The gene polymorphisms of drug targets in Pneumocystis jiroveci isolates

Abstract

Objective To investigate gene polymorphisms of drug targets and mutations associated with drug resistance in Pneumocystis jiroveci (P. jiroveci) isolates. Methods Among 148 samples isolated from human immunodeficiency virus(HIV)infected patients with pneumonia in Guangdong, mitochondrid larg subunit rRNA (mtLSUrRNA) gene was amplified from 51 samples. Dihydropteroate synthase (DHPS), dihydrofolate reductase (DHFR) and Cytochrome b (CYB) genes of P. jiroveci were detected by gene sequencing, and compared with the reference sequences in GenBank to evaluate gene polymorphisms. Results P. jirovecii DHPS, DHFR and CYB genes were all successfully amplified from 51 samples. For DHPS gene, 48 (94.1%) were wild-type and 3 (5.9%) had gene mutation associated with drug resistance. For DHFR gene, 30 were wild-type, and 21 had a synonymous mutation at position 312, and 1 nonsynonymous mutation at position 188. There were no mutations associated with drug resistance. For CYB gene, polymorphisms of were detected at 5 sites, 4 of which were synonymous mutations, 1 was non-synonymous mutation. No mutation associated with drug resistance was found. Based on the gene polymorphism of CYB6, the strains can be classified into 6 genotypes, and 2 were first detected, including 25 CYB1, 13 CYB2, 2 CYB5, 4 CYB8, as well as newly detected 4 CYB10 and 3 CYB11 strains. Conclusions The mutations associated with drug resistance in P. jiroveci isolates in Guangdong remain uncommon. CYB gene shows gene polymorphisms and can be selected as one of targeted genes for multilocus sequence typing. Key words: Pneumocystis jirovecii; Polymorphism, genetic; Drug targets; Gene mutation