title: Dihydropteroate synthase gene mutation rates in Pneumocystis jirovecii strains obtained from Iranian HIV-positive and non-HIV-positive patients.
abstract: The dihydropteroate sulfate (DHPS) gene is associated with resistance to sulfa/sulfone drugs in Pneumocystis jirovecii. We investigated the DHPS mutation rate in three groups of Iranian HIV-positive and HIV-negative patients by polymerase chain reaction-restricted fragment length polymorphism analysis. Furthermore, an association between P. jirovecii DHPS mutations and strain typing was investigated based on direct sequencing of internal transcribed spacer region 1 (ITS1) and ITS2. The overall P. jirovecii DHPS mutation rate was (5/34; 14.7%), the lowest rate identified was in HIV-positive patients (1/16; 6.25%) and the highest rate was in malignancies patients (3/11; 27.3%). A moderate rate of mutation was detected in chronic obstructive pulmonary disease (COPD) patients (1/7; 14.3%). Most of the isolates were wild type (29/34; 85.3%). Double mutations in DHPS were detected in patients with malignancies, whereas single mutations at codons 55 and 57 were identified in the HIV-positive and COPD patients, respectively. In this study, two new and rare haplotypes were identified with DHPS mutations. Additionally, a positive relationship between P. jirovecii strain genotypes and DHPS mutations was identified. In contrast, no DHPS mutations were detected in the predominant (Eg) haplotype. This should be regarded as a warning of an increasing incidence of drug-resistant P. jirovecii strains.
authors: Mycobacteriology Research Center, National Research Institute of Tuberculosis and Lung Disease (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran Tarbiat Modares University, Medical Faculty, Parasitology Department, Tehran, Iran m.sheikholslami@gmail.com.
authors: Maryam-Fatemeh
authors: MF
authors: Sheikholeslami
authors: Tarbiat Modares University, Medical Faculty, Parasitology Department, Tehran, Iran.
authors: Javid
authors: J
authors: Sadraei
authors: Mycobacteriology Research Center, National Research Institute of Tuberculosis and Lung Disease (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors: Parisa
authors: P
authors: Farnia
authors: Tarbiat Modares University, Medical Faculty, Biotechnology Department, Tehran, Iran.
authors: Mehdi
authors: M
authors: Forozandeh Moghadam
authors: Iranian HIV/AIDS Research Center, Imam Khomini Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors: Hamid
authors: H
authors: Emadikochak
mesh_terms: D004271:DNA, Fungal / Q000737:chemistry / Q000235:genetics; D021903:DNA, Ribosomal Spacer / Q000737:chemistry / Q000235:genetics; D004094:Dihydropteroate Synthase / Q000235:genetics*; D005838:Genotype; D015658:HIV Infections / Q000150:complications; D006239:Haplotypes; D006801:Humans; D007492:Iran; D058889:Molecular Typing; D059645:Mutation Rate; D016533:Mycological Typing Techniques; D016720:Pneumocystis Infections / Q000382:microbiology*; D045363:Pneumocystis carinii / Q000145:classification / Q000201:enzymology* / Q000235:genetics* / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D017422:Sequence Analysis, DNA
chemical_list: D004271:DNA, Fungal; D021903:DNA, Ribosomal Spacer; D004094:Dihydropteroate Synthase
keywords: Iranian immunocompromized patients; Pneumocystis jirovecii; dihydroptroate sulfate gene; internal transcribed region 1; internal transcribed region 2