Bacterial symbionts in agricultural systems provide a strategic source for antibiotic discovery

Abstract

As increased antibiotic resistance erodes the efficacy of currently used drugs, the need for new candidates with therapeutic potential grows. Although the majority of antibiotics in clinical use originated from natural products, mostly from environmental actinomycetes, high rediscovery rates, among other factors, have diminished the enthusiasm for continued exploration of this historically important source. Several well-studied insect agricultural systems have bacterial symbionts that have evolved to produce small molecules that suppress environmental pathogens. These molecules represent an underexplored reservoir of potentially useful antibiotics. This report describes the multilateral symbioses common to insect agricultural systems, the general strategy used for antibiotic discovery and pertinent examples from three farming systems: fungus-farming ants, southern pine beetles (SPBs) and fungus-growing termites.

Figure 1.

Symbiotic interactions within a generalized insect agricultural system. Arrows indicate a benefit and T-bars indicate suppression. A mutualistic symbiosis exists between the fungus and the insect. The fungus is food for the insect, and the insect provides raw materials for the fungus. The pathogen threatens the fungus, which in turn threatens the insect. The mutualistic bacteria produce antibiotics to suppress the pathogen. The insect provides nutrients and transports the bacteria.

Figure 2.

Symbiotic interactions in the Attine ant agricultural system.

Figure 3.

Structure of dentigerumycin.

Figure 4.

Symbiotic interactions in the southern pine beetle agricultural system.

Figure 5.

Structure of mycangimycin.

Figure 6.

Structures of frontalamides A and B and their biosynthetic analogs, and clifednamides A and B.

Figure 7.

Structures of microtermolides A and B.