The Human Microbiome as a Focus of Antibiotic Discovery: Neisseria mucosa Displays Activity Against Neisseria gonorrhoeae

Abstract

<i>Neisseria gonorrhoeae</i> infections are a serious global health problem. This organism has developed disturbing levels of antibiotic resistance, resulting in the need for new approaches to prevent and treat gonorrhea. The genus <i>Neisseria</i> also includes several members of the human microbiome that live in close association with an array of microbial partners in a variety of niches. We designed an undergraduate antibiotic discovery project to examine a panel of nonpathogenic <i>Neisseria</i> species for their ability to produce antimicrobial secondary metabolites. Five strains belonging to the <i>N. mucosa</i> species group displayed activity against other <i>Neisseria</i> in delayed antagonism assays; three of these were active against <i>N. gonorrhoeae</i>. The antimicrobial compound secreted by <i>N. mucosa</i> NRL 9300 remained active in the presence of catalase, trypsin, and HEPES buffer, and effectively inhibited a DNA uptake mutant of <i>N. gonorrhoeae</i>. Antimicrobial activity was also retained in an ethyl acetate extract of plate grown <i>N. mucosa</i> NRL 9300. These data suggest <i>N. mucosa</i> produces an antimicrobial secondary metabolite that is distinct from previously described antigonococcal agents. This work also serves as a demonstration project that could easily be adapted to studying other members of the human microbiome in undergraduate settings. We offer the perspective that both introductory and more advanced course-based and apprentice-style antibiotic discovery projects focused on the microbiome have the potential to enrich undergraduate curricula and we describe transferrable techniques and strategies to facilitate project design.