Protein secretion systems

Question 1

Protein secretion systems?

Answer 1

Specialized macromolecular nanomachines that secrete wide range of substrates.
Span double membranes (exception T5SS: solely in OM).

Question 2

Secretion into..?

Answer 2

• Extracellular space
• target cell
• remain ass with outer membrane (OM)

Question 3

Systems in gram-neg?

Answer 3

1. Indirect presentation: secretion into extracellular environment (Type I/II/IV)
2. Contact dependent translocation: mediates direct transport into host cell/bacterial cytosol (Type III, IV; VI)

Question 4

T1SS

Answer 4

Independent of sec system
Inner membrane ATPase+outer membrane factor+membrane fusion protein.
Secreted proteins not cleaved, transported unfolded.

Important: also involved in export of non-protein substrates (ions, drugs, polysaccharides)

Question 5

Example for T1SS

Answer 5

UPEC: a-Hemolysin secretion

Bordetella pertussis: CyA secretion

Pseudomonas aeruginosa: secretion of alkaline protease AprA and protease inhibitor AprL

Question 6

T2SS

Answer 6

General secretory pathway.
Translocation of proteins from periplasm across OM.
Proteins have to reach periplasm first. 
Sec dependent or Tat dependent.
Secreted proteins typically enzymes

Question 7

Important: Types of T2SS

Answer 7

1. Sec-dependent translocation into the periplasm: exportprotein unfolded
2. Tat-dependent translocation into the periplasm: exportprotein folded

Question 8

T2SS examples

Answer 8

V. cholerae: AB5 cholera toxin neuraminidase,
P. aeruginosa: pseudolysin exotoxin A,
K. pneumoniae: pullulanase

Question 9

T4SS

Answer 9

At least 12 protein components.
IM complex+core complex+OM complex
Translocation of single proteins(protein complexes/DNA and nucleoprotein complexes.

Question 10

Important: 3 functional groups of T4SS

Answer 10

1. Transfer of DNA from one cell to another (conjugation)
2. Protein transfer upon direct cell to cell contact between donor and recipient
3. Contact independent secretion of protein or DNA into environment

Question 11

Example for T4SS

Answer 11

H. pylori

Injection of Cytotoxin antigen A into gastric cells > gastric carcinome

Question 12

Example for contact-independent T4SS

Answer 12

B. pertussis: pertussis toxin

Question 13

T5SS

Answer 13

Important: localized only in OM

Bam complex.

Question 14

T6SS

Answer 14

Important: T6SS transports effector proteins from inside into other bacteria or eukaryotic cells

Similarities with T4 phages (T4 phage injects DNA from outside)

Question 15

T3SS

Answer 15

Independent of sec, membrane ass ATPase, secreted proteins not cleaved (like T1) and require chaperones (like T2).

Important: T3SS translocates effector proteins into cytosol of eukaryotic cells (syringe)

Question 16

T3SS

Answer 16

Independent of sec, membrane ass ATPase, secreted proteins not cleaved (like T1) and require chaperones (like T2).

Important: T3SS translocates effector proteins into cytosol of eukaryotic cells (syringe)

Question 17

Example for T3SS

Answer 17

Yersinia. Infect macorphages > in lymphoid tissues: T3SS required for survival/replication. Inject effector molecules into the phagocytes > inhibit phagocytosis.
Export Yops.

Important: T3SS is able to antagonize uptake of Yersinia by phagocytes > delayed innate immune response > delayed interference between innate and adaptive immune response.

Question 18

Yops

Answer 18

Yersinia outer proteins. Exported by T3SS. Translocator Yops B/D insert into host membrane and function as syringe to transport effector Yops O/H/M/T/J/E.

Question 19

SS of Salmonella

Answer 19

T3SS-1 and T3SS-2.

Important: effector proteins of both T3SS act in concert to invade intestinal cells and establish an intracellular replication permissive niche.

1: expressed when bacteria move extracellularly (inject effectors into intestinal cells > take up)
2: expressed when bacteria reside in vacuole in host cell

Question 20

Types + examples + secreted proteins

Answer 20

1: E. coli > HlyA
2: V.cholerae > AB cholera toxin
3: Y. enterocolitica > YOPs
4: H. pylori > CagA
5: N. meningitidis > NaIP
6: Ps. aeruginosa > Tse

Question 21

Type + Secretion * Substrate

Answer 21

1: release > protein/DNA/others
2: release > proteins
3: injection > protein
4: release/injection > protein/DNA
5: release/OM > protein
6: release/injection > protein

Question 22

Chlamydia SS?

Answer 22

T3SS.
Expressed on surface of elementary bodies (small, infectious, resistant to environment) not reticulate bodies (non infectious, intracellular, replicaitng)

Question 23

Which SS use sec-dependent protein delivery into the periplasmic space?

Answer 23

2,5