Bacterial Toxins

Yogi Khoirul Abror

Departement Of Immunology Postgraduate Programme
Airlangga University
Subject
 Introduction
 Toxins Acting on Immune System
 Toxins Acting on Surface Molecule
 Toxins Acting on the cell Membrane
 Large Pore- Forming Toxins
 Small Pore-Forming Toxins
 RTX Toxins
 Membrane Pertrubing Toxins
 Other Pore Performing Toxins
 Insecticidal Toxins
Subject
 Toxins Acting on Protein Synthesis
 Toxing Acting on Signal Transduiction
 Pertusis Toxin
Introduction
 Toxins were first bacterial virulence factors that have a target in
most compartement of eukaryotic cells.

 First categories is toxins that acting on the surface of eukaryotic cell

simply by touching important receptors, by cleaving surface-
exposed molecules. or by punching holes in the cell membrane,
thus breaking cell permeability.

 Second categories is toxin that have intracellular target and hence

need to cross the cell membrane.

 Third categories is toxins that have intracelluer target and are

directly delivered by the bacteria into eukaryotics cells.
Three Types Of Toxins
Toxins act on Intracelluer Targets
Toxins injected the eukaryotic cell
Toxins act on the cell surface

Diphteria
Botulinium Toxic
Tetanus
Signal

Cholera
Shigela
LT
Toxins Acting on Immune System
( Superantigens )
 Bacterial superantigens, also konw as pyorgenic toxins that mostly
produced by Staphylococcus aureus and Streptococcus pyogenes. Toxins
produced by its bacteria is SEA-SEI, TSST-1, SPEA, SPEC, SPEL, SPEM, SSA, and
SMEZ which is their activity is binding to MHC class II and to Vb or Vg T Cell
Receptors.

 Mam is a toxcin that produced by Mycoplasma arthritidis which contribute

to the acute and chronic inflamation

 YPMa is a toxcin produced Yersinia pseudotuberculosis strains

Toxins Acting on Immune System
( Superantigens )
 Another toxins that have long been known a superantigen are SPEB
produced by Staphylococcus pyogenes. SPEB causes cytopathic effect on
human endothelial cells and represent a critical virulence factor in human
inection.

 ETA and ETB of Staphylococcus aureus are produced during the

exponential phase growth and excerted form colonisizing staphylococci
before being absorbed inti systemic sirculation.
Toxins Acting on Surface Molecule
 Bacteriocide fragilis enterotoxin (BFT) is a toxcin produced by
Bacteriocides fragilis.

 BFT causes diarrhea and fluid accumulation in ligated ileal loops

 BFT belongs to large familyof bacterial metalloprotease that usually

cleave proteins of the extracellular matrix Pseudomonas aeroginusa
and Aeromonas hydrophiliaelastases (Amino peptidase and AhyB
and Clostridium hystolitycum collagnase (ColH)
Toxins Acting on the cell Membrane
 Protein toxins forming pores in biological membrane occur frequently in
gram positive and gram negative bacteria

 Pore forming toxins also known as lytic factors , work by punching holes in
the plasma membrane thus break the permebeality barrier that keeps
macromolecule and small solutes within the cells
Large Pore- Forming Toxins

 Toxins belongs to this group produced by Streptococcus pyogenes (SLO),

S.pneumoniae (Pneumolysin) , C. Perfingens (PFO) and listeria
monocytogenes (LLO).
Small Pore-Forming Toxins
 Creating very small pores (1 – 1,5 nm) in the memrane of host cell, thus
allowing their selective permebilization to solutes with a molecular mass less
than 2 kDa.

 Alpha toxins (A-hemolysin) is the group of small pore forming toxins

produced by Staphylococcus aures. These toxin bind human erytrhocytes,
monocytes, and endothelial cell at high concentration caused membrane
rupture and cell lysis and death.

