Towards enhanced translational value: preclinical drug activity testing against actively multiplying, nutrient-starved and pellicle biofilm-embedded Mycobacterium abscessus.

BACKGROUND AND

OBJECTIVES

Mycobacterium abscessus can cause severe infections in at-risk patients. Treatment efficacy for M. abscessus infections remains low, and better treatment options are needed. Factors hampering antibiotic potency may include the ability of M. abscessus to form biofilms and to endure in nutrient-deprived environments. These factors are underrepresented in current preclinical drug activity assays. Diversifying preclinical models by incorporating characteristics of these harsh environments may be important to better predict drug efficacy in patients. We aimed to develop a novel tool for studying drug activity against biofilm-embedded M. abscessus. In addition, drug activity was assessed against actively multiplying and nutrient-starved M. abscessus.

METHODS

An in-house 3D-printed platform-disc-based biofilm model was developed to study M. abscessus pellicle biofilms. In vitro activity of 16× the MICs of amikacin, bedaquiline, clofazimine, imipenem, rifabutin and tigecycline was assessed using time-kill kinetics assays.

RESULTS

The platform-disc-based model established reliable and reproducible quantification of M. abscessus biofilms. Drug activity against biofilm-embedded and nutrient-starved M. abscessus seemed less pronounced than against actively multiplying mycobacteria. For biofilm-embedded M. abscessus, drug activity was dependent on the developmental stage of the biofilm.

CONCLUSIONS

The varying levels of drug activity observed across the different M. abscessus populations highlight their distinct physiological relevance. As such, the platform-disc-based biofilm model could serve as a valuable asset in preclinical drug activity assays for M. abscessus.