In:
mBio, American Society for Microbiology, Vol. 8, No. 4 ( 2017-09-06)
Abstract:
Fungal diseases are estimated to kill between 1.5 and 2 million people each year, which exceeds the global mortality estimates for either tuberculosis or malaria. Only four classes of antifungal agents are available to treat invasive fungal infections, and all suffer pharmacological shortcomings, including toxicity, drug-drug interactions, and poor bioavailability. There is an urgent need to develop a new class of drugs that operate via a novel mechanism of action. We have identified a potential drug target, PptA, in the fungal pathogen Aspergillus fumigatus . PptA is required to synthesize the immunotoxic compound gliotoxin, DHN-melanin, which A. fumigatus employs to evade detection by host cells, the amino acid lysine, and the siderophores TAFC and FC, which A. fumigatus uses to scavenge iron. We show that strains lacking the PptA enzyme are unable to establish an infection, and we present a method which we use to identify novel antifungal drugs that inactivate PptA.
Type of Medium:
Online Resource
ISSN:
2161-2129
,
2150-7511
DOI:
10.1128/mBio.01504-16
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2017
detail.hit.zdb_id:
2557172-2
Permalink