This document provides an overview of bacterial toxins, classifying them into two main categories: exotoxins that act on specific host sites, and toxins that act intracellularly or on the cell surface. It describes various toxin classes, including their mechanisms of action, examples of toxins that fall into each class, and the consequences of their activities. The classes discussed include toxins that act on the immune system, surface molecules, through pore formation, using the RTX mechanism, by perturbing membranes, targeting insects, and those acting intracellularly on protein synthesis, signal transduction pathways, and other targets. Specific toxins are given for each class along with their producing organisms and molecular activities.
2. Introduction
Toxins were the first bacterial virulence factors to
be identified and were also the first link between
bacteria and cell biology.
3. Introduction
Cellular microbiology was, in fact, naturally born
a long time ago with the study of toxins, and only
recently, thanks to the sophisticated new
technologies, has it expanded to include the study
of many other aspects of the interactions
between bacteria and host cells.
9. Injected into
eukaryotic cells
Protein synthesis
Mediators of apoptosis
Surface molecules
Signal transduction
Inositol phosphate
metabolism
Cell membrane
Class
Acting on
intracellular
targets
Immune system
(Superantigens)
Target
Acting on the
cell surface
Cytoskeleton structure
Cytoskeleton
Large pore- forming toxins
Intracellular trafficking
Signal transduction
Small pore- forming toxins
RTX toxins
Membrane-perturbing
toxins
Other pore- forming
toxins
Insecticidal toxins
Unknown
mechanism of
action
10. Toxins acting on the cell surface:
Immune system (Superantigens)
Superantigens are bacterial
and viral proteins that share
the ability to activate a large
fraction of T-lymphocytes.
11. Toxins acting on the cell surface: Immune system (Superantigens)
Toxin
Organism
Activity
Consequence
Binding to MHC class II
molecules and to Vβ or Vγ
of T cell receptor
T cell activation and
cytokines secretion
MAM
Mycoplasma
arthritidis
Binding to MHC class II
molecules and to Vβ or Vγ
of T cell receptor
Chronic inflammation
YPMa
Yersinia
pseudotuberculosis
Binding to MHC class II
molecules and to Vβ or Vγ
of T cell receptor
Chronic Inflammation
S. pyogenes
Cysteine protease
Alteration in
Immunoglobulin binding
properties
S. aureus
Trypsin-like serine
proteases
T-cell proliferation,
intraepidermal layer
separation
SEA-SEI, TSST-1, SPEA,
Staphylococcus
SPEC, SPEL, SPEM, SSA, and aureus and Streptococcus
SMEZ
pyogenes
SPEB
ETA, ETB, and ETD
13. Toxins acting on the cell surface:
Surface molecules
BFT enterotoxin: The pathogenicity of ETBF is
ascribed to a heat-labile ∼20-kDa toxin (B.
fragilis toxin [BFT], also called fragilysin).
This toxin binds to a specific intestinal epithelial
cell receptor and stimulates cell proliferation.
15. Toxins acting on the cell surface: Surface molecules
Toxin
Organism
Activity
Consequence
BFT enterotoxin
Bacteroides fragilis
Metalloprotease, cleavage
of E-cadherin
Alteration of epithelial
permeability
AhyB
Aeromonas
hydrophyla
Elastase,
metalloprotease
Hydrolization of casein and
elastine
Aminopeptidase
Pseudomonas
aeruginosa
Elastase,
metalloprotease
Corneal infection,
inflammation and
ulceration
ColH
Clostridium
histolyticum
Collagenase,
metalloprotease
Collagenolytic activity
Nhe
Bacillus cereus
Metalloprotease and
collagenase
Collagenolytic activity
16. Toxins acting on the cell surface:
Pore-Forming
Protein toxins forming pores in biological membranes
occur frequently in Gram-positive and Gram-negative
bacteria.
Pore-forming toxins, also known as "lytic factors".
Some of them are also called "hemolysins“.
17. Toxins acting on the cell surface:
Large Pore-Forming Toxins
Generally secreted by diverse species of Grampositive bacteria.
Binding selectively to cholesterol on the
eukaryotic cell membrane.
18. Toxins acting on the cell surface: Large pore forming toxins
Toxin
Organism
Activity
Consequence
PFO
C. perfringens
Thiol-activated cytolysin,
cholesterol Binding
Gas gangrene
SLO
S. pyogenes
Thiol-activated cytolysin,
cholesterol Binding
Transfer of other toxins,
cell death
Induction of Lymphocyte
apoptosis
Membrane damage
Induction of Lymphocyte
Apoptosis
Complement activation,
cytokine production,
apoptosis
LLO
Pneumolysin
Listeria monocytogenes
S. pneumoniae
19. Toxins acting on the cell surface:
Small pore forming toxins
Creating very small pores 1-1.5 nm diameter.
