scholarly journals Infect and Inject: How Mycobacterium tuberculosis Exploits Its Major Virulence-Associated Type VII Secretion System, ESX-1

2019 ◽  
pp. 113-126 ◽  
Author(s):  
Sangeeta Tiwari ◽  
Rosalyn Casey ◽  
Celia W. Goulding ◽  
Suzie Hingley-Wilson ◽  
William R. Jacobs
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Secretion System ◽  
Type Vii Secretion ◽  
Type Vii Secretion System

scholarly journals A heterodimer of EsxA and EsxB is involved in sporulation and is secreted by a type VII secretion system in Streptomyces coelicolor

Microbiology ◽  
2010 ◽  
Vol 156 (6) ◽  
pp. 1719-1729 ◽  
Author(s):  
Sandra Akpe San Roman ◽  
Paul D. Facey ◽  
Lorena Fernandez-Martinez ◽  
Caridad Rodriguez ◽  
Carlos Vallin ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Streptomyces Coelicolor ◽  
Regulatory Gene ◽  
Secretion System ◽  
Model Species ◽  
Type Vii Secretion ◽  
Expression Of Genes ◽  
Dna Contents ◽  
Aerial Hyphae ◽  
Type Vii Secretion System

An esx locus, related to the multiple esx loci of Mycobacterium tuberculosis, is conserved in all sequenced Streptomyces genomes, where it is associated with the developmental regulatory gene bldB. Here we demonstrate that the esxBA operon, comprising part of the locus, has a novel morphogenetic function in the model species Streptomyces coelicolor. This operon encodes two proteins belonging to the WXG-100 superfamily that can form a heterodimer and are secreted in the absence of signal sequences. A mutation in esxBA results in a delay in sporulation, with eventual development of aerial hyphae with chains of abnormally sized spore compartments possessing irregular DNA contents. During early sporulation, expression of the operon is elevated in a bldB mutant. Other genes in the locus, notably SCO5734 and SCO5721, encode components of a type VII secretion system. Disruption of either of these genes prevents secretion of EsxAB but has no effect on sporulation. To explain the morphogenetic function of EsxAB, we propose that the heterodimer sequesters a regulator of expression of genes involved in nucleoid organization during sporulation.

scholarly journals Mycobacterium tuberculosis cording in the cytosol of live lymphatic endothelial cells

2019 ◽  
Author(s):  
Thomas R. Lerner ◽  
Christophe J. Queval ◽  
Rachel P. Lai ◽  
Matthew Russell ◽  
Antony Fearns ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mycobacterium Tuberculosis ◽  
Secretion System ◽  
Lymphatic Endothelial Cells ◽  
Rna Seq ◽  
Size Dependent ◽  
Type Vii Secretion ◽  
Type Vii Secretion System ◽  
Dependent Mechanism

AbstractThe ability of Mycobacterium tuberculosis to form serpentine cords is intrinsically related to its virulence, but specifically how M. tuberculosis cording contributes to pathogenesis remains obscure. We show that several M. tuberculosis clinical isolates form intracellular cords in primary human lymphatic endothelial cells (hLEC) in vitro and also in the lymph nodes of patients with tuberculosis. We identified via RNA-seq a transcriptional programme in hLEC that activates cellular pro-survival and cytosolic surveillance of intracellular pathogens pathways. Consistent with this, cytosolic access of hLEC is required for intracellular M. tuberculosis cording; and cord formation is dependent on the M. tuberculosis ESX-1 type VII secretion system and the mycobacterial lipid PDIM. Finally, we show that M. tuberculosis cording is a novel size-dependent mechanism used by the pathogen to evade xenophagy in the cytosol of endothelial cells. These results provide a mechanism that explains the long-standing association between M. tuberculosis cording and virulence.

