Antifungal resistance mechanisms in dermatophytes.
Although fungi do not cause outbreaks or pandemics, the incidence of severe systemic fungal infections has increased significantly, mainly because of the explosive growth in the number of patients with compromised immune system. Thus, drug resistance in pathogenic fungi, including dermatophytes, is gaining importance. The molecular aspects involved in the resistance of dermatophytes to marketed antifungals and other cytotoxic drugs, such as modifications of target enzymes, over-expression of genes encoding ATP-binding cassette (ABC) transporters and stress-response-related proteins are reviewed. Emphasis is placed on the mechanisms used by dermatophytes to overcome the inhibitory action of terbinafine and survival in the host environment. The relevance of identifying new molecular targets, of expanding the understanding about the molecular mechanisms of resistance and of using this information to design new drugs or to modify those that have become ineffective is also discussed.
Martinez-Rossi
Nilce M
NM
Departamento de Genética, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, 14049-900 Ribeirao Preto, SP, Brazil. nmmrossi@usp.br
Peres
Nalu T A
NT
Rossi
Antonio
A
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D003883:Arthrodermataceae / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D025141:Drug Resistance, Fungal / Q000235:genetics; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009281:Naphthalenes / Q000494:pharmacology; D050603:Squalene Monooxygenase / Q000737:chemistry / Q000235:genetics; D000077291:Terbinafine
D000935:Antifungal Agents; D005656:Fungal Proteins; D009281:Naphthalenes; D050603:Squalene Monooxygenase; D000077291:Terbinafine