scholarly journals Crystallographic observation of the movement of the membrane-distal domain of the T7SS core component EccB1 fromMycobacterium tuberculosis

2016 ◽  
Vol 72 (2) ◽  
pp. 139-144
Author(s):  
Xiao-Qian Xie ◽  
Xiao-Li Zhang ◽  
Chao Qi ◽  
De-Feng Li ◽  
Joy Fleming ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Atpase Activity ◽  
Virulence Factors ◽  
Conformational Changes ◽  
Secretion System ◽  
Secretion Systems ◽  
Core Component ◽  
Substrate Transport ◽  
Type Vii Secretion ◽  
Type Vii Secretion System

The protein EccB1, a core component of the type VII secretion system (T7SS) ofMycobacterium tuberculosis, has been identified as an ATPase and is essential for the secretion of virulence factors by the ESX-1 system. In a previous study, EccB1 structures were determined in two different conformations. Here, two new conformations are identified and described. These four conformations present snapshots of the swinging movement of the membrane-distal domain A2. The movement of this domain involves conformational changes in two flexible loops (loop A, residues 243–264, and loop B, residues 324–341) which are rich in proline and glycine residues and connect domain A2 to domains C1 and B2. It is proposed that the movement of this domain is related to the ATPase activity of EccB1 and its homologues, as well as to the substrate transport of ESX secretion systems.

scholarly journals EsaB is a core component of the Staphylococcus aureus Type VII secretion system

2017 ◽  
Author(s):  
M. Guillermina Casabona ◽  
Grant Buchanan ◽  
Martin Zoltner ◽  
Catriona P. Harkins ◽  
Matthew T.G. Holden ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Fluorescent Protein ◽  
Iron Acquisition ◽  
Yellow Fluorescent Protein ◽  
Secretion System ◽  
Secretion Systems ◽  
Core Component ◽  
Type Vii Secretion ◽  
Bacterial Competition ◽  
Type Vii Secretion System

AbstractType VII secretion systems (T7SS) are found in many bacteria and secrete proteins involved in virulence and bacterial competition. In Staphylococcus aureus the small ubiquitin-like EsaB protein has been previously implicated as having a regulatory role in the production of the EsxC substrate. Here we show that in the S. aureus RN6390 strain, EsaB does not genetically regulate production of any T7 substrates or components, but is indispensable for secretion activity. Consistent with EsaB being a core component of the T7SS, loss of either EsaB or EssC are associated with upregulation of a common set of iron acquisition genes. However, a further subset of genes were dysregulated only in the absence of EsaB. In addition, fractionation revealed that although an EsaB fusion to yellow fluorescent protein partially localised to the membrane, it was still membrane-localised when the T7SS was absent. Taken together our findings suggest that EsaB has T7SS-dependent and T7SS-independent roles in S. aureus.

Core component EccB1 of the Mycobacterium tuberculosis type VII secretion system is a periplasmic ATPase

2015 ◽  
Vol 29 (12) ◽  
pp. 4804-4814 ◽  
Author(s):  
Xiao‐Li Zhang ◽  
De‐Feng Li ◽  
Joy Fleming ◽  
Li‐Wei Wang ◽  
Ying Zhou ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Secretion System ◽  
Core Component ◽  
Type Vii Secretion ◽  
Type Vii Secretion System

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

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 666 ◽  
Author(s):  
Aïcha Bah ◽  
Merlin Sanicas ◽  
Jérôme Nigou ◽  
Christophe Guilhot ◽  
Catherine Astarie-Dequeker ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Virulence Factors ◽  
Defense Mechanism ◽  
Immune Defense ◽  
Knock Out ◽  
Human Macrophages ◽  
Type Vii Secretion ◽  
Type Vii Secretion System ◽  
Phagosomal Membrane ◽  
Phthiocerol Dimycocerosates

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.

scholarly journals A type VII secretion system of Streptococcus gallolyticus subsp. gallolyticus contributes to gut colonization and the development of colon tumors

