Development of Host-Cleavable Antibody-Bactericide Conjugates against Extracellular Pathogens.

Novel antimicrobial agents with potent bactericidal activity are needed to treat infections caused by multidrug-resistant (MDR) extracellular pathogens, such as . Antimicrobial peptides (AMPs) and peptidomimetics are promising alternatives to traditional antibiotics, but their therapeutic use is limited due to the lack of specificity and resulting off-target effects. The incorporation of an antibody into the drug design would alleviate these challenges by localizing the AMP to the target bacterial cells.

Lytic transglycosylases mitigate periplasmic crowding by degrading soluble cell wall turnover products.

The peptidoglycan cell wall is a predominant structure of bacteria, determining cell shape and supporting survival in diverse conditions. Peptidoglycan is dynamic and requires regulated synthesis of new material, remodeling, and turnover - or autolysis - of old material. Despite exploitation of peptidoglycan synthesis as an antibiotic target, we lack a fundamental understanding of how peptidoglycan synthesis and autolysis intersect to maintain the cell wall.