Biomaterial Database

A membrane-depolarizing toxin substrate of the Staphylococcus aureus type VII secretion system mediates intraspecies competition. 2020

Fatima R Ulhuq, and Margarida C Gomes, and Gina M Duggan, and Manman Guo, and Chriselle Mendonca, and Grant Buchanan, and James D Chalmers, and Zhenping Cao, and Holger Kneuper, and Sarah Murdoch, and Sarah Thomson, and Henrik Strahl, and Matthias Trost, and Serge Mostowy, and Tracy Palmer

Centre for Bacterial Cell Biology, Newcastle University Biosciences Institute, Newcastle University, NE2 4HH Newcastle upon Tyne, United Kingdom.

The 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 coproduction 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 homologs at the tspA locus, suggestive of additional roles in intraspecies 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 homologs.

UI	MeSH Term	Description	Entries
D008565	Membrane Proteins	Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.	Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
D002462	Cell Membrane	The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.	Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D005810	Multigene Family	A set of genes descended by duplication and variation from some ancestral gene. Such genes may be clustered together on the same chromosome or dispersed on different chromosomes. Examples of multigene families include those that encode the hemoglobins, immunoglobulins, histocompatibility antigens, actins, tubulins, keratins, collagens, heat shock proteins, salivary glue proteins, chorion proteins, cuticle proteins, yolk proteins, and phaseolins, as well as histones, ribosomal RNA, and transfer RNA genes. The latter three are examples of reiterated genes, where hundreds of identical genes are present in a tandem array. (King & Stanfield, A Dictionary of Genetics, 4th ed)	Gene Clusters,Genes, Reiterated,Cluster, Gene,Clusters, Gene,Families, Multigene,Family, Multigene,Gene Cluster,Gene, Reiterated,Multigene Families,Reiterated Gene,Reiterated Genes
D000069377	Type VII Secretion Systems	Bacterial secretion systems found in bacteria that have a MYCOLIC ACID-containing outer membrane such as MYCOBACTERIACEAE; Corynebacteriaceae; and NOCARDIACEAE. These are also known as ESX secretion systems because the first to be discovered is involved in secreting major virulence factors EsxA and EsxB. There are several subtypes of T7SSs including ESX-1, ESX-2, ESX-3, ESX-4, and ESX-5 secretion systems. The subtypes share some core components including an inner membrane channel-forming ATPase complex, a membrane-anchored mycosin, and a second channel that spans the outer mycolic acid-containing membrane.	ESX Secretion System,Type 7 Secretion System,Type VII Secretion System,ESX Secretion Systems,Secretion Systems, ESX,Secretion Systems, Type 7,Secretion Systems, Type VII,T7SS Secretion System,Type 7 Secretion Systems,Secretion System, ESX,Secretion System, T7SS,System, ESX Secretion,System, T7SS Secretion,Systems, ESX Secretion
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000942	Antigens, Bacterial	Substances elaborated by bacteria that have antigenic activity.	Bacterial Antigen,Bacterial Antigens,Antigen, Bacterial
D001426	Bacterial Proteins	Proteins found in any species of bacterium.	Bacterial Gene Products,Bacterial Gene Proteins,Gene Products, Bacterial,Bacterial Gene Product,Bacterial Gene Protein,Bacterial Protein,Gene Product, Bacterial,Gene Protein, Bacterial,Gene Proteins, Bacterial,Protein, Bacterial,Proteins, Bacterial
D013203	Staphylococcal Infections	Infections with bacteria of the genus STAPHYLOCOCCUS.	Infections, Staphylococcal,Staphylococcus aureus Infection,Staphylococcal Infection,Staphylococcus aureus Infections
D013211	Staphylococcus aureus	Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications.
D014118	Toxins, Biological	Specific, characterizable, poisonous chemicals, often PROTEINS, with specific biological properties, including immunogenicity, produced by microbes, higher plants (PLANTS, TOXIC), or ANIMALS.	Biological Toxins