Mycobacterium abscessus: It's Complex

Abstract

Mycobacterium abscessus (M. abscessus) is an opportunistic pathogen usually colonizing abnormal lung airways and is often seen in patients with cystic fibrosis. Currently, there is no vaccine available for M. abscessus in clinical development. The treatment of M. abscessus-related pulmonary diseases is peculiar due to intrinsic resistance to several commonly used antibiotics. The development of either prophylactic or therapeutic interventions for M. abscessus pulmonary infections is hindered by the absence of an adequate experimental animal model. In this review, we outline the critical elements related to M. abscessus virulence mechanisms, host-pathogen interactions, and treatment challenges associated with M. abscessus pulmonary infections. The challenges of effectively combating this pathogen include developing appropriate preclinical animal models of infection, developing proper diagnostics, and designing novel strategies for treating drug-resistant M. abscessus.

Keywords: Mycobacterium abscessus; host–pathogen interaction; novel therapeutics; pathogenesis; pulmonary infection.

Figure 1

Risk factors for NTM lung disease [6,16,31,32,33,35,36,38,40,41,42,43,44,45,46,47,48,49,50,51].

Figure 2

Genetic and acquired causes of disseminated NTM disease.

Figure 3

A schematic representation of M. abscessus current treatment protocol.

Figure 4

Mechanism of inducible resistance in M. abscessus. In M. abscessus sensu stricto and M. bolletii, macrolide binds to 23S rRNA and inhibits bacterial protein synthesis. With induction of methylase production by clarithromycin, the methylase prevents the binding of macrolide, creating an inducible resistance. Since clarithromycin induction of the ERM41 gene to produce methylase is much greater than by azithromycin, clarithromycin is much more likely to induce macrolide resistance than azithromycin.