Chemical warfare: The battle between termite-associated actinobacteria and Trichoderma harzianum, a fungal pathogen

Termite-associated actinobacteria are prolific producers of biologically active small molecules that exhibit a range of potencies against pathogenic microbes, including Trichoderma harzianum, a common biocontrol agent [1]. This constant exposure to antimicrobial agents pressures the pathogens to evolve a defense mechanism in order to counteract the antagonism. These mechanisms including detoxifying the agent, increasing the number of active efflux pumps to remove the toxin, or by switching 'on' a cryptic or silent gene cluster that encodes for an antibacterial agent [2]. Our recent study elucidated a chemical conversation between the fungal pathogen, T. harzianum, and a termite-associated actinobacteria, revealing a likely co-evolution of defense metabolites. We have found that a bacterial antifungal agent – bafilomycin C1 – up-regulates the production of several metabolites in the fungal pathogen, including a metabolite that exhibits strong antibacterial activity. Identification of these up-regulated metabolites was accomplished by growing the fungal pathogen on solid media that was conditioned with bafilomycin C1. Three major metabolites were identified, all of which loosely resemble the azaphilone family of metabolites. Two of the structures are novel, one of which is quite interesting as it is highly hydrogen deficient as evident by a molecular formula of C28H26O8 (MF for the two additional metabolites are C13H18O2 and C19H20O6). Traditional structure elucidation using 2D NMR was unsuccessful due to the high degree of quaternary carbons (15 in total) and oxygen atoms. However, through the utilization of a computer-assisted structure elucidation program in collaboration with ACD/labs, we have proposed a likely structure representing a new carbon backbone [3]. Overall, this project illuminated the chemical warfare ongoing between termite-associated Streptomyces and a fungal pathogen, yielding a small glimpse of the complex interactions constantly occurring between microbes within the termite nests.