Preclinical murine models to study lung infection with Mycobacterium abscessus complex

Abstract

Mycobacterium abscessus is a non-tuberculous mycobacterium (NTM) able to cause invasive pulmonary infections, named NTM pulmonary disease. The therapeutic approaches are limited, and infections are difficult to treat due to antibiotic resistance conferred by an impermeable cell wall, drug efflux pumps, or drug-modifying enzymes. The development of new therapeutics, intended as antimicrobials or drug limiting immunopathology, is urgently necessary. In this context, the preclinical murine models of M. abscessus represent a useful tool to validate and translate in vitro-proofed concepts. These in vivo models are essential for developing new targets and drugs, ameliorating our knowledge in combinatorial regimens of current existing antibiotic treatments, and repurposing existing drugs for new therapeutic options against M. abscessus infection. Thus, this review aims at providing an overview of the current state of the art of preclinical murine models to study M. abscessus lung infection and its exploitation for new therapeutic approaches. This review discusses the murine models available focusing on the different bacterial challenges (aerosol, intranasal, intratracheal, and intravenous administrations), murine genetic background, and additional bacterial related factors. Then, we discuss the successful preclinical models for M. abscessus respiratory infection exploited to study the efficacy and safety of new antimicrobials or to determine the best dosage and route of administration of existing drugs. Finally, we present the current murine models exploited to develop new therapeutic approaches to modulate the host immune response and limit immunopathological damage during M. abscessus lung disease. In conclusion, our review article provides an overview of current and available murine models to characterize acute or chronic infections and to study the outcome of new therapeutic strategies against M. abscessus lung infection.