Penicillium marneffei is an important fungal pathogen of humans, in particular those who are immunocompromised. P. marneffei has the capacity to alternate between a hyphal and a yeast growth form, a process known as dimorphic switching, in response to temperature. P. marneffei grows in the hyphal form at 25°C and in the yeast form at 37°C. The hyphal form produces conidia which are likely to be the infectious agent while the yeast growth form is the pathogenic form found in infected patients. These yeast cells exist intracellularly in the mononuclear phagocyte system of the host. The molecular events which establish and maintain the developmental states and control of the dimorphic switching process in P. marneffei are poorly understood.
P. marneffei is the only true pathogen in a genus comprising a large number of species and is also the only dimorphic fungus in this group. As an intracellular pathogen, P. marneffei must be able to utilise the available nutrient sources in order to grow while evading or tolerating the host’s defence systems. The genes required for tyrosine catabolism are located in a conserved gene cluster and are induced specifically at 37ºC and during infection in fungal pathogens. Tyrosine can provide both carbon and nitrogen for growth and also results in the formation of protective melanin. The expression of tyrosine catabolic genes is under the complex control of a number of systems which respond to substrate, temperature and host signals and it is postulated that these have evolved to control the balance between growth and survival.
This work was funded by National Health and Medical Research Council of Australia and Howard Hughes Medical Institute.