MICRB 412 Lecture 4: Bacterial Toxins

what were the first virulence factors identified?

toxic proteins (toxins)

why were toxic proteins (toxins) the first virulence factors identified?
how? (4)

because they are easy to isolate and identify.
how:
-Usually released or excreted outside cell
-Are either proteins or small molecules.
-Have clear, measurable effects.
-Can determine specific targets.

toxic proteins--why in bacteria?
6 reasons

origin of toxins
where are they NOT normally?
where can they be found? how?
OR where else can they be found?
how they are gained
Implications? (2)

note on 1: allow proliferation of both or provide advantage to one or the other

endotoxin
def
loc
released how?

small, lipid-like compounds (just an essential part of a g neg or go pos cell mem)
Embedded in the bacterial membrane
Released by cell lysis

exotoxin
def

protein excreted by the cell (made specifically to be a toxin)

how are toxins named? (2)
2 ex of first

Named for cell or tissue type which is attacked
-Cytotoxin: attack various cell types
-Specific: neurotoxin, leukotoxin, hepatotoxin, cardiotoxin, enterotoxin, verotoxin (kidney cells of african green monkey)
named for species origin: Cholera, Diphtheria

heat-labile or heat stable toxins
why?

if heat inactivated = protein = exotoxins (denature w heat then cool, form crosslinks, fold improperly)

non-protein toxins
usually what type of toxin?
major endotoxin in g neg cells
what is the immunogenic part?

LPS and TLR 4
when do we have LPS in our body?
what is released? (2)
what is promoted?
what this leads to?
results in what? (2)
what is activated and what does this cause
end result

we only have LPS in our body when an infection is present

why might tx w antibiotics be bad?

cell will be destroyed and release toxins

non-protein toxins
major endotoxin in g pos cells
how its released
what it promotes
what else it promotes
what it binds to
what its involved in

pertussis (whooping cough) blebs
toxin involved and what it does

tearing of lungs and therefore inc proliferation of bac

exotoxins
types and what they do

type I exotoxins
aka
what they can cause
what theyre prod by
what were cases linked to?
what spread? what didnt?

type I mechanism
Normal

type I mechanism
when superantigen

type II mechanism
general class of what
2 general steps
often named what??
why rbcs?

why RBCs?--acquire iron and other nutrients abundant in RBCs

type II-Phospholipases
what will they remove? why?
other phospholipases cleave where?

C. perfringens
what does it cause?
what type of toxin is it?
what does it do? what is the tx?
what happens if it spreads to blood?

type II--pore forming toxins
what do toxins interact w?
where are the toxins inserted?
what happens w assembly of proteins?
what does acidic pH do?
where is low pH found?
what does pore allow for?
end result?

type II--pore forming toxins
2 types
2 specific exs.

hemolysin--S. aureus
5 steps
what leads to pore formation?

type II--pore forming toxins overview

Type III--A-B toxins
a portion
-what it does
-what it needs to kill cells
-where does it become active
b portion
-fn
-what its usually made of
can be produced ___ or ____

A-B Toxins come in many flavors

type III-A-B toxins
endosomes and retrograde transport

Type III - A-B Toxins
type of toxin, molecular organization, and translocation:
dipthereia, botulinum, tetanus
antrax, C2
cholera, shiga(like), heat-labile
exotoxin A, ricin

Type III - A-B Toxins
ADP ribosylation in diphtheria and cholera toxin
and effect of each

Type III - A-B Toxins
Not all A portions are ADP-ribosyltransferases Many are - what does that tell us??????
shiga toxin:
-what it cleaves
-what this results in
botulinum toxin:
-what this cleaves
-where are these found?
-stops release of what?
-which sto

Botulism - botulinum toxin (BoTox)
top 5 highest risk what?
how much can paralyze the chest muscles of 1 million ppl?
what does tx do?
what does it NOT kill? what does this mean?
how long can recovery be?

Botulism - botulinum toxin (BoTox)
how is it different from other toxins?
where is it highly prevalent?
normally, that bacteria cant do what?
-therefore it cant...
-where it grows best
what can be a carrier?

Botulism - botulinum toxin (BoTox)
what is its str?
heavy chain fn
light chain fn
what is this, essentially?
end result

botox

Botulism - botulinum toxin (BoTox)

Antitoxins, Toxoids and vaccines
antitoxin
-b portion
-abs to what portion?

a "future pharmacy

Antitoxins, Toxoids and vaccines
toxoid
-how to render non toxic
-then what do you do w it
vaccine
-now can do what
what can C. diptheriae and other bac still do? but what can they NOT do?

Yersinia pestis
what does it cause?
what type of toxin is it?
before and after injection

Yersinia pestis (Bubonic plague)
three documented human plague pandemics

Early divergent strains of Yersinia pestis in Eurasia 5000 years ago
how was it identified?
what was identified?
therefore, the infection was what