Identifying Opportunity Targets in Gram-Negative Pathogens for Infectious Disease Mitigation.

Antimicrobial drug resistance (AMR) is a pressing global human health challenge. Humans face one of their grandest challenges as climate change expands the habitat of vectors that bear human pathogens, incidences of nosocomial infections rise, and new antibiotics discovery lags. AMR is a multifaceted problem that requires a multidisciplinary and an "all-hands-on-deck" approach. As chemical microbiologists, we are well positioned to understand the complexities of AMR while seeing opportunities for tackling the challenge. In this Outlook, we focus on vulnerabilities of human pathogens and posit that they represent "opportunity targets" for which few modulatory ligands exist. We center our attention on proteins in Gram-negative organisms, which are recalcitrant to many antibiotics because of their external membrane barrier. Our hope is to highlight such targets and explore their potential as "druggable" proteins for infectious disease mitigation. We posit that success in this endeavor will introduce new classes of antibiotics that might alleviate some of the current pressing AMR concerns.