Penicillium marneffei is an intracellular dimorphic fungus that can cause a fatal disseminated disease in human immunodeficiency virus-infected patients. The factors that affect the pathogenicity of this fungus remain unclear. Here, we report the isolation and characterization of the gpdA
cDNA and genomic clones encoding
glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in P. marneffei. Phylogenetic analysis of GAPDH amino acid sequences demonstrated the evolutionary relationship of P. marneffei to other fungi, including the intracellular pathogen Ajellomyces capsulatus. To assess the central importance of phagocytic cells in defence against P. marneffei
infection, we used Northern blotting to investigate the response of the
isocitrate lyase-encoding gene (acuD) and gpdA to nutrient deprivation inside macrophages. The results revealed that after macrophage internalization, the gene involved in the
glyoxylate cycle, acuD, showed higher expression levels as early
as 2 h from the start of co-incubation, and the differential expression could be observed again at 8 h after
infection. In contrast, the expression of gpdA was downregulated in the yeast phase, as well as during macrophage
infection after 2, 4 and 8 h of
infection. The induction of P. marneffei acuD was shown to be coordinated with the downregulation of the glycolytic gpdA gene, implying that the cytoplasmic environment of macrophages is deficient in
glucose and the
glyoxylate pathway could be used by this pathogen to allow subsistence on two-
carbon compounds within the host cell following its intracellular persistence.