AB5 toxin
The AB5 toxins are six-component protein complexes secreted by certain pathogenic bacteria known to cause human diseases such as cholera, dysentery, and hemolytic–uremic syndrome.
[4] This family is also known as Ct or Ctx, and also includes the heat-labile enterotoxin, known as LT.[5] Cholera toxin's discovery is credited by many to Dr. Sambhu Nath De.
[8] The bacterium Bordetella pertussis was first identified as the cause of whooping cough and isolated by Jules Bordet and Octave Gengou in France in 1900.
[13] It produced by strains of STEC that do not have the locus of enterocyte effacement (LEE),[14] and is known to cause hemolytic-uremic syndrome (HUS).
It is called a subtilase cytotoxin because its A subunit sequence is similar to that of a subtilase-like serine protease in Bacillus anthracis.
[15] The subtilase cytotoxin A subunit (subA, Q6EZC2) is a protease known to cleave binding immunoglobulin protein (BiP), leading to endoplasmic reticulum stress and cell death.
[5] The A1 chain for cholera toxin catalyzes the transfer of ADP-ribose from Nicotinamide adenine dinucleotide(NAD) to arginine or other guanidine compounds by utilizing ADP-ribosylation factors (ARFs).
In the absence of arginine or simple guanidino compounds, the toxin mediated NAD+ nucleosidase (NADase) activity proceeds using water as a nucleophile.
Following separation, the A1 domain unfolds and is redirected back to the cytosol where it refolds[5] and catalyzes ADP-ribosylation of certain G protein alpha subunits.
[23] Shiga toxin is also brought to the golgi apparatus before being directed to the endoplasmic reticulum for PDI to cleave the disulfide bond.
B subunits of the AB5 toxins have the affinity towards binding glycan which some type of tumors seem to possess making it an easy target.
This allows the toxin to promote immunological responses such as IgG2a, IgA, and Th17 to fight for instance gastric Helicobacter pylori infection when a vaccine is given.
For example, systemic immunization along with co-administered intra-nasal delivery of virus-cholera toxin conjugate vaccine induced a virus-specific antibody response and showed some degree of protection to the upper respiratory tract from Sendai virus.
[27] New advancements in biotechnological experimental methods such as the use of Bessel beam plane illumination microscopy and FRET-based sensor molecules can better demonstrate dynamic structures of gap junction plaques.
The response can then be recorded using cAMP concentration fluctuations in gap junction-coupled cells using FRET-based sensor constructs.
Research suggests that CDRs could perhaps be linked with rapid rearrangement of lipids and protein in connexin channels within the gap junction plaques.
This characteristic has been utilized to study the role of the cellular BiP itself, along with Endoplasmic-reticulum-associated degradation in stressed HeLa cells.
