Thermotolerance is critical for fungal survival in vivo, yet how metabolic remodeling enables pathogenic fungi such as Cryptococcus neoformans to withstand heat stress remains unclear. Here, we identify the protein deacetylase Dac6 as a thermotolerance regulator in C. neoformans functioning independently of the yeast deacetylase Rpd3 and mirroring the heat-resistant phenotype of clinical isolates. Integrated multi-omics analyses reveal that Dac6 remodels histone acetylation and gene expression to reprogram amino acid metabolism under heat stress, thereby enhancing lysine and threonine utilization. Lysine and threonine are also among the most markedly altered metabolites in the host during cryptococcal infection, and Dac6 deletion impairs fungal utilization of these amino acids under heat stress in vitro and in vivo. Consequently, Dac6 deficiency leads to reduced lung and brain colonization and attenuated virulence in mice. Thus, Dac6 couples nutrient utilization to thermal adaptation, revealing a chromatin-guided metabolic strategy that supports fungal survival in the host.
In microbial communities, the taxa responsible for producing specific metabolites are often unknown, even when those metabolites accumulate consistently, and the community members that support or compete with this process remain poorly understood. This study aimed to identify taxa associated with succinate accumulation in mixed culture fermentation by correlating succinate concentrations with full-length rRNA operon amplicon profiles of microbial communities from bioreactors fed the organic fraction of municipal solid waste. The four OTUs associated with succinate were affiliated with Clostridium butyricum, Lactiplantibacillus plantarum, Leuconostoc gelidum, and Dysosmobacter welbionis. All tested strains produced succinate in axenic cultures, suggesting the corresponding taxa plausibly contributed to the original community, although their activity in mixed culture and its modulation by community interactions remain to be determined. L. plantarum demonstrated the highest succinate-producing capacity, reaching 1.27 ± 0.01 mM in modified MRS medium, supplemented with NaHCO3 (2 g/L). L. gelidum and D. welbionis produced up to 0.90 ± 0.00 and 0.82 ± 0.06 mM of succinate in MRS medium, followed by C. butyricum at 0.16 ± 0.02 mM in mineral medium supplemented with organic waste fraction. This approach enabled the identification of taxa not previously associated with succinate production, and provides a route to prioritise candidate producers in undefined mixed cultures for isolation, co-culture and synthetic community studies.
