Abstract
The clinically important Mycobacterium tuberculosis (M. tb) and related mycobacterial pathogens use various virulence mechanisms to survive and cause disease in their hosts. Several well-established virulence factors include the surface-exposed lipids in the mycobacterial outer membrane, as well as the Esx family proteins and the Pro-Glu (PE)/ Pro-Pro-Glu (PPE) family proteins secreted by type VII secretion systems (T7SS). Five ESX T7SS exist in M. tb and three—EsxA secretion system-1 (ESX-1), ESX-3, and ESX-5—have been implicated in virulence, yet only the structures of ESX-3 and ESX-5 have been solved to date. Here, we summarize the current research on three outer membrane lipids—phthiocerol dimycocerosates, phenolic glycolipids, and sulfolipids—as well as the secretion machinery and substrates of three mycobacterial T7SS—ESX-1, ESX-3, and ESX-5. We propose a structural model of the M. tb ESX-1 system based on the latest structural findings of the ESX-3 and ESX-5 secretion apparatuses to gain insight into the transport mechanism of ESX-associated virulence factors.
Highlights
The host–pathogen relationship between humans and Mycobacterium tuberculosis (M. tb) has been evolving for approximately 50,000 to 70,000 years [1], and its persistence as an infectious pathogen has led to 10 million new cases of tuberculosis (TB) and 1.2 million TB-related deaths in 2018 [2]
M. tb and related mycobacterial pathogens use a complex assortment of virulence factors to cause
M. tb and related mycobacterial pathogens use a complex assortment of virulence factors to disease in their hosts, which are not limited to surface-exposed lipids and secreted proteins
Summary
The host–pathogen relationship between humans and Mycobacterium tuberculosis (M. tb) has been evolving for approximately 50,000 to 70,000 years [1], and its persistence as an infectious pathogen has led to 10 million new cases of tuberculosis (TB) and 1.2 million TB-related deaths in 2018 [2]. TB disease [8], but they can lead to extrapulmonary disease when bacteria disseminate outside of the lungs, such as to the central nervous system and/or lymph nodes [9] Another class of clinically relevant mycobacteria includes non-tuberculosis mycobacteria such as the M. avium complex [10,11], M. marinum [12,13], and M. ulcerans [14], which are opportunistic pathogens that can cause disease in immunocompromised individuals. Sci. 2020, 21, 3985 host, it is considered a virulence factor Some of these factors have been identified by genomic, biochemical, and functional analysis of M. tb and related mycobacterial pathogens, several itofisthese considered factor. Some that of these have been identified by genomic, genes aorvirulence cellular components havefactors well-recognized roles in virulence willbiochemical, be the focus and functional analysis of.
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