Clinical epidemiology of pulmonary aspergillosis in hospitalized patients and contribution of Cyp51A, Yap1, and Cdr1B mutations to voriconazole resistance in etiologic Aspergillus species

AbstractPulmonary aspergillosis is a life-threatening fungal infection with worldwide distribution. In the present study, clinical epidemiology of pulmonary aspergillosis and antifungal susceptibility of etiologicAspergillus species were evaluated in one-hundred fifty patients with special focus on the frequency of voriconazole resistance. All the cases were confirmed by the clinical pictures, laboratory findings, and isolation of etiologicAspergillus species which belonged to two major species, i.e.,A. flavus andA. fumigatus. Seventeen isolates displayed voriconazole MIC greater than or equal to the epidemiological cutoff value. Expression ofcyp51A,Cdr1B, andYap1 genes was analyzed in voriconazole-intermediate/resistant isolates. InA. flavus, Cyp51A protein sequencing showed the substitutions T335A and D282E. In theYap1 gene, A78C replacement led to Q26H amino acid substitution that was not reported previously inA. flavus resistant to voriconazole. No mutations associated with voriconazole resistance were found in the three genes ofA. fumigatus. The expression ofYap1 was higher than that of two other genes in bothA. flavus andA. fumigatus. Overall, voriconazole-resistant strains of  both A. fumigatus  and A. flavus demonstrated overexpression ofCdr1B,Cyp51A, andYap1 genes  compared to voriconazole-susceptible strains. Although there are still ambiguous points about the mechanisms of azole resistance, our results showed that mutations were not present in majority of res...
Source: European Journal of Clinical Microbiology and Infectious Diseases - Category: Microbiology Source Type: research