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Type IV secretion systems (T4SS) Legionella: the archetype of the T4SS

LECTURE 6. Type IV secretion systems (T4SS) Legionella: the archetype of the T4SS Brief overview of type V, I and type II secretion systems.

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Type IV secretion systems (T4SS) Legionella: the archetype of the T4SS

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  1. LECTURE 6 Type IV secretion systems (T4SS) Legionella: the archetype of the T4SS Brief overview of type V, I and type II secretion systems

  2. Type IV secretion systems (T4SSs) are membrane-associated transporter complexes used by various bacteria to deliver substrate molecules to a wide range of target cells. T4SSs are involved in horizontal DNA transfer to other bacteria and eukaryotic cells, in DNA uptake from or release into the extracellular milieu, in toxin secretion and in the injection of virulence factors into eukaryotic host target cells by several mammalian pathogens.

  3. Legionella pathogenesis The lifecycle of L. pneumophila. In the environment L. pneumophila (red ellipses) is found (i) in association with biofilm communities and (ii) in planktonic form, and it can survive intracellularly in a wide range of protozoan hosts (as indicated by the differently shaped cells within the blue area) and environmental conditions. (iii) Exposure of humans to aerosolized contaminated water can result in the infection of alveolar macrophages. This can lead to disease, but is not transmitted between humans. (iv–ix) The intracellular lifecycle of L. pneumophila within eukaryotic host cells. (iv) In macrophages L. pneumophila can be internalized (v) Once within host cells, the bacterium quickly evades delivery to lysosomes and (vi) can prevent host cell death in infected macrophages. (vii) The vacuole in which L. pneumophila resides undergoes remodeling by intercepting host vesicular traffic flowing from the ER to the Golgi. (viii) The vacuole then undergoes fusion events with the ER and transforms into a specialized compartment that supports L. pneumophila replication. (ix) After several rounds of replication, the bacteria can leave the infected cell and go on to infect neighboring cells. Dot/Icm effectors involved in these processes are indicated in red.

  4. Type V secretion system: The autotransporters

  5. Type I secretion system: the paradigm is haemolysin in some E. coli strains Uropathogenic E. coli (UPEC) are the major cause of urinary tract infections (UTIs) and have the capacity to induce the death and exfoliation of target uroepithelial cells. This process can be facilitated by the pore forming toxin alpha-hemolysin (HlyA), which is expressed and secreted by many UPEC isolates

  6. TolC is also a component of the multi drug efflux pumps TolC is also involved in the secretion of siderophores!

  7. Some known proteins secreted by the type I secretion system Adenylate cyclase toxin-haemolysin (CyaA) is one of the major virulence factors of Bordetella pertussis, a Gram-negative pathogen causing whooping cough in humans. CyaA belongs to the same RTX (Repeat-in-Toxin) toxin family as the Escherchia coli haemolysin, HlyA Lipase LipA from Serratia marcescens is an enzyme that has an important biotechnological application in the production of a chiral precursor for the coronary vasodilator diltiazem. HasA is an extracellular heme binding protein that allows S. marcescens to scavenge heme from the host.

  8. Vibrio cholerae neuraminidase (VCNA) plays a significant role in the pathogenesis of cholera by removing sialic acid residues from higher-order gangliosides to an unmasked GM1, the essential receptor for cholera toxin.

  9. Type VI secretion system Type VI secretion

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