Aligning Antimicrobial Drug Discovery with Complex and Redundant Host-Pathogen Interactions

Drug-resistant microorganisms pose an enormous threat to public health. Here we provide examples of experimental approaches that offer novel ways to think about drug development considering the complexity inherent to host-pathogen interactions. Emergent themes include (1) targeting pathogenicity rather than microbial growth, (2) targeting the host or host-pathogen interface rather than the pathogen, (3) facilitating pathogen-specific immune responses, and (4) utilizing systems-based approaches to identify new drug targets and validate drug efficacy. We posit that together these approaches may allow identification of drugs that disrupt pathogenesis and allow the immune system time to protect, but do not easily engender resistance.