Selective permeabilization to solutes with a molecular
mass less than 2 kDa.
20. Toxins acting on the cell surface: Small pore forming toxins
Toxin
Organism
Activity
Consequence
Alveolysin
B. alveis
Induction of lymphocyte Apoptosis
Complement activation, cytokine
production, apoptosis
ALO
B. anthracis
Induction of lymphocyte apoptosis
Complement activation, cytokine
production, Apoptosis
α-Toxin
S. aureus
Binding of erythrocytes
Release of cytokines, cell lysis, apoptosis
PVL leukocidin
(LukS-LukF)
S. aureus
Cell membrane permeabilization
Necrotic enteritis, rapid shock-like
syndrome
γ-Hemolysins
(HlgA- HlgB and
HlgC- HlgB)
S. aureus
Cell membrane permeabilization
Necrotic enteritis, rapid shock-like
syndrome
β-Toxin
C. perfringens
Cell membrane permeabilization
Necrotic enteritis, neurologic effects
21. Toxins acting on the cell surface:
RTX toxins
The RTX toxin family is a group of cytotoxins produced by
Gram-negative bacteria.
There are over 1000 known members with a variety of
functions.
22. Toxins acting on the cell surface:
RTX toxins
The RTX family is defined by two common features:
characteristic repeats in the toxin protein sequences, and
extracellular secretion by the type I secretion system
(T1SS).
The name RTX (repeats in toxin) refers to the glycine and
aspartate-rich repeats located at the C-terminus of the
toxin proteins.
23. Genomic Structure
The toxin is encoded by four genes, one of which, hlyA,
encodes the 110-kDa hemolysin. The other genes are
required for its posttranslational modification (hlyC) and
secretion (hlyB and hlyD).
24. Toxins acting on the cell surface: RTX toxins
Toxin
Organism
Activity
Consequence
Hemolysin II
B. cereus
Cell membrane permeabilization
Hemolytic activity
CytK
B. cereus
Cell membrane Permeabilization
Necrotic enteritis
HlyA
E. coli
Calcium-dependent formation of transmembrane Pores
Cell permeabilization and lysis
25. Toxins acting on the cell surface:
Membrane perturbing toxins
Soap like structure.
The toxin binds nonspecifically parallel to the surface of
any membrane without forming transmembrane channels.
Cells first become permeable to small solutes and
eventually swell and lyse, releasing cell intracellular
content.
26. Toxins acting on the cell surface: Membrane perturbing toxins
Toxin
Organism
Activity
Consequence
ApxI, ApxII, and ApxIII A.pleuropneumoniae
Calcium-dependent formation of
transmembrane Pores
Lysis of erythrocytes and
other nucleated Cells
LtxA
A.actinomycetemcomitans
Calcium-dependent formation of
transmembrane Pores
Apoptosis
LtxA
P.Haemolytica
Calcium-dependent formation of
transmembrane Pores
Activity specific versus
ruminant leukocytes
27. Toxins acting on the cell surface:
Other pore forming toxins
Like other functionally related toxins, aerolysin changes
its topology in a multi-step process from a completely
water-soluble form to a membrane-soluble heptameric
transmembrane channel that destroys sensitive cells by
breaking their permeability barriers.
28. Toxins acting on the cell surface: Other pore forming toxins
Toxin
Organism
Activity
Consequence
δ-Hemolysin
S. aureus
Perturbation of the lipid bilayer
Cell permeabilization and lysis
Aerolysin
A. hydrophila
Perturbation of the lipid bilayer
Cell permeabilization and lysis
AT
C. septicum
Perturbation of the lipid bilayer
Cellpermeabilization and lysis
29. Toxins acting on the cell surface:
Insecticidal toxins
The class of insecticidal proteins, also known as
δ-endotoxins, includes a number of toxins produced by
species of Bacillus thuringiensis.
These exert their toxic activity by making pores in the
epithelial cell membrane of the insect midgut.
30. Toxins acting on the cell surface:
Insecticidal toxins
δ-Endotoxins form two multigenic families, cry and cyt;
members of the cry family are toxic to insects of
Lepidoptera, Diptera and Coleoptera orders (Hofmann et al.,
1988),
whereas members of the cyt family are lethal specifically to
the larvae of Dipteran insects (Koni and Ellar, 1994).
Lepidoptera is a large order of insects that includes moths and butterflies.
True flies are insects of the order Diptera.
Coleoptera is an order of insects commonly called beetles.
