Unlocking fungal defenses: How genome sequencing unveils the secrets of cycloheximide resistance.

Wingfield, B. D.*

Department of Biochemistry, Genetics and Biochemistry, Forestry and Agricultural Biotechnology Institute, University of Pretoria, South Africa

The advent of fungal genome sequencing has revolutionized the understanding of molecular mechanisms underlying drug resistance, including cycloheximide resistance in certain fungi such as yeasts and Ophiostomatales. Cycloheximide, a well-known inhibitor of eukaryotic protein synthesis, targets the ribosome's peptidyl transferase centre. However, some fungi exhibit resistance, which has puzzled researchers for decades. Genomic analyses have provided unprecedented insights into the genetic mutations responsible for this resistance, particularly alterations in ribosomal proteins or components of the translation machinery. In yeasts, specific mutations in the ribosomal protein large subunit genes have been identified as the primary cause of cycloheximide resistance. Similarly, genome sequencing of Ophiostomatales has revealed analogous mutations, which confer resistance by modifying the drug-binding site. Access to complete genome sequences has enabled the identification of these genetic variations with high precision, offering new avenues for studying fungal resistance to cycloheximide.

Keywords: fungi, cycloheximide, resistance, ribosome, genome