Monoclonal antibodies against DNA-binding tips of DNABII proteins disrupt biofilms in vitro and induce bacterial clearance in vivo

• Monoclonal antibodies (MAbs) against protective epitopes of a DNABII protein disrupted diverse bacterial biofilms in vitro.
• Delivery of these MAbs also provided therapeutic efficacy in two animal models of biofilm infection.
• Bacteria newly released from the biofilm by the action of the MAbs were susceptible to host-mediated clearance and tobramycin.Research In ContextThe bacteria which cause the vast majority of chronic and recurrent diseases characteristically form ‘biofilms’. Biofilms are communities of bacteria with many unique properties, including being highly resistant to antibiotics and the body's immune response. To develop an effective therapeutic for biofilm infections, we targeted the DNABII proteins, a universal biofilm component that provides structural integrity. Monoclonal antibodies against domains of the DNABII proteins induced complete collapse of diverse biofilms with release of resident bacteria that were highly susceptible to killing by host immune effectors and traditional antibiotics. This therapeutic also mediated resolution of infection in two experimental animal models.

The vast majority of chronic and recurrent bacterial diseases are attributed to the presence of a recalcitrant biofilm that contributes significantly to pathogenesis. As such, these diseases will require an innovative therapeutic approach. We targeted DNABII proteins, an integral component of extracellular DNA (eDNA) which is universally found as part of the pathogenic biofilm matrix to develop a biofilm disrupting therapeutic. We show that a cocktail of monoclonal antibodies directed against specific epitopes of a DNABII protein is highly effective to disrupt diverse biofilms in vitro as well as resolve experimental infection in vivo, in both a chinchilla and murine model. Combining this monoclonal antibody cocktail with a traditional antibiotic to kill bacteria newly released from the biofilm due to the action of the antibody cocktail was highly effective. Our results strongly support these monoclonal antibodies as attractive candidates for lead optimization as a therapeutic for resolution of bacterial biofilm diseases.