Identification of relevant single-nucleotide polymorphisms in Pneumocystis jirovecii: relationship with clinical data

摘要

Pneumocystis jirovedi is a poorly understood pathogen that causes opportunistic pneumonia (Pneumocystis pneumonia (PcP)) in patients with AIDS. The present study was aimed at correlating genetic differences in P. jirovedi isolates and clinical patient data. A description of genetic diversity in P. jirovecii isolates from human immunodeficiency virus-positive patients, based on the identification of multiple single-nucleotide polymorphisms (SNPs) at five distinct loci encoding mitochondrial large-subunit rRNA (mtLSU rRNA), cytochrome b (CYB), superoxide dismutase (SOD), dihydrofolate reductase (DHFR), and dihydropteroate synthase (DHPS), was achieved using PCR with DNA sequencing and restriction fragment length polymorphism analysis. The statistical analysis revealed several interesting correlations among the four most relevant SNPs (mt85, SOD 110, SOD2I5, and DHFR3I2) and specific clinical parameters: mtS5C was associated with undiagnosed or atypical PcP episodes and favourable follow-up; SOD2I5C was associated with favourable follow-up; and DHFR3I2T was associated with PcP cases presenting moderate to high parasite burdens. The genotypes mt85CISOD2l5C and SOD/ I0TI SOD2I5C were found to be associated with less virulent P. jirovedi infections, whereas the genotype SOD/ I0TISOD2I5T was found to be related to more virulent PcP episodes. The present work demonstrated that potential P. jirovecii haplotypes may be related to the clinical data and outcome of PcP.