Abstract
Penicillium marneffei (synonym: Talaromyces marneffei) is the most important pathogenic thermally dimorphic fungus in China and Southeastern Asia. The HIV/AIDS pandemic, particularly in China and other Southeast Asian countries, has led to the emergence of P. marneffei infection as an important AIDS-defining condition. Recently, we published the genome sequence of P. marneffei. In the P. marneffei genome, 23 polyketide synthase genes and two polyketide synthase-non-ribosomal peptide synthase hybrid genes were identified. This number is much higher than those of Coccidioides immitis and Histoplasma capsulatum, important pathogenic thermally dimorphic fungi in the Western world. Phylogenetically, these polyketide synthase genes were distributed evenly with their counterparts found in Aspergillus species and other fungi, suggesting that polyketide synthases in P. marneffei did not diverge from lineage-specific gene duplication through a recent expansion. Gene knockdown experiments and ultra-high performance liquid chromatography-photodiode array detector/electrospray ionization-quadruple time of flight-mass spectrometry analysis confirmed that at least four of the polyketide synthase genes were involved in the biosynthesis of various pigments in P. marneffei, including melanin, mitorubrinic acid, mitorubrinol, monascorubrin, rubropunctatin, citrinin and ankaflavin, some of which were mycotoxins and virulence factors of the fungus.
Highlights
Penicillium marneffei is one of several known thermally dimorphic fungi and an important pathogen endemic in tropical Southeast Asian countries.P. marneffei causes respiratory, cutaneous and subcutaneous, systemic, and even disseminated mycoses in humans [1,2,3,4]
Hong Kong, situated in the tropical Southeast Asian area, is affected by P. marneffei infections and approximately 8% of patients with HIV/AIDS in this city are infected with this pathogenic fungus [6]
It was found that the genome of P. marneffei contains a total of 25 putative pks genes [18], which is much higher in number than in other thermally dimorphic fungi, where there are only one pks gene for Histoplasma capsulatum and ten for Coccidioides immitis [19]
Summary
Penicillium marneffei (synonym: Talaromyces marneffei) is one of several known thermally dimorphic fungi and an important pathogen endemic in tropical Southeast Asian countries. It was found that the genome of P. marneffei contains a total of 25 putative pks genes [18], which is much higher in number than in other thermally dimorphic fungi, where there are only one pks gene for Histoplasma capsulatum and ten for Coccidioides immitis [19]. These 18 groups of putative pks genes could potentially produce 18 different polyketide metabolites Twelve of these 21 gene candidates belong to the non-reducing type, whereas the remaining nine belong to the reducing type, which, on top of the KS, AT and ACP domains, contain the dehydrogenase (DH) and ketoreductase (KR) domains [18] (Figure 1). The nine reducing PKSs of P. marneffei are clustered with the reducing PKSs of other fungi in the tree with high bootstrap support (Figure 1). Studies over the past few years have revealed that some of the compounds which constitute these pigments represent known virulence factors for other fungi or novel virulence factors [18,21,23,24,25], whereas others represent pigments that have been used in various industries for over a thousand years [20,26,27,28]
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