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 ESX-1-Independent Horizontal Gene Transfer by Mycobacterium tuberculosis Complex Strains

mBio ◽  
2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Jan Madacki ◽  
Mickael Orgeur ◽  
Guillem Mas Fiol ◽  
Wafa Frigui ◽  
Laurence Ma ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mycobacterium Smegmatis ◽  
Secretion System ◽  
Dna Transfer ◽  
Chromosomal Dna ◽  
Content Type ◽  
Type Vii Secretion ◽  
Wide Range ◽  
Population Structures ◽  
Type Vii Secretion System

ABSTRACT Current models of horizontal gene transfer (HGT) in mycobacteria are based on “distributive conjugal transfer” (DCT), an HGT type described in the fast-growing, saprophytic model organism Mycobacterium smegmatis, which creates genome mosaicism in resulting strains and depends on an ESX-1 type VII secretion system. In contrast, only few data on interstrain DNA transfer are available for tuberculosis-causing mycobacteria, for which chromosomal DNA transfer between two Mycobacterium canettii strains was reported, a process which, however, was not observed for Mycobacterium tuberculosis strains. Here, we have studied a wide range of human- and animal-adapted members of the Mycobacterium tuberculosis complex (MTBC) using an optimized filter-based mating assay together with three selected strains of M. canettii that acted as DNA recipients. Unlike in previous approaches, we obtained a high yield of thousands of recombinants containing transferred chromosomal DNA fragments from various MTBC donor strains, as confirmed by whole-genome sequence analysis of 38 randomly selected clones. While the genome organizations of the obtained recombinants showed mosaicisms of donor DNA fragments randomly integrated into a recipient genome backbone, reminiscent of those described as being the result of ESX-1-mediated DCT in M. smegmatis, we observed similar transfer efficiencies when ESX-1-deficient donor and/or recipient mutants were used, arguing that in tubercle bacilli, HGT is an ESX-1-independent process. These findings provide new insights into the genetic events driving the pathoevolution of M. tuberculosis and radically change our perception of HGT in mycobacteria, particularly for those species that show recombinogenic population structures despite the natural absence of ESX-1 secretion systems. IMPORTANCE Data on the bacterial sex-mediated impact on mycobacterial evolution are limited. Hence, our results presented here are of importance as they clearly demonstrate the capacity of a wide range of human- and animal-adapted Mycobacterium tuberculosis complex (MTBC) strains to transfer chromosomal DNA to selected strains of Mycobacterium canettii. Most interestingly, we found that interstrain DNA transfer among tubercle bacilli was not dependent on a functional ESX-1 type VII secretion system, as ESX-1 deletion mutants of potential donor and/or recipient strains yielded numbers of recombinants similar to those of their respective parental strains. These results argue that HGT in tubercle bacilli is organized in a way different from that of the most widely studied Mycobacterium smegmatis model, a finding that is also relevant beyond tubercle bacilli, given that many mycobacteria, like, for example, Mycobacterium avium or Mycobacterium abscessus, are naturally devoid of an ESX-1 secretion system but show recombinogenic, mosaic-like genomic population structures.

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 Structure of EspB from the ESX-1 Type VII Secretion System and Insights into its Export Mechanism

Structure ◽  
2015 ◽  
Vol 23 (3) ◽  
pp. 571-583 ◽  
Author(s):  
Matthew Solomonson ◽  
Dheva Setiaputra ◽  
Karl A.T. Makepeace ◽  
Emilie Lameignere ◽  
Evgeniy V. Petrotchenko ◽  
...  
Keyword(s):  
Secretion System ◽  
Type Vii Secretion ◽  
Type Vii Secretion System

A Chimeric EccB-MycP Fusion Protein is Functional and a Stable Component of the ESX-5 Type VII Secretion System Membrane Complex

2020 ◽  
Vol 432 (4) ◽  
pp. 1265-1278 ◽  
Author(s):  
Vincent J.C. van Winden ◽  
Catalin M. Bunduc ◽  
Roy Ummels ◽  
Wilbert Bitter ◽  
Edith N.G. Houben
Keyword(s):  
Fusion Protein ◽  
Secretion System ◽  
Stable Component ◽  
Type Vii Secretion ◽  
Membrane Complex ◽  
Type Vii Secretion System
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