The tell-tale smell of rotten eggs is often a sign that sulphur is at work. Sulphur is a key element in proteins such as keratin, which makes hair and nails tough, and used in agriculture to make fertilisers.
Researchers at UCD Conway Institute in University College Dublin have shown for the first time that the yeast, Candida parapsilosis scavenges and regulates sulphur metabolism in an unusual way.
Candida parapsilosis can cause severe infections, particularly in people with weakened immune systems. The yeast has been identified as the culprit in several recent outbreaks of infection.
Like other microbes, C. parapsilosis searches its environment for nutrients. This might be in the soil or in the human body during infection. The mechanisms it uses to acquire nitrogen and carbon have been studied but nothing was known about its sulphur metabolism until now.
The team led by Professor Geraldine Butler from UCD School of Biomolecular & Biomedical Science and UCD Conway Institute have generated the largest collection to date of C. parapsilosis strains in which the function of more than 350 genes was disrupted.
Describing the research study, postdoctoral researcher, Dr Lisa Lombardi explained,
“We analysed how these strains would grow in more than 50 different conditions such as in the presence of drugs, or in the absence of specific amino acids. We coupled this information with other experiments to identify the individual contribution of different regulators of sulphur metabolism.”
Explaining the study findings that were recently published in the scientific journal, Nature Communications, Professor Geraldine Butler said,
“We found that C. parapsilosis evolved different ways to regulate how it acquires sulphur – both inorganic and organic types. By using these regulators, the yeast can survive in many places, from the human body to the environment, making it a more versatile pathogen.”
Some essential components of sulphur metabolism are not present in humans. This makes them very interesting to us as potential drug targets that are both effective (interfering with them would likely be harmful for the yeast) and specific (harmless for the infected patient).
Over the past 10 years, there has been a large increase in the number of outbreaks worldwide caused by strains of C. parapsilosis that are resistant to drug treatment. In 2023, the World Health Organisation rated this yeast as a high priority to target. The Butler group will now share the largest collection of C. parapsilosis gene disruptions with the scientific community to enable rapid progress in characterising this important pathogen.
“Our collection of gene disruptions will enable many future studies of virulence and drug resistance in this species. By investigating branches of its metabolism that are still not well characterised (such as sulphur metabolism), we can devise new strategies to control its spread”, said Dr Lombardi.
The team will now focus on establishing how sulphur metabolism contributes to infection in the human host and evaluating whether it can be a target for drug development, or for strategies aimed at containing the spread of the pathogen in the hospital environment.