The cell surface adhesins of Mycobacterium tuberculosis

Vinod, Vivek; Vijayrajratnam, Sukhithasri; Vasudevan, Anil; Biswas, Raja

doi:10.1016/j.micres.2019.126392

Cited by 31 publications

(20 citation statements)

References 100 publications

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“…Both secretion pathways can contribute to virulence and subverting the host immune system in Mtb ( 52 ). The major subtype-dependent differences between the PBFs and SBFs were related to invasion and adherence, including the MCE proteins, fibronectin-binding APA, and HphA, which can modulate host cell signaling as well as aid adhesion or entry into host cells ( 53 – 55 ). All these proteins were significantly more produced by the PBFs than the SBFs, and, in the case of MCEs, may also involve MVs, as these adhesins are located on the inner membrane of the mycobacterial cell wall.…”

Section: Discussionmentioning

confidence: 99%

Surface-Shaving Proteomics of Mycobacterium marinum Identifies Biofilm Subtype-Specific Changes Affecting Virulence, Tolerance, and Persistence

et al. 2021

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Mycobacteria are naturally resilient, and mycobacterial infections are notoriously difficult to treat with antibiotics, with biofilm formation being the main factor complicating the successful treatment of tuberculosis (TB). The present study shows that nontuberculous Mycobacterium marinum ATCC 927 forms submerged- and pellicle-type biofilms with lichen- and ribbon-like structures, respectively, as well as persister cells under the same conditions.

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Section: Discussionmentioning

confidence: 99%

Surface-Shaving Proteomics of Mycobacterium marinum Identifies Biofilm Subtype-Specific Changes Affecting Virulence, Tolerance, and Persistence

et al. 2021

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“…Both secretion pathways can contribute to virulence and subverting the host immune system in Mtb (52). The major subtype-dependent differences between the PBFs and SBFs were related to invasion and adherence, including the MCE proteins, fibronectin binding APA and HphA, which can modulate host cell signaling as well as aid adhesion or entry into host cells (53-55). All these proteins were significantly more produced on the PBFs than the SBFs, and, in the case of MCEs, may also involve MVs, as these adhesins are located on the inner membrane of the mycobacterial cell wall.…”

Section: Discussionmentioning

confidence: 99%

Surface-Shaving Proteomics ofMycobacterium marinumIdentifies Biofilm Subtype-Specific Changes Affecting Virulence, Tolerance and Persistence

Savijoki

Myllymäki

Luukinen

et al. 2021

Preprint

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The complex cell wall and biofilm matrix (ECM) act as key barriers to antibiotics in mycobacteria. Here, the ECM-proteins of Mycobacterium marinum ATCC927, a non-tuberculous mycobacterial model, was monitored over three months by label-free proteomics and compared with cell-surface proteins on planktonic cells to uncover pathways leading to virulence, tolerance, and persistence. We show that ATCC927 forms pellicle-type (PBFs) and submerged-type (SBFs) biofilms after two weeks and two days of growth, respectively, and that the increased CelA1 synthesis in this strain prevents biofilm formation and leads to reduced rifampicin tolerance. The proteomic data suggests that specific changes in mycolic acid synthesis (cord factor), Esx1-secretion, and cell-wall adhesins explain the appearance of PBFs as ribbon-like cords and SBFs as lichen-like structures. A subpopulation of cells resisting the 64 × MIC rifampicin (persisters) were detected in both biofilm subtypes, and already in one-week-old SBFs. The key forces boosting their development could include subtype-dependent changes in asymmetric cell division, cell wall biogenesis, tricarboxylic acid/glyoxylate cycle activities, and energy/redox/iron metabolisms. The effect of varying ambient oxygen tensions on each cell type and non-classical protein secretion are likely factors explaining majority of the subtype-specific changes. The proteomic findings also imply that Esx1-type protein secretion is more efficient in PL and PBF cells, while SBF may prefer both the Esx5- and non-classical pathways to control virulence and prolonged viability/persistence. In conclusion, this study reports a first proteomic insight into aging mycobacterial biofilm-ECMs and indicates biofilm subtype-dependent mechanisms conferring increased adaptive potential and virulence on non-tuberculous mycobacteria.IMPORTANCEMycobacteria are naturally resilient and mycobacterial infections are notoriously difficult to treat with antibiotics, with biofilm formation being the main factor complicating the successful treatment of TB. The present study shows that non-tuberculous Mycobacterium marinum ATCC927 forms submerged- and pellicle-type biofilms with lichen- and ribbon-like structures, respectively, as well as persister cells under the same conditions. We show that both biofilm subtypes differ in terms of virulence-, tolerance- and persistence-conferring activities, highlighting the fact that both subtypes should be targeted to maximize the power of antimycobacterial treatment therapies.

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“…Mycobacterial surface proteins play an important role in guiding bacterial-host interactions (for an overview please refer to the following reviews on the topic [55][56][57]). Among these, FnBPs support mycobacterial adhesion to the respiratory mucosa via the extracellular matrix protein Fn, an interaction that is highly conserved in mycobacteria [58].…”

Section: Discussionmentioning

confidence: 99%

Mechanical Forces between Mycobacterial Antigen 85 Complex and Fibronectin

Viljoen

Alsteens

Dufrêne

2020

Cells

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Adhesion to extracellular matrix proteins is an important first step in host invasion, employed by many bacterial pathogens. In mycobacteria, the secreted Ag85 complex proteins, involved in the synthesis of the cell envelope, are known to bind to fibronectin (Fn) through molecular forces that are currently unknown. In this study, single-molecule force spectroscopy is used to study the strength, kinetics and thermodynamics of the Ag85-Fn interaction, focusing on the multidrug-resistant Mycobacterium abscessus species. Single Ag85 proteins bind Fn with a strength of~75 pN under moderate tensile loading, which compares well with the forces reported for other Fn-binding proteins. The binding specificity is demonstrated by using free Ag85 and Fn peptides with active binding sequences. The Ag85-Fn rupture force increases with mechanical stress (i.e., loading rate) according to the Friddle-Noy-de Yoreo theory. From this model, we extract thermodynamic parameters that are in good agreement with previous affinity determinations by surface plasmon resonance. Strong bonds (up to~500 pN) are observed under high tensile loading, which may favor strong mycobacterial attachment in the lung where cells are exposed to high shear stress or during hematogenous spread which leads to a disseminated infection. Our results provide new insight into the pleiotropic functions of an important mycobacterial virulence factor that acts as a stress-sensitive adhesin.

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The cell surface adhesins of Mycobacterium tuberculosis

Cited by 31 publications

References 100 publications

Surface-Shaving Proteomics of Mycobacterium marinum Identifies Biofilm Subtype-Specific Changes Affecting Virulence, Tolerance, and Persistence

Surface-Shaving Proteomics of Mycobacterium marinum Identifies Biofilm Subtype-Specific Changes Affecting Virulence, Tolerance, and Persistence

Surface-Shaving Proteomics ofMycobacterium marinumIdentifies Biofilm Subtype-Specific Changes Affecting Virulence, Tolerance and Persistence

Mechanical Forces between Mycobacterial Antigen 85 Complex and Fibronectin

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