Combating Antibiotic Resistance: Part One: Novel Antibiotic Isolation from Co-culture, Part Two: Adjuvant Chemistry

Casey Kellogg

Chemistry/Biochemistry

Amanda Wolfe

A steady decline in new antibiotic development coupled with reduced accumulation of antibiotics in Gram-negative bacteria has exacerbated antibiotic resistance resulting in a need for new methods of antibiotic development. Two methods for treating antibiotic resistant bacteria are to 1), find new antibiotics with novel mechanisms of action and 2), reactivate current antibiotics by overcoming resistance mechanisms using adjuvants. Natural products and their derivatives are the largest source of antibiotics with 73),, of approved antibacterial agents between 1981-2014 being natural product production or natural product derivatives due to their unique structural motifs. Specifically, non-pathogenic rhizosphere soil bacteria, such as Streptomyces griseus that produces the popular antibiotic streptomycin, are an important source of novel natural products. Part 1 of this work examines the co-culture of Gram-negative 415 and 565 to exploit novel natural products to inhibit pathogenic growth of Staphylococcus aureus (SA), and Escherichia coli (EC),. Part 2 focuses on improving antibiotic uptake by Gram-negative bacteria using adjuvant chemistry. The additional lipopolysaccharide outer membrane (OM), of Gram-negative bacteria increases antibiotic resistance due to impermeability and accumulation issues. It is of particular interest to target EC and ESKAPE pathogens such as Pseudomonas aeruginosa (PA), as they account for a majority of nosocomial infections. Permeability can be improved through covalently linking antibiotics to adjuvant molecules that can cross the OM. Part 2 will evaluate the use of cleavable adjuvant/antibiotic hybrids to improve antibiotic activity against EC and PA.

Jan-9-2024