We are currently experience a crisis of antimicrobial resistance, and the World Health Organization identified the need to combat drug resistant Gram negative pathogens as ?critical?. The last class of compounds acting against Gram negative bacteria was introduced over 50 years ago. The most effective strategy to prevent antimicrobial resistance is by introducing novel compounds that act against AMR pathogens and have low probability of resistance development. We recently identified a novel antimicrobial, teixobactin, that shows no detectable resistance against Gram positive bacteria (Ling et al., Nature 2015). Teixobactin is currently in IND-enabling development against important Gram positive AMR infections such as MRSA bacteremia. We more recently discovered another natural product antibiotic, darobactin, with unusually low resistance development that acts against Gram negative AMR pathogens. While these are encouraging advances, a considerable effort is spent on rediscovery of the same producing species and compounds. We reason that mining the rich diversity of Brazilian soils with our approaches will provide access to novel antibiotic to combat the AMR crisis. The Brazilian rain forest has the highest diversity of plants and animals, and we expect the same to be true for microorganisms. Indeed, microorganism directly or loosely associate with eukaryotes, and degrade their products. The goal of this project is to evaluate soils from Brazil for their microbial diversity, to screen isolates for compounds with Gram negative activity, and to isolate and validate novel antimicrobials. If we are able to find novel antimicrobials from soils of New England, it is reasonable to expect that the pace of discovery will increase once we access an environment with the richest diversity on the planet. This project brings together Dr. Kim Lewis, Northeastern University, an expert in drug resistance and drug discovery, and Dr. Monica Pupo, University Sao Paulo, an expert in natural products chemistry. These scientists collaborated on writing the proposal and will work closely together on its execution.
The goal of this project is to discover novel antibiotics acting against important drug resistant Gram negative pathogens. For this, we will apply a unique focused screening we developed, to a rich source of biodiversity ? soils and sediment samples from Brazil.