Mycobacterium abscessus: Environmental Bacterium Turned Clinical Nightmare

Abstract

Mycobacteria are a large family of over 100 species, most of which do not cause diseases in humans. The majority of the mycobacterial species are referred to as nontuberculous mycobacteria (NTM), meaning they are not the causative agent of tuberculous (TB) or leprosy, i.e., Mycobacterium tuberculous complex and Mycobacterium leprae, respectively. The latter group is undoubtedly the most infamous, with TB infecting an estimated 10 million people and causing over 1.2 million deaths in 2017 alone TB and leprosy also differ from NTM in that they are only transmitted from person to person and have no environmental reservoir, whereas NTM infections are commonly acquired from the environment. It took until the 1950′s for NTM to be recognised as a potential lung pathogen in people with underlying pulmonary disease and another three decades for NTM to be widely regarded by the medical community when Mycobacterium avium complex was identified as the most common group of opportunistic pathogens in AIDS patients. This review focuses on an emerging NTM called Mycobacterium abscessus (M. abs). M. abs is a rapidly growing NTM that is responsible for opportunistic pulmonary infections in patients with structural lung disorders such as cystic fibrosis and bronchiectasis, as well as a wide range of skin and soft tissue infections in humans. In this review, we discuss how we came to understand the pathogen, how it is currently treated and examine drug resistance mechanisms and novel treatments currently in development. We highlight the urgent need for new and effective treatments for M. abs infection as well as improved in vivo methods of efficacy testing.

The Peroxisome Proliferator-Activated Receptor α- Agonist Gemfibrozil Promotes Defense Against Mycobacterium abscessus Infections

“…However, little is known about the host factors that influence the pathogenesis of NTM infection [1,3,4]. Mycobacterium abscessus (Mabc), a rapidly growing NTM species, lives in natural environments such as water and soil, and causes pulmonary, cutaneous, and other opportunistic infectious diseases [3,5]. Although the pulmonary infection caused by Mabc progresses slowly, it is often virulent and difficult to treat with antimicrobials due to its resistance to most antibiotic classes [5].…”

“…Mycobacterium abscessus (Mabc), a rapidly growing NTM species, lives in natural environments such as water and soil, and causes pulmonary, cutaneous, and other opportunistic infectious diseases [3,5]. Although the pulmonary infection caused by Mabc progresses slowly, it is often virulent and difficult to treat with antimicrobials due to its resistance to most antibiotic classes [5]. A better understanding of host defense mechanisms is needed to develop novel control strategies against infection with Mabc and other NTM.…”

Aggregation of nontuberculous mycobacteria is regulated by carbon:nitrogen balance

“…Understanding the environmental niches in which NTM have evolved can lend context to our finding that C:N balance controls aggregation state. NTM are non-motile saprophytes that are common residents of soil and waterways (22, 28, 44). In soil, carbon is most often the limiting nutrient for bacterial growth (45, 46).…”

“…It is worth exploring whether nodes along such a pathway could be identified and exploited as new targets for biofilm control. The rising threat of NTM infections, particularly to susceptible communities such as CF patients, as well as the correlation between increased aggregation and virulence, lends motivation to further probe the mechanisms of aggregation and dispersal in these pathogens (19, 21, 27, 28).…”

“…NTM can infect healthy adults after repeated exposure and are especially dangerous to immunocompromised populations and patients with lung disorders such as Cystic Fibrosis (CF) and Chronic Obstructive Pulmonary Disease (COPD) (23–26). Infections with NTM can be very difficult to treat; M. abscessus lung infections, in particular, require long courses of antibiotic cocktails that have limited efficacy and extensive adverse side effects (24, 27, 28). The ability of M. abscessus to aggregate into cord-like aggregates correlates with increased pathogenicity in a zebrafish model and an enhanced ability to evade phagocytosis (19–21), indicating that the formation of multicellular structures by NTM is positively related to their sustained infection of hosts.…”