Dynamic Remodeling of the Host Cell Membrane by Virulent Mycobacterial Sulfoglycolipid-1

Mishra, Manjari; Adhyapak, Pranav; Dadhich, Ruchika; Kapoor, Shobhna

doi:10.1038/s41598-019-49343-2

Cited by 32 publications

(47 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Aside from interactions with specific surface receptors on human macrophages, it remains unknown whether SLs can influence the dynamics of host cell membranes since SLs are located at the host-bacterium interface. It was recently found that SL-I mediates the remodeling of THP-1 cell membranes in a time and concentration-dependent manner that resulted in increased host membrane fluidity and altered membrane-associated signaling [47]. This evidence supports the finding that SLs inhibit the formation of TLR2/TLR1 and TLR2/TLR6 heterodimers in the host cell membrane [46].…”

Section: Sulfolipids (Sls)supporting

confidence: 71%

Mycobacterial Virulence Factors: Surface-Exposed Lipids and Secreted Proteins

Liu

2020

IJMS

View full text Add to dashboard Cite

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.

show abstract

Section: Sulfolipids (Sls)supporting

confidence: 71%

Mycobacterial Virulence Factors: Surface-Exposed Lipids and Secreted Proteins

Liu

2020

IJMS

View full text Add to dashboard Cite

show abstract

“…Changes in membrane lipid composition and organization are generally thought to influence many cellular functions. Our findings go beyond the functional observations that Mtb uses envelope lipids to remodel the host membrane and divert macrophages functions (Laneelle and Tocanne, 1980;Sut et al, 1990;Welin et al, 2008;Augenstreich et al, 2019;Mishra et al, 2019). They provide evidence that insertion of lipids into host cell membranes helps the bacteria exploit membrane partners that direct the cell's responses.…”

Section: Discussionmentioning

confidence: 49%

Phthiocerol Dimycocerosates From Mycobacterium tuberculosis Increase the Membrane Activity of Bacterial Effectors and Host Receptors

Augenstreich

Haanappel

Sayes

et al. 2020

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Mycobacterium tuberculosis (Mtb) synthesizes a variety of atypical lipids that are exposed at the cell surface and help the bacterium infect macrophages and escape elimination by the cell's immune responses. In the present study, we investigate the mechanism of action of one family of hydrophobic lipids, the phthiocerol dimycocerosates (DIM/PDIM), major lipid virulence factors. DIM are transferred from the envelope of Mtb to host membranes during infection. Using the polarity-sensitive fluorophore C-Laurdan, we visualized that DIM decrease the membrane polarity of a supported lipid bilayer put in contact with mycobacteria, even beyond the site of contact. We observed that DIM activate the complement receptor 3, a predominant receptor for phagocytosis of Mtb by macrophages. DIM also increased the activity of membrane-permeabilizing effectors of Mtb, among which the virulence factor EsxA. This is consistent with previous observations that DIM help Mtb disrupt host cell membranes. Taken together, our data show that transferred DIM spread within the target membrane, modify its physical properties and increase the activity of host cell receptors and bacterial effectors, diverting in a non-specific manner host cell functions. We therefore bring new insight into the molecular mechanisms by which DIM increase Mtb's capability to escape the cell's immune responses.

show abstract

“…Whether DIMs promote the targeting of Mtb through autophagy machinery also remains to be investigated [26]. Another work has reported that purified Mtb SLs promote GFP-LC3 puncta accumulation in macrophages [27]. Again, it is unclear whether SLs activate autophagy or prevent LC3 turnover.…”

Section: Introductionmentioning

confidence: 99%

The Lipid Virulence Factors of Mycobacterium tuberculosis Exert Multilayered Control over Autophagy-Related Pathways in Infected Human Macrophages

Bah

Sanicas

Nigou

et al. 2020

Cells

View full text Add to dashboard Cite

Autophagy is an important innate immune defense mechanism that controls Mycobacterium tuberculosis (Mtb) growth inside macrophages. Autophagy machinery targets Mtb-containing phagosomes via xenophagy after damage to the phagosomal membrane due to the Type VII secretion system Esx-1 or via LC3-associated phagocytosis without phagosomal damage. Conversely, Mtb restricts autophagy-related pathways via the production of various bacterial protein factors. Although bacterial lipids are known to play strategic functions in Mtb pathogenesis, their role in autophagy manipulation remains largely unexplored. Here, we report that the lipid virulence factors sulfoglycolipids (SLs) and phthiocerol dimycocerosates (DIMs) control autophagy-related pathways through distinct mechanisms in human macrophages. Using knock-out and knock-in mutants of Mtb and Mycobacterium bovis BCG (Bacille Calmette Guerin) and purified lipids, we found that (i) Mtb mutants with DIM and SL deficiencies promoted functional autophagy via an MyD88-dependent and phagosomal damage-independent pathway in human macrophages; (ii) SLs limited this pathway by acting as TLR2 antagonists; (iii) DIMs prevented phagosomal damage-independent autophagy while promoting Esx-1-dependent xenophagy; (iv) and DIMs, but not SLs, limited the acidification of LC3-positive Mtb compartments. In total, our study reveals an unexpected and intricate role for Mtb lipid virulence factors in controlling autophagy-related pathways in human macrophages, thus providing further insight into the autophagy manipulation tactics deployed by intracellular bacterial pathogens.

show abstract

Dynamic Remodeling of the Host Cell Membrane by Virulent Mycobacterial Sulfoglycolipid-1

Cited by 32 publications

References 49 publications

Mycobacterial Virulence Factors: Surface-Exposed Lipids and Secreted Proteins

Mycobacterial Virulence Factors: Surface-Exposed Lipids and Secreted Proteins

Phthiocerol Dimycocerosates From Mycobacterium tuberculosis Increase the Membrane Activity of Bacterial Effectors and Host Receptors

The Lipid Virulence Factors of Mycobacterium tuberculosis Exert Multilayered Control over Autophagy-Related Pathways in Infected Human Macrophages

Contact Info

Product

Resources

About