2024/12/16 by Elise Iracane, Alessia Buscaino · 1 voice
Medicine · Agricultural and Biological Sciences · #Fungal Infections and Studies #Plant Disease Resistance and Genetics #Phytoplasmas and Hemiptera pathogens
paper · pdf · doi:10.1073/pnas.2422896121
openalex created_date 2024/12/16 · openalex publication_date 2024/12/16 · openalex updated_date 2026/07/30
Microbial organisms face relentless environmental pressures that demand rapid adaptation for survival ( 1 , 2 ).This is especially true for pathogenic fungi that must adapt to extreme shifts when transitioning from natural niches to their human host, where they encounter immune defenses and antifungal drugs ( 3 ).In PNAS, Huang et al. investigate the evolutionary pathways leading to adaptation in the human fungal pathogen Cryptococcus ( 4 ).Cryptococcus neoformans and Cryptococcus deneoformans are closely related environmental fungi that can infect humans, causing life-threatening infections in immunocompromised individuals.Treatment options for Cryptococcus infections are limited, and resistance to existing antifungal therapies is common, posing serious challenges for clinical management ( 5 ).During infection, Cryptococcu s species must adapt to dramatic environmental changes as they transition from their natural reservoirs in soil and avian habitats to the human host ( 6 ).In challenging environments, hypermutator strains-microorganisms with elevated mutation rates-can provide short-term adaptive advantages, despite potential long-term fitness costs ( 7 ).The increased genetic variation generated by hypermutation enhances survival under fluctuating conditions and facilitates the acquisition of beneficial traits, including drug resistance ( 8 ).Central to this adaptability are transposable elements (TEs), mobile genetic elements that can produce mutations.However, uncontrolled TE activity can disrupt essential genes, imposing significant fitness costs.RNA interference (RNAi) plays a crucial role in suppressing TE mobilization in many organisms by degrading transposon-derived transcripts or seeding repressive chromatin structures ( 9 ).Accordingly, a previous study showed that two C. neoformans isolates lacking RNAi exhibit hypermutator phenotypes, characterized by elevated mutation rates due to amplification of the retrotransposon Cnl1 (C.neoformans LINE-1-like element).While these retrotransposons predominantly accumulate in subtelomeric regions, their integration into certain genes, such as FRR1 , confers drug resistance ( 10 ).Huang et al. investigate how the loss of RNAi and subsequent accumulation of TEs drive hypermutation and emergence of drug resistance in Cryptococcus species ( 4 ).Through screening of 387 C. neoformans isolates, the authors identified five additional RNAi-deficient strains, revealing that RNAi loss