2021 ◽  
Vol 17 (1) ◽  
pp. e1009182
Author(s):  
John Culver Taylor ◽  
Xinsheng Gao ◽  
Juan Xu ◽  
Michael Holder ◽  
Joseph Petrosino ◽  
...  
Keyword(s):  
Bacterial Culture ◽  
Secretion System ◽  
Host Cells ◽  
Secretion Systems ◽  
Colon Tumors ◽  
Type Vii Secretion ◽  
Streptococcus Gallolyticus ◽  
Gut Colonization ◽  
Type Vii Secretion System

Streptococcus gallolyticus subspecies gallolyticus (Sgg) has a strong clinical association with colorectal cancer (CRC) and actively promotes the development of colon tumors. However, the molecular determinants involved in Sgg pathogenicity in the gut are unknown. Bacterial type VII secretion systems (T7SS) mediate pathogen interactions with their host and are important for virulence in pathogenic mycobacteria and Staphylococcus aureus. Through genome analysis, we identified a locus in Sgg strain TX20005 that encodes a putative type VII secretion system (designated as SggT7SST05). We showed that core genes within the SggT7SST05 locus are expressed in vitro and in the colon of mice. Western blot analysis showed that SggEsxA, a protein predicted to be a T7SS secretion substrate, is detected in the bacterial culture supernatant, indicating that this SggT7SST05 is functional. Deletion of SggT7SST05 (TX20005Δesx) resulted in impaired bacterial adherence to HT29 cells and abolished the ability of Sgg to stimulate HT29 cell proliferation. Analysis of bacterial culture supernatants suggest that SggT7SST05-secreted factors are responsible for the pro-proliferative activity of Sgg, whereas Sgg adherence to host cells requires both SggT7SST05-secreted and bacterial surface-associated factors. In a murine gut colonization model, TX20005Δesx showed significantly reduced colonization compared to the parent strain. Furthermore, in a mouse model of CRC, mice exposed to TX20005 had a significantly higher tumor burden compared to saline-treated mice, whereas those exposed to TX20005Δesx did not. Examination of the Sgg load in the colon in the CRC model suggests that SggT7SST05-mediated activities are directly involved in the promotion of colon tumors. Taken together, these results reveal SggT7SST05 as a previously unrecognized pathogenicity determinant for Sgg colonization of the colon and promotion of colon tumors.

scholarly journals The Whole-Genome Sequence of Plasmid-Bearing Staphylococcus argenteus Strain B3-25B from Retail Beef Liver Encodes the Type VII Secretion System and Several Virulence Factors

2019 ◽  
Vol 8 (45) ◽  
Author(s):  
Leena Neyaz ◽  
Anand B. Karki ◽  
Mohamed K. Fakhr
Keyword(s):  
Virulence Factors ◽  
Genome Sequence ◽  
Secretion System ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Circular Chromosome ◽  
Beef Liver ◽  
Content Type ◽  
Type Vii Secretion ◽  
Type Vii Secretion System

The whole-genome sequence of Staphylococcus argenteus strain B3-25B, isolated from retail beef liver, comprises a circular chromosome (2,676,222 bp) and a single plasmid (21,570 bp). The chromosome harbors genes encoding the type VII secretion system and several virulence factors.

scholarly journals Structure and dynamics of the ESX-5 type VII secretion system of Mycobacterium tuberculosis

2020 ◽  
Author(s):  
Catalin M. Bunduc ◽  
Dirk Fahrenkamp ◽  
Jiri Wald ◽  
Roy Ummels ◽  
Wilbert Bitter ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Protein Transport ◽  
Cell Envelope ◽  
Transmembrane Helix ◽  
Transport Systems ◽  
Secretion Systems ◽  
Type Vii Secretion ◽  
Membrane Complex ◽  
Type Vii Secretion System ◽  
Inner Membrane Complex

