Dihydropteroate synthase polymorphisms in Pneumocystis carinii.

Lane, B. R.; Ast, J. C.; Hossler, P. A.; Mindell, D. P.; Bartlett, M. S.; Smith, J. W.; Meshnick, S. R.

doi:10.1093/infdis/175.2.482

Cited by 176Pneumocystis jirovecii pneumonia detection and treatmentPneumonia and Respiratory InfectionsAntibiotic Resistance in Bacteria

Dihydropteroate synthase polymorphisms in Pneumocystis carinii.

Lane, B. R., Ast, J. C., Hossler, P. A., Mindell, D. P., Bartlett, M. S., Smith, J. W., Meshnick, S. R.·1997·Journal of Infectious Diseases

DOI 10.1093/infdis/175.2.482

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Abstract

Sulfa drugs are widely used in the treatment and prophylaxis of Pneumocystis carinii pneumonia. The nucleotide sequences of the sulfa target enzyme, dihydropteroate synthase (DHPS), differed substantially in human-, rat-, and mouse-derived P. carinii. Sequence variation also existed in the DHPSs from human-derived isolates. Six nucleotide changes were found in 6 human isolates; each was nonsynonymous and resulted in an amino acid change. Several of these changes were in highly conserved regions and are similar to those that cause sulfa resistance in other organisms. These data suggest that the human-derived P. carinii DHPS may be evolving under positive selective pressure from sulfa drugs.

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DHPS gene mutations have not been found in other mammalian Pneumocystis species that have not been exposed to sulfa medications.
“Furthermore, DHPS gene mutations have not been found in other mammalian Pneumocystis species that have not been exposed to sulfa medications (18,27).”
From Dihydropteroate Synthase Gene Mutations inPneumocystisand Sulfa Resistance (2004) · cites this paper as [18]
The Results (page not specified) report DHPS sequence changes in rodent-derived Pneumocystis: 17 of 45 nucleotide changes resulted in 16 amino-acid changes. The paper finds a higher proportion of amino-acid-changing substitutions in human-derived isolates, but it does not say that DHPS mutations are absent from other mammalian hosts. (LLM, conf=0.84)
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The region of the DHPS gene in which mutations have been identified is highly conserved among other organisms, including Plasmodium falciparum, Streptococcus pneumoniae, E. coli, and Bacillus subtilis.
“The region of the DHPS gene in which mutations have been identified is one that is highly conserved among other organisms, including Plasmodium falciparum, Streptococcus pneumoniae, E. coli, and Bacillus subtilis (18).”
From Dihydropteroate Synthase Gene Mutations inPneumocystisand Sulfa Resistance (2004) · cites this paper as [18]
Sulfa medications appear to exert selective pressure on Pneumocystis, as the DHPS gene is more likely to display mutations in highly conserved regions in patients with PCP who have previously been exposed to sulfa medications.
“Sulfa medications appear to exert selective pressure on Pneumocystis (18), as the DHPS gene is more likely to display mutations in highly conserved regions in patients with PCP who have previously been exposed to sulfa medications (19–25).”
From Dihydropteroate Synthase Gene Mutations inPneumocystisand Sulfa Resistance (2004) · cites this paper as [18]
Other mutations near this site also cause sulfa resistance in S. pneumoniae and P. falciparum.
“Other mutations near this site also cause sulfa resistance in S. pneumoniae and P. falciparum (18).”
From Dihydropteroate Synthase Gene Mutations inPneumocystisand Sulfa Resistance (2004) · cites this paper as [18]

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Authors: Lane, B. R., Ast, J. C., Hossler, P. A., Mindell, D. P., Bartlett, M. S., Smith, J. W., & Meshnick, S. R.
Affiliations: University of Michigan (US)
Corresponding author: Meshnick, S. R.
ORCID: Lane, B. R.
Ast, J. C.
Mindell, D. P.
Venue: Journal of Infectious Diseases
Publisher: Oxford University Press (OUP)
Published: 1997-02-01
Volume: 175
Issue: 2
Pages: 482-485
ISSN: 0022-1899 (ISSN-L)
1537-6613
DOI: 10.1093/infdis/175.2.482
OpenAlex: W1999275308
Cited by: 176
References: 14
Citations by year: 2026: 1 · 2024: 1 · 2023: 4 · 2022: 3 · 2021: 5 · 2019: 4 · 2018: 4 · 2017: 4 · 2016: 3 · 2015: 7 · 2014: 6 · 2013: 4 · 2012: 5
FWCI: 9.99
Type: journal article
Language: en
Open access: closed
Locations: The Journal of Infectious Diseases (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01ai031775-05)
National Institute of Allergy and Infectious Diseases (AI-31775, AI-72647)
Topics: Health Sciences › Medicine › Epidemiology › Pneumocystis jirovecii pneumonia detection and treatment
Health Sciences › Medicine › Epidemiology › Pneumonia and Respiratory Infections
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
Keywords: Pneumocystis carinii, dihydropteroate synthase, sulfonamides, Pneumocystis carinii pneumonia, nucleotide variation, non-synonymous mutations, positive selection
MeSH terms: Amino Acid Sequence, Animals, Dihydropteroate Synthase, DNA, Fungal, Humans, Molecular Sequence Data, Pneumocystis, Polymorphism, Genetic, Genetic Variation, Polymerase Chain Reaction, Sequence Alignment, Pneumocystis Infections, Sequence Homology, Amino Acid, Sequence Analysis, DNA, Mice, Rats

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Dihydropteroate synthase polymorphisms in Pneumocystis carinii.

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