Actinobacteria are a ubiquitous, diverse, and very successful group of bacteria occupying a large number of different niches and taking many different forms, although all are Gram-positive (having tough outer coats that absorb the blue dye in Gram staining), which indicates that they were among the earliest inhabitants of Earth. Pseudonocardia, which resemble fungi in their filamentous form, are soil dwellers, and soil is a busy, competitive place—a perfect laboratory for the creation of small molecules, some of which have been adapted by humans, along with ants, for use as antibiotics. Indeed, four of the best-known human antibiotics —actinomycin, neomycin, streptomycin, and vancomycin— were derived from actinobacteria.
One of the Pseudonocardia-manufactured chemical weapons that attine ants use to protect their fungal gardens was described in 2009. Called “dentigerumycin” in honor of Apterostigma dentigerum, the ant that helped choreograph its evolution, this small molecule (molecular formula: C40H67N9O13) actively inhibits Escovopsis, but largely spares the ant’s garden fungi. Dentigerumycin, a cyclic depsipeptide (a peptide with one or more ester bonds in addition to the amide bonds) containing unusual amino acids, also slows the growth of a multidrug-resistant strain of the human pathogen Candida albicans and may provide humans with an antifungal alternative to existing drugs.
Escovopsis, like Candida, can develop antibiotic resistance, but Pseudonocardia have millions of years of experience evolving new small molecules and usually outpace the fungus. In the event that this does not happen fast enough, the ants simply acquire new strains of actinobacteria, possibly from other symbiotic stock or the soil surrounding their nests. Researchers, however, are not yet able to fully explain how this is done. But, it appears that leaf-cutting ants tamed free-living strains of Pseudonocardia many times over during the course of their long evolutionary history together and that the acquisition is very selective; actinobacteria are the only clearly established symbionts of fungusgrowing ants.
Understanding the chemistry underlying all that Pseudonocardia do for the ants is a major research issue and will ultimately yield important insights about how they and bacteria in general deal with the world. For example,
biosynthetic pathways called “orphan pathways” are turned on in special and completely unknown circumstances and it is important to know how and why this happens. Moreover, it is unlikely that Pseudonocardia developed the small molecules that the ants use as antibiotics for the express purpose of warding off the ants’ garden parasites; they probably have more peaceful uses in the wild. Bacteria tend to be gregarious, gathering in high-density populations, probably reflecting a safety in numbers strategy. Furthermore, they “chatter” continuously and their words are chemical. Thus, one important use for the actinobacterial small molecules is probably “quorum sensing,” a bacterial monitoring language that tells them how many and what type of microbes are gathered in their neighborhood. Genome sequencing is needed to define the small molecule-generating potential of Pseudonocardia; analytical chemistry is needed to isolate and characterize the molecules themselves; and functional assays are necessary to determine what these molecules actually do. The sequencing began in earnest in 2009, with three ant genomes and 14 ant-associated fungal and bacterial genomes under active investigation. Finalizing the genome sequences and annotation will take years, but results are being made available to the scientific community as they progress.
Decoding Science. One article at a time.