Bacterial secretion systems transport proteins across cell membranes. There are seven main types: T1SS through T7SS. T1SS, T2SS, T3SS, T4SS, and T5SS are found in gram-negative bacteria and transport proteins through the inner and outer membranes. T1SS consists of an ABC transporter, MFP, and OMF proteins. T2SS transports folded proteins using an outer membrane complex, inner membrane platform, ATPase, and pseudopilus. T3SS has a base complex, needle, and translocon. T4SS and T6SS can transport substrates between bacteria and host cells. T5SS comes in three classes: autotransport

1. Bacterial secretion system
Ahtesham Hanifi
I200602

2. • Transport of proteins from the cytoplasm into other compartments of the cell, the
environment, and/or other bacteria or eukaryotic cells—a process known as protein
secretion.
• Two pathways : a. Sec ( secretion) pathway,
b. Twin arginine translocation ( Tat ) pathway.
• Seven types of secretion system : T1SS, T2SS, T3SS, T4SS, T5SS, T6SS and T7SS.
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3. The Sec secretion pathway
• Mainly translocate proteins in their unfolded state.
• This pathway relies on presence of signal sequence at N-terminal of nascent
polypeptide.
• Two types of signals :
a. SecB - specific signal sequence = Directs protein transport outside of cell.
b. SRP – specific signal sequence = proteins meant to remain in the inner
membrane.

4. • Notable gram negative bacteria that uses Sec dependent secretion pathway to
transport virulence factor : Vibrio cholerae, Klebsiella pneumoniae, and Yersinia
enterocolitica .
• Gram positive bacteria having Sec dependent secretion pathway to transport
virulence factor : Staphylococcus aureus and Listeria monocytogenes .
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5. The Tat secretion pathway
• Mainly concerned with secretion of folded proteins.
• Consists with two or three subunits : TatA, TatB and TatC (in Gram-positive
bacteria, TatA and TatB are combined into one multifunctional protein).
• Signal sequence contains a pair of twin arginine ( -X-R-R- ) in N-terminal of folded
proteins.
• Pathogenic bacteria having functional Tat pathway to transport virulence factor :
Pseudomonas aeruginosa, Yersinia pseudotuberculosis , and E. Coli O157:H7.

6. • The best example of Tat pathway secretion is Phospholipase C by MTb that helps
in intracellular survival of bacterium by suppressing hosts’s immune response.
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7. Types of secretion system in bacteria
1. Type 1 secretion system ( T1SS )
• Found in large number in gram negative pathogenic bacteria.
• Closely resemblance with ATP binding cassette ( ABC ) transporters family.
• Signal sequence found on C-terminus of polypeptide.
• Three essential structural components of T1SS :
i). ABC transporter protein : Found in inner membrane and catalyzes the ATP to
release energy to transport substrates.

8. ii). Membrane fusion protein ( MFP ) : Linking the inner and outer membrane. The
MFP associates with the ABC transporter in the inner membrane and spans the
periplasm to associate with the OMF. N-terminus of MFP play a role in substrate
selection.
iii). Outer membrane factor ( OMF ) : Found in outer membrane and generates a pore
through which substrate can cross the plasma membrane in an unfolded state.
• The best studies T1SS substrate is HlyA hemolysin protein of uropathogenic E.coli.
• Vibrio cholerae uses T1SS to secrete MARTX toxin – a virulence factor.

9. 2. Type 2 Secretion System ( T2SS ).
• Found mostly in gram negative bacteria .
• Transport folded proteins from periplasm to outside of cell.
• T2SS located in outer membrane, hence protein needs to come in outer membrane
from cytosol through Sec or Tat pathway.
• Consists of four components of T2SS, which are :
i). Outer membrane complex : Found in outer membrane, where it serves as channel to
translocate T2SS substrate protein.

10. ii). Inner membrane plateform : plays crucial role proteins secretion process by
communicating with the secretin, pseudopilus, and ATPase to coordinate export of
substrates.
iii). ATPase region : located in cytoplasm and provides energy to power transport.
iv). Pseudopilus region : It acts as piston to provide push force to T2SS folded protein.
• Vibrio cholerae uses T2SS to release its cholera toxin.
• Bacteria having functional T2SS are : L. pneumophila, E. coli and K. pneumoniae.

11. 3. Type 3 Secretion System ( T3SS ).
• Found in large number in gram negative pathogenic and symbionts bacteria.
• Secrets wide variety of protein across both inner and outer membrane of bacterium.
• Composed of three main components:
i). Base complex : The base complex contains cytoplasmic components and spans the
inner and outer membrane, forming a socket-like structure consisting of several rings
with a centre rod.
ii). Needle : an intermediate hollow component.

12. iii). Translocon : Provide passages to T3SS substrate.
• Pathogenic bacteria having type 3 secretion system are : Yersinia, Salmonella, and
Shigella.
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13. 4. Type 4 Secretion System ( T4SS )
• T4SSs are ancestrally related to bacterial DNA conjugation system .
• Secrets substrates into wide range of cells including other bacteria and eukaryotic
cells.
• Largely found in gram negative bacteria.
• Agrobacterium tumefacium uses its T4SS to transports its oncogene into plants.
• T4SSs plays a pivotal role in wide range of bacteria to transport virulence factor,
such as Neisseria gonorrhoe, L. Pneumophila, Brucella suis, and Helicobacter
pylori.

14. 5. Type 5 Secretion System ( T5SS )
• Found in outer membrane of both, gram positive and gram negative bacteria.
• Having unique substrate possessing beta barrel domain.
• Because, found in outer membrane hence it is Sec pathway dependent secretion
system.
• Most notable T5SSs substrate is IcsA protein of Shigella flexneri and YadA of
Yersinia enterocolitica.

15. • Three classes of T5SSs are :
A. Auto transporter secretion: Contain components that allow them to secrete
themselves .
B. Two partner secretion : Found in gram negative bacteria and resposible for
secretion of large virulence protein such as filamentous hemagglutinin of
Bordetella pertussis.
C. Chaperone–usher secretion : Chaperone–usher systems are commonly used to
assemble pilins on the surface of Gram-negative bacteria, such as the P. Pilus of
uropathogenic E. coli.

16. 6. Type 6 Secretion System ( T6SS )
• Most recent discovered bacterial secretion system.
• Conserved in wide variety of gram negative bacteria.
• capable of transporting effector proteins from one bacterium to another in a
contact-dependent manner.
• mechanisms of how these T6SSs contribute to survival in the environment (and in
mammalian infection) have not been determined.

17. 7. Type 7 secretion system ( T7SS )
• Found mainly in gram positive bacterial species including Mycobacterium and
Cornybactria .
• Its mechanism and other factors are under research because of recently discovered.
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