1. Bacterial protein secretion systems
Many proteins need to be transported across the bacterial membrane
These include flagella and pilus subunits
Gram negative bacteria have evolved several systems for the secretion of proteins to the external environment

2. Bacterial protein secretion systems
Different systems are named according to the order in which they were discovered
i.e. Type I, II, III, IV, etc.

3. Gram negative protein secretion systems

4. Gram negative protein secretion systems

5. Sec-dependent pathway
Also known as the general secretory pathway (GSP)
Most commonly used system to transport proteins across plasma membrane or integrate them into the membrane
Used by both gram positive and gram negative bacteria

6. Sec-dependent pathway
System composed of both cytosolic and membrane-bound proteins
Secreted proteins contain N-terminal signal sequence
Chaperone protein binds to sequence and guides protein to transport machinery or translocon

7. Sec-dependent pathway
Chaperones include SecB and signal recognition particle (SRP)
Chaperones release preprotein which binds to SecA

8. Sec-dependent pathway
SecA translocates preprotein through SecYEG complex
Hydrolysis of ATP drives translocation
After emerging from the membrane, signal peptide is removed by signal peptidase

9. Type II secretion systems
Found in many gram-negative bacteria, including species of Erwinia, Pseudomonas and Vibrio
Used for the secretion of proteins through the outer membrane
Composed of as many as 14 different proteins (both inner and outer membrane-localized)

10. Type II secretion systems
Outer membrane protein forms a channel through which protein can pass
Family of proteins referred to as secretins

11. Secretins

12. Type I secretion systems
Also known as ABC protein secretion pathway
ABC = ATP-binding cassette
Secretion is independent of the sec pathway

13. Type I secretion systems
Used for the secretion of various enzymes and toxins including -hemolysin
Secreted proteins contain a C-terminal (noncleavable) signal sequence

14. Type I secretion systems
Are composed of only three different proteins
1. ATP -binding inner membrane protein
2. Outer membrane channel-forming protein
3. Membrane fusion protein

15. Type I secretion systems

16. Type I secretion systems
Proteins transported across both membranes in a single step
Energy for translocation derived from hydrolysis of ATP

17. Type III secretion systems
Found in a number of gram-negative bacteria
Bacteria with TTSS always exhibit intimate contact with host cells
Systems designed to both secrete and translocate or “inject” proteins into host cells

18. Type III secretion systems
Composed of at least 20 different proteins
Include cytosolic, membrane-bound and secreted proteins
Membrane proteins form a structure similar to the flagella basal body named the needle complex

19. Type III secretion systems
Outer membrane component of needle complex belongs to the secretin family of proteins
Proteins transported across both membranes in a single step
Hydrolysis of ATP provides energy for translocation

20. Type III secretion systems

21. Type III secretion systems

22. Type III secretion systems

23. Type III secretion systems
Many protein required for secretion through needle complex are similar to flagella assembly proteins
TTSSs likely evolved from bacterial flagella systems

24. Type IV secretion systems
Can be used to transfer proteins or DNA from one cell to another
Transfer proteins to eukaryotic host cells
Transfer plasmids to bacterial cells (conjugation)

25. Type IV secretion systems
Composed of several proteins that span the entire cell wall
Hydrolysis of ATP provides energy for transport
Found in many bacterial pathogens including species of Legionella, Bordetella and Helicobacter

26. Conjugal pilus
Several morphologically distinct pili
Appear to function as adhesins rather than transfer conduits
Retraction of pilus pulls cells close together

27. Type IV secretion/ autotransporters
Transport through inner membrane is sec-dependant
All substrates carry sec-signal sequence
Proteins divided into three domains i) sec signal sequence, ii) passenger domain, iii) -barrel domain

28. Type IV secretion/ autotransporters

29. Type IV secretion/ autotransportersOM IM
ATP
ADP
Sec Y E G
SecA
SecB N C

30. Gram negative protein secretion systems