AbstractMycobacterium tuberculosis causes one of the most important infectious diseases in humans, leading to 1.5 million deaths every year. Specialized protein transport systems, called type VII secretion systems (T7SSs), are central for its virulence, but also crucial for nutrient and metabolite transport across the mycobacterial cell envelope. Here we present the first structure of an intact T7SS inner membrane complex of M. tuberculosis. We show how the 2.32 MDa, 165 transmembrane helices-containing ESX-5 assembly is restructured and stabilized as a trimer of dimers by the MycP5 protease. A trimer of MycP5 caps a central periplasmic dome-like chamber formed by three EccB5 dimers, with the proteolytic sites facing towards the cavity. This chamber suggests a central secretion and processing conduit. Complexes without MycP5 show disruption of the EccB5 periplasmic assembly and increased flexibility, highlighting the importance of this component for complex integrity. Beneath the EccB5-MycP5 chamber, dimers of the EccC5 ATPase assemble into three four-transmembrane helix bundles, which together seal the potential central secretion channel. Individual cytoplasmic EccC5 domains adopt two distinctive conformations, likely reflecting different secretion states. Our work suggests a novel mechanism of protein transport and provides a structural scaffold to aid drug development against the major human pathogen.

scholarly journals ESX secretion system: The gatekeepers of mycobacterial survivability and pathogenesis

2020 ◽  
Author(s):  
Sadhana Roy ◽  
Debika Ghatak ◽  
Payel Das ◽  
Somdeb BoseDasgupta
Keyword(s):  
Metal Ion ◽  
Current Knowledge ◽  
Ion Homeostasis ◽  
Secretion System ◽  
Special Focus ◽  
Host Immune System ◽  
Secretion Systems ◽  
Metal Ion Homeostasis ◽  
Type Vii Secretion ◽  
Type Vii Secretion System

AbstractMycobacterium tuberculosis, the causative agent of Tuberculosis has plagued humankind for ages and has surfaced stronger than ever with the advent of drug resistance. Mycobacteria are adept at evading the host immune system and establishing infection by engaging host factors and secreting several virulence factors. Hence these secretion systems play a key role in mycobacterial pathogenesis. The type VII secretion system or ESX (early secretory antigenic target (ESAT6) secretion) system is one such crucial system that comprises five different pathways having distinct roles in mycobacterial proliferation, pathogenesis, cytosolic escape within macrophages, regulation of macrophage apoptosis, metal ion homeostasis, etc. ESX 1–5 systems are implicated in the secretion of a plethora of proteins, of which only a few are functionally characterized. Here we summarize the current knowledge of ESX secretion systems of mycobacteria with a special focus on ESX-1 and ESX-5 systems that subvert macrophage defenses and help mycobacteria to establish their niche within the macrophage.

scholarly journals Structure of the mycobacterial ESX-5 type VII secretion system pore complex

2021 ◽  
Vol 7 (26) ◽  
pp. eabg9923
Author(s):  
Katherine S. H. Beckham ◽  
Christina Ritter ◽  
Grzegorz Chojnowski ◽  
Daniel S. Ziemianowicz ◽  
Edukondalu Mullapudi ◽  
...  
Keyword(s):  
Fundamental Principle ◽  
Secretion System ◽  
Dynamic State ◽  
Secretion Systems ◽  
Type Vii Secretion ◽  
High Resolution Structure ◽  
Conformational Plasticity ◽  
Type Vii Secretion System ◽  
Membrane Spanning ◽  
Bacterial Secretion

The ESX-5 type VII secretion system is a membrane-spanning protein complex key to the virulence of mycobacterial pathogens. However, the overall architecture of the fully assembled translocation machinery and the composition of the central secretion pore have remained unknown. Here, we present the high-resolution structure of the 2.1-megadalton ESX-5 core complex. Our structure captured a dynamic, secretion-competent conformation of the pore within a well-defined transmembrane section, sandwiched between two flexible protein layers at the cytosolic entrance and the periplasmic exit. We propose that this flexibility endows the ESX-5 machinery with large conformational plasticity required to accommodate targeted protein secretion. Compared to known secretion systems, a highly dynamic state of the pore may represent a fundamental principle of bacterial secretion machineries.

Sign in / Sign up

Export Citation Format

Share Document