Respiratory tract antimicrobial peptides more effectively killed multiple methicillin-resistant <i>Staphylococcus aureus</i> and nontypeable <i>Haemophilus influenzae</i> isolates after disruption from biofilm residence

Pathogenesis of most common chronic and/or recurrent bacterial diseases (e.g., middle ear infections, urinary tract infections, rhinosinusitis, among others) can be attributed to biofilms that are canonically highly resistant to both immune effectors and antibiotics. If we treat biofilms formed by diverse human pathogens with a targeted monoclonal antibody directed at protective domains of bacterial DNA-binding proteins integral to the structural stability of the eDNA-rich biofilm matrix, they are rapidly disrupted with concomitant release of the resident bacteria. These newly released (NRel) bacteria are transiently significantly more sensitive to killing by both traditional antibiotics and human PMNs, and herein, we showed that they are also more readily killed by antimicrobial peptides. Clinically, we hope to leverage this understanding of the NRel phenotype for better medical management of these challenging infections, as well as perhaps even limit or eliminate further contribution to the global antimicrobial resistance 'pandemic'.