We develop new antibiotics and design new approaches for the in vitro evaluation of antibiotics.
“Bad bugs, no drugs: As antibiotic research stagnates, a public health crisis brews” was the title of a policy report from the Infectious Disease Society of America published in 2004, a report which outlined the consequences of alarming rates of antibiotic resistance and the dire need for a reinvestment in the search for new antibiotics to overcome the exceedingly lean development pipeline. Updates in 2008 and 2013 showed that while some progress was being made the need for new compounds was still unmet. As very few drugs (linezolid, daptomycin, televancin, tigecycline) that are not analogs of well-established drugs have been introduced in the last twenty-five years the case for developing new antibiotic classes is a compelling one.
New classes of antibiotics
We have developed a new approach to generate novel, natural product-like structures in a combinatorial fashion – ReBACS: Recombinant Biotechnology Assisted Combinatorial Synthesis. Using a synergy between fermentation technology, biosynthetic engineering and chemical synthesis we can generate large arrays of New Chemical Entities (NCEs) that bridge the structural complexity of natural products with the diversity attainable through synthetic modification.

A complete proof-of-concept and major milestone in this work was achieved with the discovery of the triazolononactates, a novel structural class of antibiotics that are effective against drug resistant Gram-positive pathogens.
New delivery systems
Patient compliance is critical to positive outcomes in antibiotic therapy. The longer the course of therapy, or the more doses necessary, the less likely good compliance is to be achieved which promotes the rise of antibiotic resistance. Our goal is to develop new, single dose antibiotic formulations. Our work, in collaboration with The University of Montana, is developing thixotropic hydrogels as antibiotic delivery systems. The gels liquefy on shaking and re-gel upon standing. These properties are perfectly matched for the treatment of ear infections (otitis externa) – imagine an antibiotic-containing gel that, once shaken, is liquid and can be placed in the ear, whereupon standing it gels. The antibiotic is slowly released from the gel over the course of the therapy, a therapy requiring a single treatment.
New in vitro PK analyses to replace animal models
Reduce, refine and replace – these are the significant considerations when planning experiments that use animals. The contributions of animal research to antibiotic research cannot be understated or denied and yet such experiments remain controversial because the animals can feel fear and pain. We have developed a new approach to in vitro pharmaceutics experiments that replaces the animal, generates more accurate and larger quantities of data and allows for significant reduction and replacement of animals in antibiotic discovery programs. Our system allows for proof of concept, dose optimization, pharmaceutic analysis and resistance profiling of a new antibiotic. It provides insight into efficacy studies. It greatly reduces cost and regulatory overhead.
New takes on old antibiotics to overcome resistance
Bactrim is a mixture of sulfamethoxazole and trimethoprim, the latter being an inhibitor of the enzyme dihydrofolate reductase (DHFR). In 2016 alone there were over six million prescriptions written for Bactrim in the US. Unfortunately, for such a useful antibiotic, resistance is on the rise. We have had a longstanding and exceptionally productive collaboration with the University of Connecticut new analogs of trimethoprim which, in 2016, culminated in a licensing deal with Spero Therapeutics.