Novel induction of broad-spectrum antibiotics by the human pathogen Legionella

Abstract

ABSTRACT The majority of antibiotics are natural products, with microorganism-generated molecules and their derivatives being the most prevalent source of drugs to treat infections. Thus, identifying natural products remains the most valuable resource for novel therapeutics. Here, we report the discovery of a series of dormant bacteria in honey that have bactericidal activity toward Legionella , a bacterial pathogen that causes respiratory disease in humans. We show that, in response to bacterial products secreted by Legionella , the honey bacteria release diffusible antimicrobial molecules. Remarkably, the honey bacteria only produce these molecules in response to Legionella spp., when compared to a panel of 24 bacterial pathogens from different genera. However, the molecules induced by Legionella have broad activity against several clinically important pathogens, including many high-priority pathogens. Thus, Legionella spp. are potent drivers of antimicrobial molecule production by uncharacterized bacteria isolated from honey, providing access to new antimicrobial products and an unprecedented strategy for discovering novel antibiotics. IMPORTANCE Natural products generated by microorganisms remain the most viable and abundant source of new antibiotics. However, their discovery depends on the ability to isolate and culture the producing organisms and to identify conditions that promote antibiotic production. Here, we identify a series of previously undescribed bacteria isolated from raw honey and specific culture conditions that induce the production of antimicrobial molecules that are active against a wide variety of pathogenic bacteria.