Sterol biosynthesis and sterol uptake in the funal pathogen Pneumocsytis carinii

Grant, Tiffany

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Date Uploaded: 04/14/2016
Date Modified: 04/14/2016

Members of the fungal genus Pneumocystis colonize healthy mammalian hosts
without causing apparent disease, but colonization in immunocompromised hosts
may result in a potentially fatal pneumonia known as Pneumocystis pneumonia.
Although Pneumocystis are fungi, this genus has characteristics that make it atypical
among other fungi. Pneumocystis do not appear to synthesize the major fungal sterol,
ergosterol, and biochemical analyses have shown that they utilize cholesterol rather
than ergosterol as the bulk sterol. Pneumocystis carinii appears to scavenge exogenous sterols, including cholesterol, from its mammalian host. As a result, it has long been held that their ability to scavenge cholesterol from their hosts, and their inability to undergo sterol biosynthesis, makes them resistant to antifungal drugs that target ergosterol or ergosterol biosynthesis. However, genome scans and in vitro assays indicate the presence of sterol biosynthetic genes within the P. carinii genome, and targeted inhibition of these enzymes resulted in reduced viability of P. carinii,
suggesting that these enzymes are functional within the organism. Heterologous
expression of P. carinii sterol genes, along with biochemical analyses of the lipid
content of P. carinii cellular membranes, have provided an insight into sterol
biosynthesis and the sterol-scavenging mechanisms used by these fungi.

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