Looking beyond Typical Treatments for Atypical Mycobacteria

Abstract

The genus Mycobacterium comprises not only the deadliest of bacterial pathogens, Mycobacterium tuberculosis, but several other pathogenic species, including M. avium and M. abscessus. The incidence of infections caused by atypical or nontuberculous mycobacteria (NTM) has been steadily increasing, and is associated with a panoply of diseases, including pulmonary, soft-tissue, or disseminated infections. The treatment for NTM disease is particularly challenging, due to its long duration, to variability in bacterial susceptibility profiles, and to the lack of evidence-based guidelines. Treatment usually consists of a combination of at least three drugs taken from months to years, often leading to severe secondary effects and a high chance of relapse. Therefore, new treatment approaches are clearly needed. In this review, we identify the main limitations of current treatments and discuss different alternatives that have been put forward in recent years, with an emphasis on less conventional therapeutics, such as antimicrobial peptides, bacteriophages, iron chelators, or host-directed therapies. We also review new forms of the use of old drugs, including the repurposing of non-antibacterial molecules and the incorporation of antimicrobials into ionic liquids. We aim to stimulate advancements in testing these therapies in relevant models, in order to provide clinicians and patients with useful new tools with which to treat these devastating diseases.

Considerations for Phage Therapy Against Mycobacterium abscessus

“…Novel therapeutic options, including old drugs, iron chelators, or antimicrobial peptides show different degrees of activity against M. abscessus ( Bento et al, 2020 ; Meir and Barkan, 2020 ; Muñoz-Egea et al, 2020 ). In this review, we will focus on phage therapy as an alternative therapy against M. abscessus multiresistance.…”

Targeting Autophagy as a Strategy for Developing New Vaccines and Host-Directed Therapeutics Against Mycobacteria

“…Many studies have looked at the potential of autophagy-inducing drugs to improve current treatment regimens against mycobacteria. Due to the dramatic rise of antibiotic-resistant mycobacteria and the upsurge of NTMs that are intrinsically resistant to traditional antibiotics, host-directed therapies are even more relevant ( Deretic, 2008 ; Kim et al, 2012 ; Zullo and Lee, 2012b ; Kim et al, 2019 ; Bento et al, 2020 ).…”

“…Apoptosis and autophagy have been the most explored HDT targets of Mtb and NTMs. Even though apoptosis may be a possible target, there is mounting evidence that NTMs can escape apoptotic bodies to ensure survival and disease progression ( Early et al, 2011 ; Bento et al, 2020 ). Autophagy presents an exciting target as the induction of autophagy promotes bacterial clearance and antigen presentation ( Castillo et al, 2012 ; Saini et al, 2016 ).…”

Repurposing Avermectins and Milbemycins against Mycobacteroides abscessus and Other Nontuberculous Mycobacteria

“…Macrolide antibiotics are the backbone of current NTM therapies, typically administered in combination with amikacin [ 7 , 34 ]. However, the development of macrolide resistance occurs frequently, thus restricting their therapeutic efficacy.…”

“…NTM are an extremely diverse group, with more than 190 species currently identified and new species being frequently reported [ 7 , 8 ]. Most common diseases caused by NTM are pulmonary, disseminated, or skin and soft tissues infections [ 9 , 10 ].…”