31. Toxins acting on the cell surface: Insecticidal toxins
Toxin
Organism
Activity
Consequence
PA
B. anthracis
Perturbation of the lipid bilayer
Cell permeabilization and lysis
HlyE
E. coli
Perturbation of the lipid bilayer
Osmotic lysis of cells lining the Midgut
CryIA, CryIIA,
CryIIIA, etc
Bacillus thuringiensis
Destruction of the transmembrane
Potential
Osmotic lysis of cells lining the Midgut
CytA, CytB
B. thuringiensis
Destruction of the transmembrane
Potential
Osmotic lysis of cells lining the Midgut
BT toxin
B. thuringiensis
Destruction of the transmembrane
Potential
Cytocidal activity on human cells
32. Toxins Acting on Intracellular Targets
Class
The group of toxins with an intracellular
Acting on the
target (A/B toxins) contains many toxins
cell surface
with different structures that have only
one general feature in common: they are
Immune system
composed of two domains generally
(Superantigens)
identified as "A" and "B.“
Acting on
intracellular
targets
Injecte
eukaryo
Protein synthesis
Mediators o
Inositol ph
metab
Surface molecules
Signal transduction
Cell membrane
arget
Cytoskeleton structure
Cytoske
Large pore- forming toxins
Intracellular trafficking
Signal tran
Small pore- forming toxins
33. Toxins Acting on Intracellular Targets
The A domain is the active portion of the toxin; it usually
has enzymatic activity and can recognize and modify a
target molecule within the cytosol of eukaryotic cells.
The B domain is usually the carrier for the A subunit; it
bind the receptor on the cell surface and facilitates the
translocation of A across the cytoplasmic membrane.
34. Toxins acting on intracellular targets:
Protein synthesis
These toxins are able to cause rapid cell death at
extremely low concentrations.
This reaction leads to the formation of a completely
inactive EF2-ADP-ribose complex.
35. Toxins acting on intracellular targets:
Protein synthesis
A very important step in the elucidation of the mechanism
of enzymatic activity has been the determination of the
crystal structure for the complex of diphtheria toxin with
NAD.
Upon the addition of NAD to nucleotide-free DT crystals, a
significant structural change.
This change lead to recognition and binding of the
acceptor substrate EF-2.
This would explain why DT recognizes EF-2 only after NAD
has bound.
36. Toxins acting on intracellular targets: Protein synthesis
Toxin
Organism
Activity
Toxins acting on intracellular targets:
Corynebacterium diphtheriae
ADP-ribosylation of EF-2
PAETA P. aeruginosa
Protein synthesis ADP-ribosylation of EF-2
DT
SHT
S. dysenteriae
N-glycosidase activity on 28S RNA
Consequence
Cell death
Cell death
Cell death, apoptosis
37. Toxins acting on intracellular targets:
Signal transduction
Two types of transduction mechanism:
Tyrosine phosphorylation
Modification of a receptor-coupled GTP-binding protein
cyclic AMP
inositol triphosphate
diacylglycerol
39. Cholera toxin (CT) and E. coli heatlabile enterotoxins (LT-I and LT-II)
Cholera toxin (CT) and E. coli heat-labile enterotoxins (LTI and LT-II) share an identical mechanism of action and
homologous primary and 3D structures.
While V. cholerae exports the CT toxin into the culture
medium, LT remains associated to the outer membrane
bound to lipopolysaccharide.
The corresponding genes of CT and LT are organized in a
bicistronic operon and are located on a filamentous
bacteriophage and on a plasmid, respectively.
40. Clostridium difficile Toxins
Enterotoxin A (TcdA) and cytotoxin B (TcdB) of Clostridium
difficile are the two virulence factors responsible for the
induction of antibiotic-associated diarrhea.
The toxin genes tcdA and tcdB together with three
accessory genes (tcdC-E) constitute the pathogenicity
locus (PaLoc) of C. difficile.
41. Toxins acting on intracellular targets: Signal transduction 1
Toxin
Organism
Activity
Consequence
PT
Bordetella pertussis ADP-ribosylation of Gi
cAMP increase
CT
Vibrio cholerae
ADP-ribosylation of Gi
cAMP increase
LT
E. coli
ADP-ribosylation of Gi
cAMP increase
α-Toxin (PLC)
C. perfringens
Zinc-phospholipase C, hydrolase
Gas gangrene
Toxins A and B (TcdA and
TcdB)
C. difficile
Monoglucosylation of Rho, Rac,
Cdc42
Breakdown of cellular actin
stress fibers
Adenylate cyclase (CyaA)
B. pertussis
Binding to calmodulin ATP→cAMP
conversion
cAMP increase
42. Anthrax Edema and Lethal Factors
The EF and LF genes are located on a large plasmids.
Cleavage of the N-terminal signal peptides yields mature
EF and LF proteins.
LF, is able to cause apoptosis in human endothelial cells.
43. E. coli Cytotoxin Necrotizing Factors and
Bordetella Dermonecrotic Toxin
CNF1 & CNF2: produced by a number of uropathogenic
and neonatal meningitis-causing pathogenic E. coli
strains.
cnf1 is chromosomally encoded, cnf2 is carried on a
large transmissible F-like plasmid called "Vir“.
