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Pteroylpolyglutamate synthesis by lung- and culture-derived Pneumocystis carinii
Y L Hong1, M S Bartlett, S Queener
1Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor 48109-2029, USA.
Abstract:
Pneumocystis carinii synthesizes folates de novo from exogenous p-aminobenzoic acid (pABA). Lung-derived organisms take up [3H]pABA in vitro except in the presence of sulfamethoxazole. Supernatants from spinner-flask cultures take up [3H]pABA if they were inoculated with lungs from infected rats, but not if they were inoculated with lungs from uninfected rats. P. carinii folates consist primarily of pteroylpentaglutamates. Plasmodium falciparum, in contrast, contains primarily pteroyltetraglutamates. Culture-derived organisms synthesize folates at a four-fold higher specific activity than lung-derived organisms, possibly because they contain less contaminating lung debris. These data suggest that P. carinii remains metabolically active in culture for at least 4 days.
Insights
Pneumocystis carinii synthesizes essential folates from p-aminobenzoic acid (pABA). This study confirms P. carinii
Area of Science:
- Microbiology
- Parasitology
- Biochemistry
Background:
- Pneumocystis carinii is an opportunistic pathogen that causes pneumonia in immunocompromised individuals.
- Folate synthesis is crucial for microbial survival and proliferation.
- Understanding the metabolic pathways of P. carinii is vital for developing targeted therapies.
Purpose of the Study:
- To investigate the de novo folate synthesis pathway in Pneumocystis carinii.
- To assess the metabolic activity of P. carinii in culture.
- To characterize the folate forms synthesized by P. carinii.
Main Methods:
- In vitro uptake of radiolabeled p-aminobenzoic acid ([3H]pABA) by lung-derived P. carinii.
- Assessment of [3H]pABA uptake in the presence of sulfamethoxazole.
- Analysis of folate composition in P. carinii using culture and lung-derived organisms.
- Comparison of folate synthesis specific activity between culture- and lung-derived P. carinii.
Main Results:
- P. carinii utilizes exogenous p-aminobenzoic acid (pABA) for de novo folate synthesis.
- Sulfamethoxazole inhibits the uptake of pABA by P. carinii.
- P. carinii folates are primarily pteroylpentaglutamates, distinct from Plasmodium falciparum's pteroyltetraglutamates.
- Culture-derived P. carinii exhibits higher folate synthesis specific activity than lung-derived organisms.
Conclusions:
- P. carinii possesses a functional de novo folate synthesis pathway.
- The organism's metabolic activity is sustained in culture for at least 4 days.
- These findings provide insights into P. carinii's metabolic requirements and potential therapeutic targets.