A call to arms: Mustering secondary metabolites for success and survival of an opportunistic pathogen

• DOI: 10.1371/journal.ppat.1007606
• Publication Date: 2019-04-04T17:26:59Z
• Authors: Nicholas Raffa; Nancy P. Keller
• Keywords: Human pathogen

Aspergillus fumigatus is a ubiquitous saprophytic mold able to grow on diversity of material ranging from decayed organic matter in the environment space station cupolas [1]. Yet this fungus equally adept as serious opportunistic pathogen, causing pulmonary aspergillosis and more deadly invasive (IA). There are an estimated 3,000,000 cases annually than 200,000 IA each year reaching mortality rate up 90% most susceptible populations [2]. Difficulties treating include delayed detection increasing resistance antifungal treatment. Like many fungi, there no one gene that makes A. such threatening pathogen. One unique feature pathogen its arsenal small molecules impact disease development. Secondary metabolites characterized bioactive low molecular weight not required for growth organism but instead aid survival harsh environments, resisting desiccation UV stress improving competition with other microbes. For fumigatus, these benefits extend aiding only human body well. Some secondary combat host immune system by affecting cell function or shielding against attack, whereas others allow acquire essential, scarce cofactors. The following synopsis produced highlights how microbial metabolites, although undoubtedly evolved environmental protectants, can infectious development (Fig 1). Although we delineate roles metabolite category ease discussion (e.g., “on offensive,” “scavenging battlefield,” “arms race”), reader should note may have several biological fungus, part illustrated Fig 1.

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Fig 1

Roles metabolites. A list flanked their proposed (right) (left). Metabolites “?” indicate compound has been examined niche. Bracketed numerals [22]) reference associated role metabolite. Nidulanin A all end-product biosynthetic cluster. ROS, reactive oxygen species; TNF-α, tumor necrosis factor alpha.