Virulence-Associated Secretion in Mycobacterium abscessus

Abstract

Non-tuberculous mycobacteria (NTM) are a heterogeneous group of originally environmental organi3sms, increasingly recognized as pathogens with rising prevalence worldwide. Knowledge of NTM's mechanisms of virulence is lacking, as molecular research of these bacteria is challenging, sometimes more than that of M. tuberculosis (Mtb), and far less resources are allocated to their investigation. While some of the virulence mechanisms are common to several mycobacteria including Mtb, others NTM species-specific. Among NTMs, Mycobacterium abscessus (Mabs) causes some of the most severe and difficult to treat infections, especially chronic pulmonary infections. Mabs survives and proliferates intracellularly by circumventing host defenses, using multiple mechanisms, many of which remain poorly characterized. Some of these immune-evasion mechanisms are also found in Mtb, including phagosome pore formation, inhibition of phagosome maturation, cytokine response interference and apoptosis delay. While much is known of the role of Mtb-secreted effector molecules in mediating the manipulation of the host response, far less is known of the secreted effector molecules in Mabs. In this review, we briefly summarize the knowledge of secreted effectors in Mtb (such as ESX secretion, SecA2, TAT and others), and draw the parallel pathways in Mabs. We also describe pathways that are unique to Mabs, differentiating it from Mtb. This review will assist researchers interested in virulence-associated secretion in Mabs by providing the knowledge base and framework for their studies.

Keywords: abscessus; macrophage; mycobacteria; secretion; virulence.

Figure 1

Visual summary of the secreted effectors in Mtb and Mabs and their intracellular targets. Once the bacilli are phagocytosed by the macrophage, it goes through a series of processing stages: early and late phagosome formation, phagosome acidification and phago-lysosome fusion. Necrosis is an undesirable outcome for the host, while it promotes cell-to-cell spread of the bacteria. Apoptosis, while leading to macrophage death, promotes effective immune response, and is therefore detrimental to the bacteria in the infection process. During each stage, the mycobacteria attempts to block phagosome maturation and acidification, prevent apoptosis and promote necrosis. Effectors are marked in green when a MABS analog of the Mtb protein is either identified or is presumed to exist, and in red when no MABS analog has been identified or suggested.