Bacterial Secretion Systems Flashcards
What are the 4 functions of secretion systems?
Protection = secrete toxins
Transport of structural proteins
Communication
Adhesion (fimbriae/pili)
What are the two mechanisms of secretion in Gram-negative bacteria?
One-step process = across the cell membrane and outer membrane in one step
Two-step process = export into the periplasm (Sec/Tat system) and then export across the outer membrane
What are the secretion systems used in one-step and two-step processes in Gram-negative bacteria?
One-step = T3SS, T4SS, T6SS
Two-step = T2SS, T5SS
What is the mechanism of secretion in Gram-positive bacteria?
Secreted proteins are commonly translocated across the CM by the Sec pathway or Tat pathway
What does the Sec system do?
Translocates unfolded proteins
Recognizes a hydrophobic leader sequence and is present in the cytoplasm of all bacteria
What does the Tat system do?
Transport folded proteins
Present in many bacteria and associate with proteins with cofactors
What is the energy source for both the Sec and Tat systems?
ATP
What does T1SS do?
They are dedicated to transporting one or a few unfolded substrates that range in function
Substrates are generally sec-independent and typically contain a C-terminal signal sequence that is recognized by T1SS and remains uncleaved
What are the 3 major components of the T1SS?
ABC transporter
MFP = membrane fusion protein
OMP = outer membrane protein transporter
What does the MFP of T1SS do?
Connects and coordinates transport across the CM and the OM
What provides the energy from T1SS?
ATP hydrolysis
What do OMFs provide?
A trans-periplasmic channel penetrating the outer membrane and connects to the MFP
What connects the OMF and the ABC in the periplasmic space of T1SS?
MFP
What does T1SS secrete from UPEC and what does it do?
Alpha-hemolysin which allows further invasion of the urinary tract
What is the T1SS toxin, MARTX, secreted from and what does it do?
V. cholera
Facilitates colonization of the small intestine by destroying host actin cytoskeleton
What Gram stain is T2SS found in?
Gram negative
What is the T2SS also known as and why?
The Sec-dependent system
Many proteins that pass through the T2SS must first reach the periplasm via the Sec pathway
Which pathogens require T2SS for virulence?
V, cholera, L, pneumonphila, enterotoxigenic E. coli
What are some virulence determinants secreted via the T2SS?
The ADP-ribosylating toxins of E. coli
Cholera toxin
Exotoxin A of P. aeruginosa
How does T2SS work?
In the CM, there is a platform that anchors T2SS
Unfolded proteins enter the periplasm via Sec and folds in the periplasm
The outer membrane complex is a complex of secretion that transports the folded proteins
Which bacteria are type III secretion systems found in?
Gram-negative bacteria - both pathogenic and non-pathogenic
What is the machinery in type III secretion systems?
The injectisome
Delivers effector proteins across bacterial and host membranes into the cytosol of host cells
What host cell functions do T3SS secretion systems modulate and how many membranes does it cross?
Immune and defense responses
3 membranes, CM + OM + target PM
What is the structure of injectisomes?
Composed of a series of basal rings that span the bacterial inner and outer membranes and are connected to a hollow needle (in Yersina) or filament (in Salmonella)
Each structure is tipped with a translocation pore that is inserted into the plasma membrane of the target cell
What energizes injectisome transport?
A conserved ATPase associates with the bacterial base of the injectisome and energizes transport
What do the classes of chaperones do to injectisomes?
Two classes aid in the assembly of the injectisome
A third class assist in translocation of effector proteins
What are many T3SS substrates similar to?
Eukaryotic proteins
What is the most widespread secretion pathway for the transport of molecules across the outer membrane of Gram-negative bacteria?
T5SS
What do proteins to be secreted from T5SS contain?
Beta barrel structure that insert themselves in the outer membrane
How does the protein get through the channel of T5SS?
A cleavage separates the channel from the protein to be transported
What are some adhesins that are secreted from T5SS?
YadA of Yersinia
AIDA-I and Ag43 of E. coli
What can be secreted from T5SS?
Adhesins, toxins, proteases
What is the function of UpaG of UPEC?
Adhesin that allows adherence to urinary tract
Promotes bacterial cell aggregation
How many membranes does T6SS cross?
3 - CM, OM, target membrane
What were T6SS and T3SS likely to evolve from?
Integrated prophage systems
Is there a clear link to virulence in T6SS?
No, may be involved in bacterial warfare though
What does T6SS constitute?
A phage-tail-spike-like injectisome
What is used to inject viral DNA into the host by T6SS?
A syringe-like process
What does T6SS have homology to?
Phage neck and tip
What is T7SS?
A specialized secretion apparatus that is required for the virulence of mycobacteria
Where have T7SS gene clusters been found?
In the following Gram-positive bacteria
-S. aureus
-L. monocytogenes
-B. subtilis
What is the causative agent of tuberculosis?
Mycobacterium tuberculosis
What does the cell envelope of mycobacteria consist of?
A plasma membrane (like an IM)
A periplasmic space that contains peptidoglycan and arabinogalactan
A mycomembrane
What are mycomembranes and what do they allow?
A thick, complex outer membrane that contains a waxy lipid coat of mycolic acids which allows for immune evasion and resistance to antibiotics
How does TB get to its target?
It is an airborne pathogen that gets phagocytized by macrophages
The bacteria replicates in the macrophage and dendritic cells then deliver the bacteria to the lymph nodes
Once in the lymph nodes, bacteria can leave cells and enter the blood and leave behind tubercules (scarring) that will restrict respiratory functioning
How does TB evade the immune system?
During the dormant state, it escapes immune defenses
It inhibits phagosome maturation as well as translocating from the phagolysosomes to the cytosol of the alveolar macrophage
Prevents inflammation
What does inhibition of the phagosome
Allows replication in endosomes without being trafficked into lysosomes
What are 2 substrates of T7SS?
ESX-1 = phagosomal escape
ESX-5 = host cell lysis