 Another toxins belogs to this group are Alveolysin (B.Alveis), ALO

(B.Antrhacis), and PVL Leukocidin (S.aureus).
RTX Toxins

 Toxins belongs to this group is Hemolysin II and CytK Produced by B.

Cereus and HlyA produced by E.Coli.

 Hemolysin II and CytK act on cell membrane permebilization,

Hemolysin II causes hemolytic activity and cytK causes necrotic
enteritis.
Membrane Perturbing Toxins
 Toxins belongs to this group is Apxl, Apxll, Apxlll, LtxA, and LktA.

 Apxl, Apxll and Apxlll Toxins produced by A. Peuropneumoniae, this toxin

causes lysis of erythrocyte and other nuvleated cells.

 LtxA toxins produced by A. actinomycetemcomitans causes apoptosis if

the cell.

 LktA toxins produced by p. haemollytica causes ruminant leukocyte.

Insecticidal Toxins
 The class of insecticidal proteins konown as delta endotoxins produced by
spesies of Bacilus thuringiensis.

 The toxins exert their activity by making pores in the epithelial cell
membrane of the insect midgut.

 Delta endotoxins form two multigenic families cry and cyt. Member of cry
families are toxic to insect of Lepidoptera, Diptera, and Coleoptera,
whereas the cyt families was lethal spesifically to the larvae of dipteran
insects.

 Because of the toxicity of delta endotoxins to several sepsies of insects,

delta endotoxins are formulated inti commercial insecticides.
Toxins Acting on Protein Synthesis
 Toxins belongs to this group are able cause rapid cell death at etremely
low concentration.

 Diphteria toxins (DT) produced by Corynebacterium diphteria and

Pseudomonas aeruginusa exotoxin A (PAETA) produced by Pseudomonas
aeruginusa both exert their toxixcity by transferring the ADP – Ribose moiety
to a postranslationally modified histidine residu of the cytoplasmic
elongation factor 2 (EF2) of eukaryotic cells. This reaction leads to the
formation of a completely inactive EF2-ADP ribose complex, which is
causes inhibition of protein synthesis and cell death.
Toxins Acting on Signal Transduction
 Signal transduction is an essential mechanism to survive of any living
organism.

 Signal received from the outside stimulate receptors on the cell surface
and transmitted across the cell membrane using two types.

 Type one, tyrosine phosphorylation of the cytoplasmic receptor, initiates a

cascade of intracellular signaling.

 Type two, modification of a receptor coupled GTP Binding protein that

tranduced signal to various enzymeswich respond with the release of cyclic
AMP ( cAMP), inositol triphosphate and diacyglycerol. Accumulation of this
products alters the norlma equilibrum and provokes malfunction.
 Toxins Acting on Signal Transduction
Toxins Name of Bacteria
PT Bordetella pertusis
CT Vibrio cholerae
LT E. coli
Alpha toxins C. perfringens
Toxins A and B C. diffocile
Adenylate cyclase Bordetella pertusis
Antrax edema factor B. antrachis
Cytotoxin necrotizing factor 1 and 2 E.coli
DNT Bordetella pertusis
Pertusis Toxins
 Pertusis Toxins ( PT ) is a protein 105 kDa produced by Bordetella pertusis. Its
belongs to the A/B class of ADP-ribosylating toxins and composed five
distinct sub units ( S1 – S5 ).

 The A domain acts by ADP-ribosylating their GTP binding protein. The

consequence of ADP-ribosylation is uncoupling of G-proteins from their
receptors with the impact is an aletration of the response of eukaryotic cells
to exogenous stimuli and thus in a variety of invivo phenotypes, such as
leukocytes, histamine, sensitization, and increase insulin.

 The B domain is a nontoxic oligomer that binds the receptors on the

surface eukaryotic cells.
Conclusion

 Toxins were first bacterial virulence

 There are three types of toxins, toxins acting on cell surface, toxins
acting on intracellular targets, and toxins injected into eukryotics
cells.
Terima Kasih