Microbial symbionts of marine invertebrates for antibiotic discovery

DESCRIPTION provided by applicant The overall goal of this project is to discover novel antibiotics to combat important drug resistant pathogens One effective countermeasure against such pathogens is novel antibiotics but the rate of antibiotic discovery has been in steady decline All the more recently introduced antibiotics are derivatives of older antibiotics or resulted from revival of initially discarded compounds which were discovered decades ago such as daptomycin linezolid synercid and fidaxomycin Clinically used antibiotics have traditionally been discovered by screening for active secondary metabolites of readily culturable microorganisms This resource represents andlt of all microbial diversity in nature The other andgt unexplored and previously unavailable microorganisms are arguably the single most promising resource for novel antibiotics NovoBiotic directly addresses the bottleneck of antibiotic discovery by using unique cultivation approaches the diffusion chamber and trap methodologies to isolate previously andquot uncultivableandquot microorganisms This approach has resulted in new compounds so far at a rate far higher than the predicted industry standard Several of these compounds are of principal novelty and are in development including Novo a DNA G quadruplex binder currently in development as an anti cancer agent in collaboration with the National Cancer Institute Novo a macrolactam inhibitor of cell wall biosynthesis lassomycin an inhibitor of the essential ClpP P C protease of M tuberculosis and teixobactin a novel cell wall synthesis inhibitor This project takes the next step and extends the technology to shallow water marine invertebrate microbe symbioses ubiquitously present and easily accessible in local communities From the limited exploration conducted to date a number of bioactive compounds with unique properties have been discovered from marine symbioses including anti tumor and anti microbial compounds There is strong evidence that it is the associated microorganisms living in association with the host invertebrates that produce the bioactive compounds We will develop our methods to isolate novel microbial species living in association with marine invertebrates and screen these strains for antimicrobial activity We will compare the diversity and novelty of active compounds from strains isolated from the diffusion chamber trap and conventional plating The end result of this Phase I project will be proof of concept of new technologies to discover antibiotics from a poorly explored source of microbial diversity formerly andquot uncultivableandquot microbial species from marine invertebrate microbe symbioses PUBLIC HEALTH RELEVANCE It is widely recognized that new antibiotics are needed to combat drug resistant bacterial infections The proposed study will exploit the previously inaccessible microbial diversity of marine invertebrate symbionts to discover novel antibiotics