Functional Characterization of the Pneumocystis jirovecii Potential Drug Targets dhfs and abz2 Involved in Folate Biosynthesis

摘要: Pneumocystis species are fungal parasites colonizing mammal lungs with strict host specificity. jirovecii is the human-specific and can turn into an opportunistic pathogen causing severe pneumonia in immunocompromised individuals. This disease currently second most frequent life-threatening invasive infection worldwide. The efficient drug, cotrimoxazole, presents serious side effects, resistance to this drug emerging. search for new targets development of drugs thus utmost importance. recent release P. genome sequence opens a era task. It now be carried out on actual inhibited instead those relatively distant model carinii, infecting rats. We focused folic acid biosynthesis pathway because (i) it widely used therapeutic intervention, (ii) involves several enzymes that essential have no human counterparts. In study, we report identification two such potential within jirovecii, dihydrofolate synthase (dhfs) aminodeoxychorismate lyase (abz2). function these was demonstrated by rescue null allele orthologous gene Saccharomyces cerevisiae.