Microbiology: Sec and Tat Secreted Proteins in Virulence

Sec and Tat Secreted Proteins and Virulence

• Sec and Tat secreted proteins can contribute to virulence in pathogens.
• Examples of Sec secreted proteins include autolysins of Listeria monocytogenes, which contribute to host colonization by remodeling peptidoglycan.
• Examples of Tat secreted proteins include phospholipase C of Pseudomonas aeruginosa, which requires Tat-based secretion to be functional.

Transport Systems in Gram-Negative Bacteria

• Gram-negative bacteria have two membranes (inner membrane and outer membrane), requiring unique mechanisms for protein secretion.
• Secretion systems can be divided into those that deposit proteins into the environment and those that deposit proteins into host cells.
• Multiple transport systems have evolved to transport proteins across the outer membrane, including Type I, Type II, Type III, Type IV, and Type VI secretion systems.

Type I Secretion System (T1SS)

• T1SS allows the translocation of unfolded proteins from the cytoplasm directly across the outer membrane without a periplasmic intermediate.
• The secreted proteins lack a typical signal peptide, but instead have a C-terminal secretion signal of ~60 amino acids.
• Examples of T1SS include E. coli and Pseudomonas.

Type II Secretion System (T2SS)

• T2SS allows the translocation of folded proteins from the periplasmic space across the outer membrane.
• The secreted proteins have an N-terminal signal sequence.
• Examples of T2SS include Acinetobacter.

Type III Secretion System (T3SS)

• T3SS allows the translocation of unfolded proteins from the cytoplasm directly across the outer membrane and into host cells.
• The secreted proteins have an N-terminal signal sequence.
• Examples of T3SS include EPEC, Shigella, and Salmonella.

Type IV Secretion System (T4SS)

• T4SS allows the translocation of unfolded proteins from the cytoplasm and periplasmic space across the outer membrane and into host cells.
• The secreted proteins have a C-terminal secretion signal.
• Examples of T4SS include Legionella and Coxiella.

Type VI Secretion System (T6SS)

• T6SS allows the translocation of proteins from the cytoplasm and periplasmic space across the outer membrane and into host cells.
• The secreted proteins have a C-terminal secretion signal.
• Examples of T6SS include Burkholderia and Pseudomonas aeruginosa.
• T6SS can be used as a mechanism for bacterial antagonism and inter-bacterial combat.

Type VII Secretion System (T7SS)

• T7SS is unique to Gram-positive bacteria and allows the translocation of proteins across the inner membrane and the bacterial cell wall.
• The secreted proteins have a C-terminal signal tag.
• Examples of T7SS include Mycobacterium tuberculosis and Staphylococcus aureus.
• T7SS is required for virulence.

Summary

• Multiple secretion systems exist in bacteria, including T1SS, T2SS, T3SS, T4SS, T5SS, T6SS, and T7SS.
• Each system has distinct characteristics, including the ability to transport folded or unfolded proteins, signal sequence locations, and target locations.
• Understanding these secretion systems is important for understanding bacterial pathogenesis and virulence.

Transport Systems in Gram-Negative and Positive Bacteria

• Both Gram-Negative and Positive bacteria have two common transport systems: the General Secretory Pathway (Sec Translocase Pathway) and the Twin Arginine Transport (TAT) pathway.
• The Sec Translocase Pathway is responsible for the secretion of unfolded proteins.
• The TAT pathway is responsible for the secretion of folded proteins.

Sec Translocase Pathway

• The Sec Translocase Pathway allows the transport of unfolded proteins across the inner membrane.
• Sec translocation can be co-translational or post-translational, depending on the protein and its interaction with Sec components.
• Proteins are targeted for the Sec system by a signal tag, a 20-30 residue sequence at the N-termini of proteins.

Tat Translocase System

• The Tat system allows the export of folded proteins from the cytoplasm.
• Recognition of proteins is mediated by a twin arginine tag at the N-termini of proteins, recognized by TatB/C.
• Recognition leads to the formation of a TatA pore (the TatA ring), through which the Tat protein translocates.

Transport Systems that Translocate Proteins into Host/Neighbour Cells

• Multiple secretion systems can translocate proteins into host/neighbour cells, including the T3SS, T4SS, and T6SS.

Type I-VI Secretion Systems

• Type I secretion system (T1SS): translocates proteins from the cytoplasm to the exterior, signaled by a C-terminus tag.
• Type II secretion system (T2SS): translocates folded proteins from the periplasm to the exterior, signaled by an N-terminus tag.
• Type III secretion system (T3SS): translocates proteins from the cytoplasm to the host cell cytoplasm, signaled by an N-terminus tag.
• Type IV secretion system (T4SS): translocates proteins from the cytoplasm to the host cell cytoplasm, signaled by a C-terminus tag.
• Autotransporter pathway (T5SS): translocates proteins from the periplasm to the exterior, signaled by an N-terminus tag.
• Type VI secretion system (T6SS): translocates proteins from the cytoplasm to the host cell cytoplasm, signaled by a secretion signal.

Transport Systems that Traverse the Outer Membrane of Gram-Negative Bacteria

• Multiple transport systems have evolved to allow the transport of proteins across the outer membrane from both the cytoplasm and periplasmic space.

Outer Membrane Vesicles (OMVs)

• OMVs bud out from Gram-negative bacteria, containing DNA, RNA, periplasmic proteins, and toxins.
• They are highly immunogenic, facilitating horizontal gene transfer, modulating the immune system, and acting as antimicrobials.
• Three main mechanisms of OMV production: blebbing (exocytosis), bacterial lysis, and membrane remodelling.

Membrane Vesicles (MVs) in Gram-positive Bacteria

• MVs protrude out from holes in the peptidoglycan layer, enabled by the production of endolysin, which weakens the peptidoglycan layer.
• MVs can form part of a stress response, with release up-regulated when iron is limited or antibiotics are present.

OMVs and Pathogenesis

• OMVs stimulate NOD-1 receptors, detecting Gram-negative peptidoglycan and driving an inflammatory response by activating NF-kb, leading to IL-8 production.
• This down-regulates antigens on the bacteria, helping it evade the immune system.
• Gram-negative bacteria can deliver peptidoglycan to host cells through invasion, Type 4 secretion, or OMVs.

OMVs and Immune Modulation

• OMVs can stimulate TLRs and modulate immunity through delivering sRNA.
• sRNA dampens the immune response by down-regulating cytokine production and neutrophil infiltration.
• OMVs can down-regulate antigen presentation through delivering peptidoglycan.

Other Functions of Bacterial Membrane Vesicles (BMVs)

• Nutrient acquisition
• Acting as decoys for antimicrobials
• Removing misfolded proteins
• Degrading antibiotics
• Serving as a free-floating energy source for compatible bacteria