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Clinical Significance and Phylogenetic Relationship of Novel Australian Pneumocystis jirovecii Genotypes
Author(s) -
Sebastiaan J. van Hal,
Fèlix Gilgado,
Tom Doyle,
Joel Barratt,
Damien Stark,
Wieland Meyer,
John Harkness
Publication year - 2009
Publication title -
journal of clinical microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.349
H-Index - 255
eISSN - 1070-633X
pISSN - 0095-1137
DOI - 10.1128/jcm.02102-08
Subject(s) - dhps , dihydropteroate synthase , haplotype , biology , pneumocystis jirovecii , genotype , genetics , internal transcribed spacer , ribosomal rna , typing , phylogenetic tree , microbiology and biotechnology , virology , gene , immunology , plasmodium falciparum , pyrimethamine , human immunodeficiency virus (hiv) , malaria
Pneumocystis jirovecii is an important opportunistic pathogen in immunocompromised patients. Molecular typing is employed to study this pathogen, as no culture system exists. No AustralianP. jirovecii strains have been previously studied. Direct sequencing, targeting the internal transcribed spacer (ITS) regions of the nuclear rRNA operon, the mitochondrial large-subunit rRNA (mt LSU rRNA), and the dihydropteroate synthase (DHPS) gene, was performed on 68 Australian samples, collected between 2001 and 2007. Seven novel Australian ITS haplotypes (a composite of the ITS1 and ITS2 regions) were identified (SYD1m, SYD1g, Isyd2, Esyd3, Osyd4, Ag, and Hc). A dendrogram of published ITS haplotypes revealed that of the seven novel haplotypes, three (SYD1m, SYD1g, and Osyd4) are closely related to the haplotype Eg. Applying statistical parsimony, an Australian haplotype network was constructed which identified Eg as the ancestral haplotype, with two unresolved loops encountered. This suggests that the ITS lacks the resolution required for evolutionary analysis. Only two mt LSU rRNA genotypes were detected, with genotype 1 predominating. Mutant DHPS genotypes were present in 13% (8/60) of the samples. The novel haplotype Isyd2 was associated with less severe disease than the other Australian haplotypes. In contrast, patients with mutant DHPS genotypes were more likely to have severe disease, require invasive ventilation, and have a poor outcome than patients with wild-type DHPS genotypes. In conclusion, genetic clinical correlates continue to be found forPneumocystis pneumonia; however, they remain controversial and warrant further study.

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