The “Rotten-Egg” Gas That Kills Fungal Pathogens
Hydrogen sulfide gas destroyed nail infection fungi in hours, suggesting a fast, safe new topical treatment.
For millions with stubborn fungal nail infections, help might come from an unlikely source: the stench of rotten eggs.
A joint study from the University of Bath and King’s College London reports that hydrogen sulfide (H₂S) gas wiped out fungal pathogens in the lab within hours, hinting at a faster, safer topical treatment.
Fungal nail infections remain difficult to treat
Fungal nail infections are surprisingly common, affecting up to ~10% of the global population. These infections typically appear as discoloured, thickened or crumbly nails and are particularly troublesome for people with diabetes or poor circulation, where they can increase the risk of foot ulcers or amputations.
Current treatment options are split into two broad categories: oral antifungals, such as terbinafine or itraconazole, and topical treatments that are applied directly to the nail.
“Oral treatments can be effective but may cause adverse effects and drug interactions, while topical treatments only work in about a third of patients due to poor penetration of antifungals into the nail plate,” said the authors of the latest study.
Even the most advanced topical antifungal formulations often achieve cure rates below 20%.
The need for a topical therapy that is fast-acting, safe and capable of reaching fungi deep in the nail motivated the recent study. The team built on earlier findings that small, polar molecules penetrate nails more efficiently than larger conventional drugs.
How the rotten-egg gas attacks fungal cells
The researchers set out to test whether the notorious “rotten-egg” gas, H₂S, could fight the fungi and bacteria that underlie stubborn nail infections. They used sodium hydrogen sulfide as a donor to release controlled amounts of H₂S.
Donor
A donor is a chemical compound that releases another substance; in this case, it “donates” H₂S gas in a controlled way.
Their approach covered both liquid and gaseous deliveries of H₂S across varying pH levels, mimicking the hostile, keratin-rich nail plate environment, testing against various nail-infection microbes.
Gaseous H₂S proved 50–1000x more potent than its liquid form, with just 3–6 hours of exposure to the gas halting fungal growth. H₂S killed the target fungi, including those that were drug-resistant, and also showed selective antibacterial activity, killing Staphylococcus aureus and MRSA.
Mechanistically, H₂S appeared to shut down a key enzyme, cytochrome c oxidase, triggering energy collapse, which led to a surge in reactive oxygen species and chemical modification of fungal proteins.
Transcriptome data revealed that, after H₂S exposure, 96 genes were upregulated and 117 were downregulated in one key fungi, reflecting a massive stress response.
What the rotten-egg findings mean for future fungal therapies
The findings open the possibility of a new class of topical treatments for nail infections. Since H₂S penetrates the nail plate efficiently and kills pathogens rapidly, it could offer a faster, safer alternative to current therapies.
“Thanks to its ability to efficiently reach the site of infection and its novel mode of action, we believe that a topically applied medicine containing H₂S could become a highly effective new treatment for nail infections, which avoids the limitations of current therapies,” said co-corresponding author Dr. Albert Bolhuis, a reader in the Department of Life Sciences at the University of Bath.
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This approach may be especially valuable for the elderly or people with diabetes, who often cannot tolerate oral antifungals.
“Our research lays the foundation for a compelling alternative to existing treatments, with the potential to improve outcomes for patients suffering from persistent and drug-resistant fungal nail infections,” added Bolhuis.
However, the work to date is entirely in vitro, and a topical formulation must be developed that controls gas release and mitigates odor. The rotten-egg smell could hinder acceptability unless addressed. In vivo safety and efficacy also must be confirmed in animal and human trials.
“We are looking forward to translating these findings into an innovative topical product that can treat nail infection,” said co-corresponding author Prof. Stuart Jones, the director of the Centre for Pharmaceutical Medicine Research at Kings College London.
If further testing succeeds, this could be one “rotten-egg” smell that’s actually worth bottling.
Reference: Ho FKH, Al-Tabtabai A, Nasereddin SM, et al. Antimicrobial effects and mechanisms of hydrogen sulphide against nail pathogens. Sci Rep. 2025;15(1):38241. doi: 10.1038/s41598-025-22062-7
This article is a rework of a press release issued by the University of Bath. Material has been edited for length and content.
