The development of bacterial pathogens for use as biodefense agents poses a severe threat to national security, as these microorganisms are evolving resistance to known antibiotics and are able to efficiently infect and kill humans. Ten of the fourteen genera of bacteria on the NIAID Priority Pathogens list are Proteobacteria, a group that is ubiquitous in aquatic environments. In the current study, we hypothesize that the production of antimicrobial secondary metabolites may be induced by direct competition experiments between neighboring environmental bacteria in liquid co-culture. We selected 110 aquatic actinomycete strains that did not produce antibiotics in liquid culture. We then co-cultured each of these with Proteobacteria from four biodefense-related genera (Yersinia, Brucella, Burkholderia, and Xanthomonas) and evaluated the antibiotic activity of the resulting culture extracts. In preliminary experiments, we observed that the co-culture of actinomycete strain B033 with Burkholderia vietnamiensis resulted in the production of the antibiotic resistomcyin. Importantly, this secondary metabolite was not observed in the culture broth of actinomycete control. We are currently exploring whether the induction of resitomycin is specific to microbial co-culture. However, it is evident from our initial screening results that antibiotics can be induced from actinomycete strains whose culture extracts are presumptively void of antibiotic activity. Whether this method is an effective means to discover antibiotics to treat infections caused by biodefense agents is yet to be determined, and will be discussed herein. In general, our experiments support the widely claimed potential of bacterial genomes to produce 'cryptic metabolites' in response to stress.