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Comparative Analysis of an Emerging Fungal Pathogen, Penicillium marneffei

Overview

Penicillium marneffei is an emerging fungal pathogen endemic to Southeast Asia and the most prevalent Penicillium species causing fatal infections worldwide. It ranks as the third most common infection — following tuberculosis and cryptococcosis — in immunocompromised individuals in the region and its coincidence with HIV positive individuals is such that it is classified as an AIDS-defining pathogen. A number of cases of P. marneffei infection in patients with no apparent immunodeficiency have been reported, while infections in immunocompromised individuals who are not treated are universally fatal. Compounding this problem is the rate at which P. marneffei infections become resistant to the azole drugs of choice and the need for continued treatment of asymptomatic infected individuals in order to avoid relapse. Although the immunocompromised population is of particular concern with all fungal infections, studies have shown that the most alarming and marked increases in fungal infection rates have not been in transplant or oncology units but in other surgical and medical areas, demonstrating that infections are no longer restricted to the most severely immunosuppressed.

Effective control of fungal disease is hindered by the lack of a basic understanding of the biology of the fungal pathogen and its capacity to cause disease. This is in turn impeded by the lack of resources such as full genome sequences of these organisms and the ability to manipulate these genomes experimentally. Uncovering the P. marneffei genome will significantly enhance our capacity to understand the biology of this organism and its disease causing ability. Judicious comparisons of the P. marneffei genome, and subsequently its transcriptome and proteome, with that of closely related pathogenic and non-pathogenic fungi will vastly improve our understanding of the mechanisms of pathogenesis and antimycotic resistance. To achieve this goal we are sequencing the genome of P. marneffei and its closest sexual relative, Talaromyces stipitatus.

Funding

National Institute of Allergy and Infectious Disease (NIAID)