Mycobacterium abscessus biofilm cleared from murine lung by monoclonal antibody against bacterial DNABII proteins

Abstract

Background

Pulmonary infections with multidrug-resistant nontuberculous mycobacteria (NTM), particularly Mycobacterium abscessus (MAB), are increasingly more prevalent in individuals with lung disease such as cystic fibrosis and are extremely difficult to treat. Protracted antibiotic therapies consist of multidrug regimens that last for months to years. Despite these intense protocols, failure rates are high with 50%-60% of patients not achieving a sustained culture-negative status. A major contributor to the difficult medical management of NTM infections is formation of pulmonary aggregate MAB biofilms which protect the resident bacteria from antimicrobials and host immune effectors. Thereby, novel and more effective approaches to combat recalcitrant NTM infections are urgently needed.

Methods

We developed an epitope-targeted monoclonal antibody-based technology to rapidly disrupt biofilms and release resident bacteria into a transient yet highly vulnerable phenotype that is significantly more sensitive to killing by both antibiotics and host innate immune effectors (e.g., PMNs and antimicrobial peptides). Herein, we tested this technology in a pre-clinical murine lung infection model to determine whether this treatment would mediate clearance of MAB from the lungs and speed return to homeostasis.

Results

As early as 48 h after a single treatment, bacterial loads were reduced to below the level of detection and histopathologic analysis showed markedly decreased inflammation and rapid eradication of aggregate biofilms compared to controls.

Conclusions

These new data add to those from multiple prior published studies which show the significant efficacy of this novel therapeutic approach to resolve recalcitrant bacterial biofilm diseases, now potentially including those induced by NTM.