Excreted chemicals form a major component of the language through which living cells communicate with each other. When these chemicals are gaseous, they can mediate rapid interactions between seemingly unconnected cell populations. Gaseous mediators are widespread in biology. For instance, plants use an elaborate vocabulary of volatile compounds to attract pollinators or warn conspecifics of predators. Some gases such as hydrogen sulfide are produced by most cell types and can impact tissue in diverse ways: while high doses of sulfide can be toxic, in controlled doses, the gas can regulate blood vessel diameter, enhance biofilm formation in the gut microbiome, and affect longevity in a range of organisms such as yeast, flies and rodents. Interestingly, many other volatile sulfur compounds are produced in microbial cells, but their functions are not well understood. Better knowledge of the metabolic pathways that produce and consume volatile compounds thus holds potential for novel therapeutics.
The overall aim of this project was to identify a hidden pathway in the budding yeast, Saccharomyces cerevisiae, which can assimilate sulfide into organic sulfur compounds—essential nutrients for all cell types. Our preliminary work had revealed gaps in the current understanding of yeast sulfur metabolism; even when a key gene involved in sulfide assimilation (MET17) was deleted, yeast could assimilate sulfide through an unknown alternative mechanism, however only in cultures exceeding a threshold cell density. Thus, to understand how these yeast populations overcome their metabolic defect in a density-dependent manner, we aimed to 1) develop quantitative tools to understand their sulfide-response, 2) identify gene(s) in the alternative sulfide metabolism, and 3) reveal the function of these genes when the primary route of sulfide assimilation was not perturbed.
Synergistically combining mathematical modelling and quantitative experiments, we elucidated the mechanism by which MET17-lacking yeast overcome their metabolic defect. We found that the uncharacterized locus YLL058W carries out sulfide assimilation in the absence of MET17, albeit at a low efficiency, making the growth outcome sensitive to factors that affect sulfide accumulation: cell density and gas escape. Thus, our research resolved misconceptions and revealed novel aspects of sulfur metabolism in budding yeast. Furthermore, we developed generalisable quantitative tools for studying diverse chemical-mediated interactions in microbial communities.
