Genetic Divergence of the Dihydrofolate Reductase and Dihydropteroate Synthase Genes in Pneumocystis carinii from 7 Different Host Species

To investigate the phylogenetic and therapeutic implications of the genetic divergence in the dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) genes among different Pneumocystis carinii strains, these 2 genes in P. carinii obtained from 7 different host species were sequenced. Pair...

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Bibliographic Details
Published in:The Journal of infectious diseases 2001-11, Vol.184 (10), p.1358-1362
Main Authors: Ma, Liang, Imamichi, Hiromi, Sukura, Antti, Kovacs, Joseph A.
Format: Article
Language:English
Subjects:
Amino acids
Animals
Aotidae
Biological and medical sciences
Concise Communications
DHFR gene
DHPS gene
Dihydropteroate Synthase - genetics
Dogs
Enzymes
Evolutionary genetics
Ferrets
Fundamental and applied biological sciences. Psychology
Fungi
Genetic mutation
Growth, nutrition, metabolism, transports, enzymes. Molecular biology
Human mycoses
Humans
Infectious diseases
Medical sciences
Mice
Microbiology
Molecular Sequence Data
Mycology
Mycoses
Mycoses of the respiratory system
Phylogenetics
Pneumocystis - classification
Pneumocystis - enzymology
Pneumocystis - genetics
Pneumocystis carinii
Pneumocystis Infections - microbiology
Rabbits
Rats
Species Specificity
Tetrahydrofolate Dehydrogenase - genetics
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Summary:To investigate the phylogenetic and therapeutic implications of the genetic divergence in the dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) genes among different Pneumocystis carinii strains, these 2 genes in P. carinii obtained from 7 different host species were sequenced. Pairwise comparison of the DHPS sequences demonstrated 6%–24% and 6%–30% divergence in the nucleotide and deduced amino acid sequences, respectively. The DHFR gene was even more divergent, with differences of 15%–34% and 18%–42% in the nucleotide and deduced amino acid sequences, respectively. Phylogenetic analysis of DHFR and DHPS sequences revealed that all P. carinii strains were confined within a distinct group that was closely related to ascomycete fungi and that human-derived P. carinii was most closely related to monkey-derived P. carinii. Recognizing the substantial differences in the DHFR and DHPS genes among P. carinii from different host species has important implications for drug discovery and the development of new diagnostic methods
ISSN:0022-1899
1537-6613
DOI:10.1086/324208