Pathogenicity and virulence of Mycobacterium tuberculosis

Abstract

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, an infectious disease with one of the highest morbidity and mortality rates worldwide. Leveraging its highly evolved repertoire of non-protein and protein virulence factors, Mtb invades through the airway, subverts host immunity, establishes its survival niche, and ultimately escapes in the setting of active disease to initiate another round of infection in a naive host. In this review, we will provide a concise synopsis of the infectious life cycle of Mtb and its clinical and epidemiologic significance. We will also take stock of its virulence factors and pathogenic mechanisms that modulate host immunity and facilitate its spread. Developing a greater understanding of the interface between Mtb virulence factors and host defences will enable progress toward improved vaccines and therapeutics to prevent and treat tuberculosis.

Keywords: Mycobacterium tuberculosis; host–pathogen interactions; infectious disease; tuberculosis; virulence factors.

Figure 1.

Overview of Mtb infection. Mtb enters the human body through the airway where it engages the innate immune system within the alveolar space. Macrophages and dendritic cells ingest the bacteria, recruiting new cells and activating adaptive immunity. Together, the innate and adaptive immune systems collaborate to eradicate the bacteria or restrict its active replication within a granuloma. Active tuberculosis occurs either after primary infection or after reactivation due to immunodeficiency, leading to symptomatic disease and transmission to a new host to start a new infection cycle.

Figure 2.

Non-protein virulence factors of Mtb. Schematic of Mtb lipids, glycolipids, glycans, and nucleic acids that contribute to virulence. TDM: trehalose dimycolate, SL-1: sulfolipid-1, PGL: phenolic glycolipid, MA: mycolic acid, PAT: pentaacyl trehalose, PDIM: phthiocerol dimycocerosates, ManLAM: mannosylated lipoarabinomannan.

Figure 3.

Protein virulence factors of Mtb. Schematic representation of Mtb interactions within infected macrophages highlighting (i) toll-like receptors, (ii) phagosome arrest and escape, (iii) autophagy subversion, (iv) cell death modulation, and (v) cytokine production. Each box contains representative Mtb virulence factors that engage host cell biologic processes detailed in the text.