The basidiomycete causes life-threatening infections in immunocompromised patients, and available chemotherapeutic agents are potentially toxic or have limited efficacy. is very sensitive to selected benzimidazole compounds (e.g. albendazole), which act by disrupting microtubules through binding to the β-tubulin subunit. To understand the basis for this benzimidazole sensitivity, we have characterized β-tubulin genes and their expression. Analysis of PCR amplification products, genomic and cDNA clones and Southern blots identified two β-tubulin genes. contains seven introns, including one that splits the start codon, and encodes a 447 amino acid protein with >80% identity to most other β-tubulins. A partial sequence of revealed a higher density of introns and a considerably more divergent β-tubulin. The relative expression of to determined by reverse-transcription PCR was about 3:1, consistent with a more limited role for the product. Comparisons of β-tubulin sequences from and from various benzimidazole-sensitive and -resistant organisms strongly suggest that the product represents the primary benzimidazole target. This was supported by the identification of a His6 to Gin change in from three independently isolated albendazole-resistant mutants.


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