Many serious
bacterial infections are
antibiotic refractory due to biofilm formation. A key structural component of biofilm is extracellular
DNA, which is stabilized by
bacterial proteins, including those from the DNABII family.
TRL1068 is a high-affinity human
monoclonal antibody against a DNABII
epitope conserved across both Gram-positive and Gram-negative bacterial species. In the present study, the efficacy of
TRL1068 for the disruption of biofilm was demonstrated in vitro in the absence of
antibiotics by scanning electron microscopy. The in vivo efficacy of this antibody was investigated in a well-characterized
catheter-induced aortic valve
infective endocarditis model in rats infected with a methicillin-resistant Staphylococcus aureus (MRSA) strain with the ability to form thick biofilms, obtained from the blood of a patient with persistent clinical
infection. Animals were treated with
vancomycin alone or in combination with
TRL1068. MRSA burdens in cardiac vegetations and within
intracardiac catheters, kidneys, spleen, and liver showed significant reductions in the combination arm versus
vancomycin alone (P < 0.001). A trend toward mortality reduction was also observed (P = 0.09). In parallel, the in vivo efficacy of
TRL1068 against a multidrug-resistant clinical Acinetobacter baumannii isolate was explored by using an established mouse model of skin and soft tissue
catheter-related biofilm
infection.
Catheter segments infected with A. baumannii were implanted subcutaneously into mice; animals were treated with
imipenem alone or in combination with
TRL1068. The combination showed a significant reduction of
catheter-adherent bacteria versus the
antibiotic alone (P < 0.001).
TRL1068 shows excellent promise as an adjunct to standard-of-care
antibiotics for a broad range of difficult-to-treat
bacterial infections.