DNT is a transglutaminase, which causes alteration of
cell morphology, reorganization of stress fibers, and
focal adhesions on a variety of animal models.
44. Cytolethal Distending Toxins
HdCDT is a complex of three proteins (CdtA, CdtB and
CdtC) encoded by three genes that are part of an operon.
Members of this family have been identified in E. coli,
Shigella, Salmonella, Campylobacter, Actinobacillus and
Helicobacter hepaticus.
45. Toxins acting on intracellular targets: Signal transduction 2
Toxin
Organism
Activity
Consequence
Anthrax edema factor (EF)
B. anthracis
Binding to calmodulin ATP→cAMP
conversion
cAMP increase
Anthrax lethal factor (LF)
B. anthracis
Cleavage of MAPKK1 and MAPKK2
Cell death, apoptosis
Cytotoxin necrotizing
factors 1 and 2 (CNF1, 2)
E. coli
Deamidation of Rho, Rac and Cdc42
Ruffling, stress fiber
formation.
DNT
Bordetella species
Transglutaminase, deamidation or
polyamination of Rho GTPase
Ruffling, stress fiber
formation
CDT
Several species
DNA damage, formation of actin
stress fibers via activation of RhoA
Cell-cycle arrest,
cytotoxicity, apoptosis
46. Toxins acting on intracellular targets:
Cytoskeleton structure
The cytoskeleton is a cellular structure that consists of a
fiber network composed of microfilaments, microtubules,
and the intermediate filaments.
It controls a number of essential functions in the
eukaryotic cell:
exo- and endocytosis
vesicle transport
cell-cell contact
and mitosis
47. Toxins acting on intracellular targets:
Cytoskeleton structure
Most of them do it by modifying the regulatory, small G
proteins, such as Ras, Rho, and Cdc42, which control cell
shape.
48. Lymphostatin
Lymphostatin is a very recently identified protein in
enteropathogenic strains of E. coli
Lymphostatin selectively block the production of
interleukin-2, IL-4, IL-5 and γ interferon by human cells
and inhibit proliferation of these cells, thus interfering
with the cellular immune response.
49. Toxins acting on intracellular targets: Cytoskeleton structure
Toxin
Organism
Activity
Toxin C2 and related
proteins
C. botulinum
ADP-ribosylation of monomeric G actin Failure in actin polymerization
Lymphostatin
E. coli
Block of interleukin production
Chronic diarrhea
Block of interleukin production
Chronic diarrhea
Iota toxin and related
C. perfringens
proteins
Consequence
50. Toxins acting on intracellular targets:
Intracellular trafficking
Vesicle structures are essential in:
receptor-mediated endocytosis
and exocytosis
One example of exocytic pathway is that involving the
release of neurotransmitters
51. Mechanism of action of clostridial
neurotoxins (CNT)
Synaptosomal-associated protein 25 (SNAP-25)
52. Helicobacter pylori Vacuolating
Cytotoxin Vac A
This toxin is responsible for massive growth
of vacuoles within epithelial cells.
VacA can insert into membranes forming
hexameric, anion-selective pores.
53. Toxins acting on intracellular targets: Intracellular trafficking
Toxin
Organism
Activity
Consequence
TeNT
C. tetanii
Cleavage of VAMP/ synaptobrevin
Spastic paralysis
BoNT-B, D, G and F
neurotoxins
C. botulinum
Cleavage of VAMP/ synaptobrevin
Flaccid paralysis
BoNT-A, E neurotoxins
C. botulinum
Cleavage of SNAP-25
Flaccid paralysis
BoNT-C neurotoxin
C. botulinum
Cleavage of syntaxin, SNAP-25
Flaccid paralysis
Vacuolating cytotoxin
VacA
H. pylori
Alteration in the endocytic pathway
Vacuole formation,
apoptosis
NAD glycohydrolase
S. pyogenes
Keratinocyte apoptosis
Enhancement of GAS
proliferation
54. Toxins injected into eukaryotic cells
These bacteria intoxicate individual eukaryotic cells by
using a contact-dependent secretion system to inject or
deliver toxic proteins into the cytoplasm of eukaryotic
cells.
This is done by using specialized secretion systems that in
Gram-negative bacteria are called "type III" or "type IV,“.
55. Class
Toxins injected into eukaryotic cells:
Acting on
Acting on the
Mediators of apoptosis: IpaB in Shigella
intracellular
cell surface
targets
Shigella invasion plasmid antigen (Ipa) proteins: IpaA,
Immune
IpaB, IpaC, IpaD. system
Protein synthesis
(Superantigens)
Only IpaB is required to initiate cell death.
Mediators of apoptosis
Surface molecules
Signal transduction
Inositol phosphate
metabolism
Cell membrane
Target
Injected into
eukaryotic cells
Cytoskeleton structure
Cytoskeleton
Large pore- forming toxins
Intracellular trafficking
Signal transduction
Small pore- forming toxins
RTX toxins
Membrane-perturbing
toxins
56. Toxins injected into eukaryotic cells:
Mediators of apoptosis: SipB in Salmonella
An analog of Shigella invasin IpaB.
In contrast to Shigella, Salmonella does not escape from
the phagosome, but it survives and multiplies within the
macrophages.
Salmonella virulence genes are encoded by a chromosomal
operon named sip containing five genes (sipEBCDA).
57. Toxins injected into eukaryotic cells: Mediators of apoptosis
Toxin
Organism
Activity
Consequence
IpaB
Shigella
Binding to ICE
Apoptosis
SipB
Salmonella
Cysteine proteases
Apoptosis
YopP/YopJ
Yersinia species
Cysteine protease, blocks MAPK and NFkappaB pathways
Apoptosis
58. Toxins injected into eukaryotic cells:
Inositol phosphate metabolism
SopB: in Salmonella is homologous to the Shigella flexneri
lpgD virulence factor.
Both proteins contain two regions of sequence similarities
with human inositol polyphosphatases types I and II.
60. Toxins injected into eukaryotic cells: Signal transduction
Toxin
Organism
Activity
Consequence
ExoS
P. aeruginosa
ADP-ribosylation of Ras, Rho GTPase
Collapse of cytoskeleton
C3 exotoxin
C. botulinum
ADP-ribosylation of Rho
Breakdown of cellular actin stress
fibers
ADP-ribosylation of Rho
Modification of actin cytoskeleton
Rac and Cdc42 activation
Membrane ruffling, cytoskeletal
reorganization, proinflammatory
cytokines production
EDIN-A, B and C S. aureus
SopE
S.
typhimurium
SipA
S.
typhimurium
Rac and Cdc42 activation
Membrane ruffling, cytoskeletal
reorganization, proinflammatory
cytokines production
IpaA
Shigella
species
Vinculin binding
Depolymerization of actin filaments
YopE
Yersinia
species
GAP activity towards RhoA, Rac1 or Cdc42
Cytotoxicity, actin depolymerization
YopT
Yersinia
species
Cysteine protease, cleaves RhoA, Rac, and
Cdc42 releasing them from the membrane
Disruption of actin cytoskeleton
VirA
Shigella
flexneri
Inhibition of tubulin polymerization
Microtubule destabilization and
membrane ruffling
61. Toxins injected into eukaryotic cells: Signal transduction
Toxin
Organism
Activity
Consequence
YpkA
Yersinia species
Protein serine/threonine kinase
Inhibition of phagocytosis
YopH
Yersinia species
Tyrosine phosphatase
Inhibition of phagocytosis
Tir
E. coli EPEC
Receptor for intimin
Actin nucleation and pedestalformation
CagA
H. pylori
Tyrosine phosphorylated
Cortactin dephosphorylation
YopM
Yersinia species
Interaction with PRK2 and RSK1 kinases
Cytotoxicity
SptP
S. typhimurium
Inhibition of the MAP kinase pathway
Enhancement of Salmonella capacity to
induce TNF-alpha secretion
ExoU
P. aeruginosa
Lysophospholipase A activity
Lung injury
62. Toxins with unknown mechanism of action
Toxin
Organism
Activity
Consequence
Zot
V. cholerae
?
Modification of intestinal tight junction
permeability
Hemolysin
BL (HBL)
B. cereus
Hemolytic, dermonecrotic and
vascular permeability activities
Food poisoning, fluid accumulation and
diarrhea
BSH
L. monocytogenes ?
Increased bacterial survival and intestinal
colonization
توکسین ها اولین فاکتور ویرولانت باکتریها بودن ک شناخته شدن و همچنین اولین عامل ارتباط بین بیولوژی سلولی و باکتری بودن ک شناخته شد.
حتی آغاز علم میکروبیولوژی هم با مطالعه توکسین ها اتفاق افتاده و تا همین اواخر هم به کمک تکنولوژی های جدید در حال گسترش ارتباطات بین باکتری و میزبانه.
Exotoxin: Easily inactivated by formaldehyde, iodine, and other chemicals to form immunogenic toxoids.
In the first example (figure 34.7a), the exotoxin is produced by bacteria growing in food. When food is consumed, the preformed exotoxin is also consumed. The classical example is staphylococcal food poisoning (see section 39.4) caused solely by the ingestion of preformed enterotoxin. Since the bacteria (Staphylococcus aureus) cannot colonize the gut, they pass through the body without producing any more exotoxin; thus, this type of bacterial disease is self-limiting.In the second example (figure 34.7b), bacteria colonize a mucosal surface but do not invade underlying tissue or enter the bloodstream. The toxin either causes disease locally or enters the bloodstream and is distributed systemically where it can cause disease at distant sites. The classical example here is the disease cholera caused by Vibrio cholerae (see section 39.4). Once the bacteria enter the body, they adhere to the intestinal mucosa where they are not invasive but secrete the cholera toxin, which is an AB exotoxin that catalyzes an ADP– ribosylation similar to that of diphtheria exotoxin (figure 34.5b). As a result, cholera toxin stimulates hypersecretion of water and chloride ions and the patient loses massive quantities of water.The third example of exotoxins in disease pathogenesis occurs when bacteria grow in a wound or abscess (figure 34.7c). The exotoxin causes local tissue damage or kills phagocytes that enter the infected area. A disease of this type is gas gangrene (see section 39.3) in which the exotoxin (-toxin) of Clostridium perfringens causes the tissue destruction in the wound.
Vasodilation:انبساطKupffer:Anatomy a phagocytic liver cell, involved in the breakdown of red blood cells.
نوروتوکسین ها عمدتاً بصورت پیشساز وارد دستگاه گوارش میشن و بعد از فعال شدن یا بطور مستقیم سیستم عصبیو تحت تاثیر قرار میدن، یا بطور غیر مستقیم با اثر روی سلول روده کوچیک باعث بروز علاعمی میشه. مثل انتروتوکسین B استاف اورئوس و توکسین باسیلول سرئوس و توکسین بوتولینوم. انتروتوکسین ها با اثر مستقیم روی مخاط، باعث افزایش ترشح میشن. توکسین کلرا ی نمونه کلاسیک این دسته توکسینهاست. دارای 5 زیر واحد B ک مثل لنگر به غشاء پلاسمایی سلول اپیتلیای متصل میشن و زیر واحد Aرو به داخل منتقل میکنن. سایتوتوکسین ها بطور اختصاصی روی سلول ها هدف عمل میکنن. به نسبت سلول هدف دارای اسم خاص هستن، مثل....معمولاً فعال سایتوتوکسیک وسیعی دارن و باعث مرگ بافت بصورتی ک دلیل اصلی اون مشخص نیست میشن. گاهی به اونا lecithinases یا phospholipasesهم گفته میشه. برخی از سایتوتوکسین ها ک باعث لیزشدن RBCها میشن hemolysinsنام دارن.
three groups of bacterial toxins.Group 1 toxins act either by binding receptors => sending a signal to the cell or by forming pores => perturbing the cell permeability barrier.Group 2 toxins are A/B toxins, binding domain (B subunit)enzymatically active (A subunit).Group 3 toxins are injected directly from the bacterium into the cell by a specialized secretion apparatus (type III or type IV secretion system).
Major histocompatibility complex (MHC) and the T-cell receptor variable domains of T-lymphocytes.اتصال غیرعادی سوپرآنتی ژن باعث میشه 2تا15 درصد سلولهای T فعال بشن. و درنتیجه تکثیر اونا زیاد میشه، سیتوکاینهای زیادی آزاد میشه و منجر به بروز اثرات سایتوتوکسیک میشه.
فقط چهار باکتری دارای سوپر آنتیژن هستن.عمدتاً توسط Staphylococcus and Streptococcus ترشح میشنMaM هم روی Tcellها اثر میزاره و باعش التهاب مزمن میشه و اثر ماتوژنیک و تحریک کننده تقسیم داره
sufficient concentration of an autoinducing peptide (AIPsufficient density of bacteriaAIP binds to transmembrane receptor AgrC outside the cell, turn phosphorylates AgrA, initiating transcription of the agr promoters.P2, which transcribes genes agrA, agrB, agrC, and agrD
بیماریزایی باکتریوئیدس فراژلیس بستگی به توکسین اون با نام فراژلین داره. این توکسین به گیرنده اختصاصی روی سلول اپیتلیال متصل میشه و باعث تحریک تقسیم سلول میشه.
همه دارای خاصیت متالوپروتئاز هستن
این دسته معمولاً در گرم مثبت ها دیده میشه و به توکسین های لایتیک هم مشهوره. با ایجاد حفره در غشائ پلاسمایی باعث خروج ملکول ها و ورود آب به سلول میشن. چون اکثراً از RBC ها برای تشخیص اونا استفاده میشه، به اونا همولایزین هم گفته میشه. ولی در شرایط واقعی همه ی سلولها از حساسیت یکسانی در برابر این توکسین ها برخوردارن.
این توکسین ها عمدتاً توسط گرم + ها ترشح میشن و حدود 20 نوع توکسین هستن. بطور اختصاصی به کلسترول متصل میشن. This class of cytolysins (Fig. 2, panel 2) comprises more than 20 family members, which are generally secreted bytaxonomically diverse species of Gram-positive bacteria and which have the common property of binding selectively tocholesterol on the eukaryotic cell membrane (Alouf and Geoffrey, 1991). Each toxin consists of a single 50- to 80-kDapolypeptide chain, and they are characterized by a pretty remarkable sequence similarity, also suggesting possible similar3D structures.
بطور انتخابی باعث خروج یا ورود مود کمتر از 2 کیلو دالتون میشن. عمدتاً توسط staphylococcal and streptococcal ترشح میشن. ابتدا بصورت یک زیرواحد محلول در آب ترشح میشن بصورت هپتامر درمیان.
بشترشون باعث تغییر نفوذپذیری غشا میشن ولی چندتاشونم باعث القای آپوپتوز در لمفوسیتها میشن.
RTXها توسط گرم منفی ها تولید میشن و بیش از 1000 نوع دارن ک داری انواعی از عملکردهاست.
این دسته دارای دوخصوصیت ویژه هستن: یکی اینکه دارای ی توالی خاص در انتهای خوشونن و اینکه توسط سیستم ترشحی نوع 1 ترشح میشن. نام RTX باین علت به اونا داده شده ک توالی C-terminal اونا دارای تعداد زیادی گلایسینه. این توالی
این توکسینا توسط چهار ژن ساخته میشن ک بخش HlyA دارای خاصیت همولیزینه. بقیه ژنها هم برای انجام تغغیرات پس از ترجمه لازمن.
دارای خاصیت دوقطبی مثل صابون هستن و بطور غیر اختصاصی به غشا متصل میشن. نحوه قرارگرفتنشون طوریه ک با غشا موازی هستن و در غشا ایجاد کانال نمیکنن. نفوذپذیری سلول هدف در ابتدا افزایش پیدا میکنه و نهایتاً در اثر تورم باعث لیزشدن و خروج محتویات سلول میشه. زیر واحد های توکسین در بافر آبی دارای شکل خاصی نیستن ولد در مایعات بدن دارای شکل هلیکس میشن.
یون کلسیم در فعالیت این توکسین ها نقش مهمی داره.
آئروتوکسین هم طی چند مرحله از حالت محلول در آب به شکلی درمیاد ک بتونه در غشا قرار بگیره.
دلتا توکسین استاف ک بصورت ی هلیکسه و کانالیو برای عبور یونها فراهم میکنه.
این توکسینا ک خاصیت حشره کشی دارن به دلتا توکسین ها مشهورن و تعدادی ازونا توسط Bacillus thuringiensis ترشح میشن. اثر این توکسین ها بصورت ایجاد منافذی در لوله گوارش حشرات پدیدار میشه.
بعضیاشون لیپید 2لایه رو تخریب میکنن و توکسینای B. Thuringiensis هم پتانسیل غشاییو تغییر میده.
عمدتاً دارای ساختار دوقسمتی هستن.
دامین A از لحاظ آنزیماتیک فعاله و مسئول شناخت ساختار هدف در سلول میزبانه. دامین B هم دارای ی ریسپتور غشاییه و مسئول انتقال زیرواحد A.
این توکسین ها قادرن در غلظت های پایین بسرعت باعث مرگ سلولی بشن. فعالیت این توکسین ها باعث غیر فعال شدن دائمی EF-2 میشه.
قدم مهمی در روشن شدن مکانیزم اثر این توکسین ها برداشته شد این بود ک تونستن ساختار 3بعدی توکسینو در حالی ک همراه NAD هستش، تشخیص بدن. و مشخص شد ک حضور NAD در ساختار توکسین اثر زیادی داره طوریکه اگر NAD همراه توکسین نباشه اصلاٌ توکسین قادر به تشخیص EF-2 نیست.
Signal transduction از مکانیزم های بسیار حیاطی برای زنده موندن هر سلوله. در سلولهای یوکاریوتی، پیامی ک به سطح سلول میرسه به دو روش به داخل منتقل میشه. ... ... تجمع این ترکیبات حد واسط باعث بهم خوردن مکانیسم های داخل سلول شده و منجر به مرگ میشود.
The A domain acts on eukaryotic cells by ADP-ribosylating their GTP-binding proteinsThe B domain is a nontoxic oligomer that binds the receptors on the surface of eukaryotic cells and allows the toxicsubunit S1 to reach its intracellular target proteinsrole of many residues of S1 has been tested by site-directed mutagenesis to produce nontoxic mutants of the toxin to be used as vaccines.
A mRNA molecule is said to be monocistronic when it contains the genetic information to translate only a single protein chain (polypeptide). CT کلرا و توکسین LT ایکولای از لحاظ ساختاری و عملکرد بسیار شبیه هم هستن. CT در محیط کشت پخش میشه ولی توکسین LT در غشا خارجی و متصل به LPS باقی میمونه. ژن توکسین CT بوسیله و فاژ فیلامنتوس منتقل میشه ولی ژن توکسین LT روی پلاسمید قرار داره.
انتروتوکسین A کلستریدیوم دیفیسیل و سایتو توکسین B اون، در ایجاد اسهال آنتی بیوتیکی نقش زیادی دارن. ژنهای این توکسین ها در لوکوس PaLoc است که حاوی ژنهای اصلی A و B، و ژنهای کمکی C-D است.
آلفا توکسین مهمترین توکسین کلستریدیوم پرفرینجنس هست و باعث بروز گانگرن میشه. این توکسی در انتشار باکتری نقش مهمی داره. باعث سرکوب ایمنی میزبان و تحریک واکنش های التهابی و تغییر در غلظت کلسیم داخل سلولی میشه. Cel Division Cycle Human CDC42 is a small GTPase of the Rho-subfamily, which regulates signaling pathways that control diverse cellular functions including cell morphology, migration, endocytosis and cell cycle progression.
Stress fibers are high order structures in non-muscle cells which consist of actin filaments, crosslinking proteins, and myosin II motors. stress fibers have since been shown to play an important role in cell motility and, providing force for a number of cell functions such as cell adhesionand morphogenesis.[2]
فعالیت اسکلت سلولی توسط پروتئین های G کنترل میشه. Cdc42 ملکولهایی هستن ک کنترل شکل سلولو به عهده دارن. The Ras family is generally responsible for cell proliferation, Rho for cell morphology,
لیمفوستاتین، پروتئینیه ک توسط ایکولای ترشح میشه و بتازگی کشف شده. نقش توکسینی داره و بطور انتخابی تولید انترلوکین های 2 و4 و 5 و اینترفرون گامارو متوقف میکنه، در نتیجه تکثیر سلول های ایمنی متوقف میشه و در ایمنی اختلال ایجاد میشه.
iota-like toxins:C. perfringens iota toxin and C. spiroforme and C. difficile ADP-ribosylating toxins
وزیکول ها از ساختارهای ضروری در فرایند هایی مثل اندوسیتوز به واسطه ریسپتور و اگزوسیتوز هستن. وزیکول ها عمدتاً در شبکه آندوپلاسمی ساخته میشن و پس از تغییراتی در گلژی به سطح سلول میرن.یک نمونه از کاربرد اگزوسیتوز در تنزیم فرایندهای بدن، نقش اون در رهاسازی نوروترنسمیترهاست.
Synaptosomal-associated protein 25 (SNAP-25)SNARE:SNAP REceptorAcetylcholine & neurotransmiters
Vesicle associated membrane proteins (VAMP) are a family of SNARE proteins with similar structure, and are mostly involved in vesicle fusion.
سلولهای میزبانو بصورت تکی مورد هدف قرار میده و با سیستم ترشحی وابسته به اتصال، توکسین به سیتوپلاسم سلول هدف منتقل میشه. This definition failed to explain the pathogenicity of many virulent bacteria such as Salmonella, Shigella and Yersinia, which did not release toxic proteins into the culture supernatant.
فقط شیگلا هایی ک موفق به ترک فاگوزوم میشن میتونن توی میزبان خودشون، آپوپتوز الغا کنن. Ipa توسط سیستم ترشحی نوع 3 به خارج شیگلا فرستاده میشه و بیان ژنهای زیرمجموعه آغاز میشه. بین این زیر واحدها، وجود زیرواحد IpaB برای شروع الغای مرگ سلولی ضروریه. این مکلول روی interleukin-1β ک یکی از افکتورهای مرگ سلولیه اثر میزاره و زمینه گسترش باکتری فراهم میشه.
مشابه اینویزین شیگلاست و برعکس شیگلا ، سالمونلا از فاگوزوم فرار نمیکنه و داخل فاگوزوم زنده میمونه و تکثیر میکنه.
ICE: Caspase 1/interleukin-1 converting enzymeis an enzyme that proteolytically cleaves other proteins, such as the precursor forms of the inflammatory cytokinesinterleukin 1-β and interleukin 18, into active mature peptides.Mitogen-activated protein kinases are involved in directing cellular responses to a diverse array of stimuli, such as mitogens, osmotic stress, heat shock.NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) is a protein complex that controls the transcription of DNA. NF-κB is found in almost all animal cell types and is involved in cellular responses to stimuli such as stress, cytokines, free radicals, ultraviolet irradiation, oxidized LDL, and bacterial or viral antigens
اگزوتوکسینS سودوموناس آئروژینوزا ی توکسینه بادو عملکرد. ADP-ribosyltransferase در دامین سی ترمینال این توکسین قرار داره و بتازگی مسخص شده ک توالی واقع در اِن ترمینال این توکسین باعث گردشدن میزبان میشه. In mammalian cells, vinculin is a membrane-cytoskeletal protein in focal adhesion plaques that is involved in linkage of integrin adhesion molecules to the actin cytoskeleton.