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.

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 The Ess/Type VII secretion system of Staphylococcus aureus shows unexpected genetic diversity

BMC Genomics ◽  
2016 ◽  
Vol 17 (1) ◽  
Author(s):  
Ben Warne ◽  
Catriona P. Harkins ◽  
Simon R. Harris ◽  
Alexandra Vatsiou ◽  
Nicola Stanley-Wall ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Staphylococcus Aureus ◽  
Secretion System ◽  
Type Vii Secretion ◽  
Type Vii Secretion System

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 Flotillin scaffold activity contributes to type VII secretion system assembly in Staphylococcus aureus

2017 ◽  
Vol 13 (11) ◽  
pp. e1006728 ◽  
Author(s):  
Benjamin Mielich-Süss ◽  
Rabea M. Wagner ◽  
Nicole Mietrach ◽  
Tobias Hertlein ◽  
Gabriella Marincola ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Secretion System ◽  
Type Vii Secretion ◽  
Type Vii Secretion System

scholarly journals Heme-iron plays a key role in the regulation of the Ess/Type VII secretion system ofStaphylococcus aureusRN6390

2017 ◽  
Author(s):  
M. Guillermina Casabona ◽  
Holger Kneuper ◽  
Daniela Alferes de Lima ◽  
Catriona P. Harkins ◽  
Martin Zoltner ◽  
...  
Keyword(s):  
Iron Homeostasis ◽  
Iron Acquisition ◽  
Secretion System ◽  
Heme Iron ◽  
Species Competition ◽  
Transcript Analysis ◽  
Type Vii Secretion ◽  
Protein Secretion System ◽  
Type Vii Secretion System ◽  
Translational Level

ABSTRACTTheStaphylococcus aureusType VII protein secretion system (T7SS) plays important roles in virulence and intra-species competition. Here we show that the T7SS in strain RN6390 is activated by supplementing the growth medium with hemoglobin, and its cofactor hemin (heme B). Transcript analysis and secretion assays suggest that activation by hemin occurs at a transcriptional and a post-translational level. Loss of T7 secretion activity by deletion ofessCresults in upregulation of genes required for iron acquisition. Taken together these findings suggest that the T7SS plays a role in iron homeostasis in at least someS. aureusstrains.

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.

scholarly journals The type VII secretion system protects Staphylococcus aureus against antimicrobial host fatty acids

2019 ◽  
Author(s):  
Arnaud Kengmo Tchoupa ◽  
Kate E. Watkins ◽  
Rebekah A. Jones ◽  
Agnès Kuroki ◽  
Mohammad Tauqeer Alam ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Staphylococcus Aureus ◽  
Cell Membrane ◽  
Mutant Cell ◽  
Membrane Damage ◽  
Membrane Integrity ◽  
Secretion System ◽  
Membrane Phospholipids ◽  
Type Vii Secretion ◽  
Type Vii Secretion System

SummaryThe Staphylococcus aureus type VII secretion system (T7SS) exports several proteins that are pivotal for bacterial virulence. The mechanisms underlying T7SS-mediated staphylococcal survival during infection nevertheless remain unclear. Here we show that the absence of EsxC, a small secreted effector implicated in bacterial persistence, results in cell membrane defects in S. aureus. Interestingly, isogenic mutants lacking EsxC, other T7SS effectors EsxA and EsxB, or the membrane-bound ATPase EssC, are more sensitive to killing by the host-derived antimicrobial fatty acid, linoleic acid (LA), compared to the wild-type (WT). LA induces more cell membrane damage in the T7SS mutants compared to the WT. Although WT and mutant strains did not differ in their ability to bind labelled LA, membrane lipid profiles show that T7SS mutants are less able to incorporate LA into their membrane phospholipids. Furthermore, proteomic analyses of WT and mutant cell fractions reveal that, in addition to compromising membranes, T7SS defects induce oxidative stress and hamper their response to LA challenge. Thus, our findings indicate that T7SS is crucial for S. aureus membrane integrity and homeostasis, which is critical when bacteria encounter antimicrobial fatty acids.

scholarly journals The beneficial rhizobacterium Bacillus velezensis acquires iron from roots via a type VII secretion system for colonization

2021 ◽  
Author(s):  
Yunpeng Liu ◽  
Xia Shu ◽  
Lin Chen ◽  
Huihui Zhang ◽  
Haichao Feng ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Root Colonization ◽  
Secretion System ◽  
Root Cell ◽  
Plant Colonization ◽  
Secretion Systems ◽  
Bacillus Velezensis ◽  
Root Cells ◽  
Type Vii Secretion ◽  
Type Vii Secretion System

Niche colonization is the key for bacterial adaptation to the environment, and competition for iron largely determines root colonization by rhizosphere microbes. Pathogenic and beneficial symbiotic bacteria use various unique secretion systems to support plant colonization or acquire limited resources from the environment. However, ubiquitous nonsymbiotic beneficial rhizobacteria have never been reported to use a unique secretion system to facilitate colonization. Here, we show that the type VII secretion system (T7SS) of the beneficial rhizobacterium Bacillus velezensis SQR9 contributes to root colonization. Knocking out T7SS and the major secreted protein YukE in SQR9 caused a significant decrease in root colonization. Moreover, the T7SS and YukE caused iron loss in plant roots in the early stage after inoculation, which contributed to root colonization by SQR9. Interestingly, purified YukE, but not inactivated YukE, could change the permeability of root cells. We speculated that secreted YukE might be directly inserted into the root cell membrane to cause iron leakage, indicating that the bacterial protein and root cell membrane interact directly. Moreover, a bacterial siderophore and the T7SS may be coordinately involved in iron acquisition by B. velezensis SQR9 for efficient root colonization. We showed that the beneficial rhizobacterium B. velezensis SQR9 could acquire iron from roots via the T7SS for rapid colonization. These findings provide the first insight into the function of the unique secretion system in nonsymbiotic beneficial rhizobacteria and reveal a novel mutualism in which plants and bacteria might share iron in a sequential manner.

scholarly journals A membrane-depolarizing toxin substrate of the Staphylococcus aureus Type VII secretion system mediates intra-species competition

2018 ◽  
Author(s):  
Fatima R. Ulhuq ◽  
Margarida C. Gomes ◽  
Gina Duggan ◽  
Manman Guo ◽  
Chriselle Mendonca ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Pathogenic Bacteria ◽  
Secretion System ◽  
Mucosal Barrier ◽  
Infection Model ◽  
Species Competition ◽  
Type Vii Secretion ◽  
Proteomic Approach ◽  
Type Vii Secretion System

AbstractThe type VII protein secretion system (T7SS) is conserved across Staphylococcus aureus strains and plays important roles in virulence and interbacterial competition. To date only one T7SS substrate protein, encoded in a subset of S. aureus genomes, has been functionally characterized. Here, using an unbiased proteomic approach, we identify TspA as a further T7SS substrate. TspA is encoded distantly from the T7SS gene cluster and is found across all S. aureus strains as well as in Listeria and Enterococci. Heterologous expression of TspA from S. aureus strain RN6390 indicates its C-terminal domain is toxic when targeted to the Escherichia coli periplasm and that it depolarizes the cytoplasmic membrane. The membrane depolarizing activity is alleviated by co-production of the membrane-bound TsaI immunity protein, which is encoded adjacent to tspA on the S. aureus chromosome. Using a zebrafish hindbrain ventricle infection model, we demonstrate that the T7SS of strain RN6390 promotes bacterial replication in vivo, and deletion of tspA leads to increased bacterial clearance. The toxin domain of TspA is highly polymorphic and S. aureus strains encode multiple tsaI homologues at the tspA locus, suggestive of additional roles in intra-species competition. In agreement, we demonstrate TspA-dependent growth inhibition of RN6390 by strain COL in the zebrafish infection model that is alleviated by the presence of TsaI homologues.Significance statementStaphylococcus aureus, a human commensal organism that asymptomatically colonizes the nares, is capable of causing serious disease following breach of the mucosal barrier. S. aureus strains encode a Type VII secretion system (T7SS) that is required for virulence in mouse infection models, and some strains also secrete a nuclease toxin by this route that has antibacterial activity. Here we identify TspA, widely found in Staphylococci and other pathogenic bacteria, as a T7 substrate. We show that TspA has membrane-depolarizing activity and that S. aureus uses TspA to inhibit the growth of a bacterial competitor in vivo.

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