermatophytes are common but challenging to treat, especially nail infections. Oral treatments can be effective but may cause adverse effects and drug interactions, while topical treatments are often ineffective and can take over a year due to poor penetration of antifungals into the nail plate. Small molecules, such as hydrogen sulphide (H2S) are predicted to penetrate readily into the nail plate, and previous studies have shown that H2S has antifungal properties against plant pathogens. The aim of this study was therefore to test whether H2S has effective antimicrobial activity against microbes that cause nail infections. We found that H2S has strong antimicrobial activity against dermatophytic and non-dermatophytic fungi and some bacteria. The most active form appeared to be H2S, not the anion HS, which was likely due to its faster uptake into cells. H2S was more effective during the germination phase of fungi, possibly because it inhibits cytochrome C oxidase (COX), a crucial enzyme in respiration. The latter process seems particularly important during germination. Additionally, H2S increased reactive oxygen species and caused excessive S sulfhydration of proteins. It is conceivable that these different effects are linked: inhibition of COX leads to leakage of electrons and the subsequent generation of ROS. That, in turn, could result in an increase in oxidation of cysteine residues to sulfenic acid groups that can then react with H2S, resulting in S-sulfhydration of proteins. Transcriptomic studies in Trichophyton rubrum revealed several genes that were up- or downregulated in response to H2S, indicating a stress response. Overall, hydrogen sulphide shows promise as a potential treatment against microbes that can cause nail infections due to its strong antimicrobial activity.