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 ◽  
...  

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.

2021 ◽  
Vol 75 (1) ◽  
Author(s):  
Lisa Bowman ◽  
Tracy Palmer

The type VII protein secretion system (T7SS) of Staphylococcus aureus is encoded at the ess locus. T7 substrate recognition and protein transport are mediated by EssC, a membrane-bound multidomain ATPase. Four EssC sequence variants have been identified across S. aureus strains, each accompanied by a specific suite of substrate proteins. The ess genes are upregulated during persistent infection, and the secretion system contributes to virulence in disease models. It also plays a key role in intraspecies competition, secreting nuclease and membrane-depolarizing toxins that inhibit the growth of strains lacking neutralizing immunity proteins. A genomic survey indicates that the T7SS is widely conserved across staphylococci and is encoded in clusters that contain diverse arrays of toxin and immunity genes. The presence of genomic islands encoding multiple immunity proteins in species such as Staphylococcus warneri that lack the T7SS points to a major role for the secretion system in bacterial antagonism. Expected final online publication date for the Annual Review of Microbiology, Volume 75 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.


2017 ◽  
Author(s):  
M. Guillermina Casabona ◽  
Grant Buchanan ◽  
Martin Zoltner ◽  
Catriona P. Harkins ◽  
Matthew T.G. Holden ◽  
...  

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.


2018 ◽  
Author(s):  
Fatima R. Ulhuq ◽  
Margarida C. Gomes ◽  
Gina Duggan ◽  
Manman Guo ◽  
Chriselle Mendonca ◽  
...  

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.


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

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

BMC Genomics ◽  
2016 ◽  
Vol 17 (1) ◽  
Author(s):  
Ben Warne ◽  
Catriona P. Harkins ◽  
Simon R. Harris ◽  
Alexandra Vatsiou ◽  
Nicola Stanley-Wall ◽  
...  

2015 ◽  
Vol 83 (11) ◽  
pp. 4349-4361 ◽  
Author(s):  
Swati Shah ◽  
Joe R. Cannon ◽  
Catherine Fenselau ◽  
Volker Briken

ABSTRACTThe ESX-5 secretion system ofMycobacterium tuberculosisis important for bacterial virulence and for the secretion of the large PE/PPE protein family, whose genes constitute 10% of theM. tuberculosisgenome. A four-gene region of the ESX-5 system is duplicated three times in theM. tuberculosisgenome, but the functions of these duplicates are unknown. Here we investigated one of these duplicates: the region carrying theesxI,esxJ,ppe15, andpe8genes (ESX-5a). An ESX-5a deletion mutant in the model systemM. marinumbackground was deficient in the secretion of some members of the PE/PPE family of proteins. Surprisingly, we also identified other proteins that are not members of this family, thus expanding the range of ESX-5 secretion substrates. In addition, we demonstrated that ESX-5a is important for the virulence ofM. marinumin the zebrafish model. Furthermore, we showed the role of theM. tuberculosisESX-5a region in inflammasome activation but not host cell death induction, which is different from the case for theM. tuberculosisESX-5 system. In conclusion, the ESX-5a region is nonredundant with its ESX-5 paralog and is necessary for secretion of a specific subset of proteins inM. tuberculosisandM. marinumthat are important for bacterial virulence ofM. marinum. Our findings point to a role for the three ESX-5 duplicate regions in the selection of substrates for secretion via ESX-5, and hence, they provide the basis for a refined model of the molecular mechanism of this type VII secretion system.


iScience ◽  
2021 ◽  
pp. 103585
Author(s):  
Yuchen Wang ◽  
Yuting Tang ◽  
Chen Lin ◽  
Junli Zhang ◽  
Juntao Mai ◽  
...  

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