Suppressed Protein Translation Caused by MSP-8 Deficiency Determines Fungal Multidrug Resistance with Fitness Cost.

ABSTRACT: Antifungal resistance, particularly the rise of multidrug-resistance strains, poses a significant public health threat. In this study, the study identifies a novel multidrug-resistance gene, msp-8, encoding a helicase, through experimental evolution with Neurospora crassa as a model. Deletion of msp-8 conferred multidrug resistance in N. crassa, Aspergillus fumigatus, and Fusarium verticillioides. However, the transcript levels of genes encoding known drug targets or efflux pumps remain unaltered with msp-8 deletion. Interestingly, MSP-8 interacted with ribosomal proteins, and this mutant displays compromised ribosomal function, causing translational disturbance. Notably, inhibition of protein translation enhances resistance to azoles, amphotericin B, and polyoxin B. Furthermore, MSP-8 def

SUBMITTER: Zhou M 

PROVIDER: S-EPMC11809369 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature