TY - JOUR
T1 - Distinct effect of calorie restriction between congenic mating types of Cryptococcus neoformans
AU - Oliveira, Natalia Kronbauer
AU - Yoo, Kyungyoon
AU - Bhattacharya, Somanon
AU - Gambhir, Rina
AU - Kirgizbaeva, Nigina
AU - García, Pilar Arcones
AU - Prados, Ignacio Pompa
AU - Fernandes, Caroline Mota
AU - Del Poeta, Maurizio
AU - Fries, Bettina C.
N1 - Publisher Copyright:
© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024.
PY - 2024/12
Y1 - 2024/12
N2 - Cryptococcus neoformans (Cn) is an opportunistic yeast that causes meningoencephalitis in immunocompromised individuals. Calorie restriction (CR) prolongs Cn replicative lifespan (RLS) and mimics low-glucose environments in which Cn resides during infection. The effects of CR-mediated stress can differ among strains and have only been studied in MATα cells. Cn replicates sexually, generating two mating types, MATα and MATa. MATα strains are more dominant in clinical and environmental isolates. We sought to compare the effects of CR stress and longevity regulation between congenic MATα and MATa. Although MATα and MATa cells extended their RLS in response to CR, they engaged different pathways. The sirtuins were upregulated in MATα cells under CR, but not in MATa cells. RLS extension was SIR2-dependent in KN99α, but not in KN99a. The TOR nutrient-sensing pathway was downregulated in MATa strains under CR, while MATα strains demonstrated no difference. Lower oxidative stress and higher ATP production were observed in KN99α cells, possibly due to higher SOD expression. SIR2 was important for mitochondrial morphology and function in both mating types. Increased ATP production during CR powered the upregulated ABC transporters, increasing efflux in MATα cells. This led to enhanced fluconazole tolerance, while MATa cells remained sensitive to fluconazole. Our investigation highlights differences in the response of the mating types to CR.
AB - Cryptococcus neoformans (Cn) is an opportunistic yeast that causes meningoencephalitis in immunocompromised individuals. Calorie restriction (CR) prolongs Cn replicative lifespan (RLS) and mimics low-glucose environments in which Cn resides during infection. The effects of CR-mediated stress can differ among strains and have only been studied in MATα cells. Cn replicates sexually, generating two mating types, MATα and MATa. MATα strains are more dominant in clinical and environmental isolates. We sought to compare the effects of CR stress and longevity regulation between congenic MATα and MATa. Although MATα and MATa cells extended their RLS in response to CR, they engaged different pathways. The sirtuins were upregulated in MATα cells under CR, but not in MATa cells. RLS extension was SIR2-dependent in KN99α, but not in KN99a. The TOR nutrient-sensing pathway was downregulated in MATa strains under CR, while MATα strains demonstrated no difference. Lower oxidative stress and higher ATP production were observed in KN99α cells, possibly due to higher SOD expression. SIR2 was important for mitochondrial morphology and function in both mating types. Increased ATP production during CR powered the upregulated ABC transporters, increasing efflux in MATα cells. This led to enhanced fluconazole tolerance, while MATa cells remained sensitive to fluconazole. Our investigation highlights differences in the response of the mating types to CR.
UR - https://www.scopus.com/pages/publications/85200486450
U2 - 10.1038/s41598-024-69087-y
DO - 10.1038/s41598-024-69087-y
M3 - Article
C2 - 39107496
AN - SCOPUS:85200486450
SN - 2045-2322
VL - 14
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 18187
ER -