title: Identification of relevant single-nucleotide polymorphisms in Pneumocystis jirovecii: relationship with clinical data.
abstract: Pneumocystis jirovecii 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. jirovecii 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, SOD110, SOD215, and DHFR312) and specific clinical parameters: mt85C was associated with undiagnosed or atypical PcP episodes and favourable follow-up; SOD215C was associated with favourable follow-up; and DHFR312T was associated with PcP cases presenting moderate to high parasite burdens. The genotypes mt85C/SOD215C and SOD110T/SOD215C were found to be associated with less virulent P. jirovecii infections, whereas the genotype SOD110T/SOD215T 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.
authors.affiliation: Unidade de Protozoários Oportunistas/VIH e Outras Protozooses/CMDT, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisboa, Portugal.
authors.forename: F
authors.initials: F
authors.lastname: Esteves
authors.forename: J
authors.initials: J
authors.lastname: Gaspar
authors.forename: T
authors.initials: T
authors.lastname: Marques
authors.forename: R
authors.initials: R
authors.lastname: Leite
authors.forename: F
authors.initials: F
authors.lastname: Antunes
authors.forename: K
authors.initials: K
authors.lastname: Mansinho
authors.forename: O
authors.initials: O
authors.lastname: Matos
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000382:microbiology*; D000328:Adult; D000368:Aged; D001483:Base Sequence; D045303:Cytochromes b / Q000235:genetics; D004271:DNA, Fungal / Q000032:analysis / Q000235:genetics*; D004094:Dihydropteroate Synthase / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D016533:Mycological Typing Techniques; D045363:Pneumocystis carinii / Q000235:genetics* / Q000302:isolation & purification; D011020:Pneumonia, Pneumocystis / Q000382:microbiology*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011174:Portugal; D012313:RNA / Q000235:genetics; D000077278:RNA, Mitochondrial; D017422:Sequence Analysis, DNA; D013482:Superoxide Dismutase / Q000235:genetics; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D055815:Young Adult
chemical_list: D004271:DNA, Fungal; D000077278:RNA, Mitochondrial; D012313:RNA; D045303:Cytochromes b; D013482:Superoxide Dismutase; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase