752-

4001

-00

VM

ikro

biol

ogie

Lect

ure

Hum

an -

Mic

robe

Inte

ract

ion

Dec

embe

r 3M

arku

s S

chup

pler

Con

tent

base

d on

Bro

ck 1

3/E

, Cha

pter

27:

Mic

robi

al In

tera

ctio

ns w

ith H

uman

s

•Wha

t is

norm

al m

icro

flora

ass

ocia

ted

with

var

ious

bod

y si

tes?

–sk

in–

oral

cav

ity–

gast

roin

test

inal

trac

t–

resp

irato

ry tr

act

–ur

ogen

ital t

ract

•How

are

bac

teria

l inf

ectio

ns tr

ansm

itted

?

•Wha

t are

the

mec

hani

sms

of p

atho

gene

sis?

•How

to m

easu

re v

irule

nce?

•Wha

t are

bac

teria

l viru

lenc

e fa

ctor

s?

•Wha

t are

the

maj

or ty

pes

of b

acte

rial t

oxin

s an

d ho

w d

o th

ey w

ork?

Def

initi

ons

•N

orm

al fl

ora:

mix

ture

of m

icro

orga

nism

s us

ually

foun

d at

any

anat

omic

al s

ite in

a h

ealth

y or

gani

sm

•Pa

rasi

te:

an o

rgan

ism

that

gro

ws

in o

r on

a ho

st

caus

ing

dam

age

•Pa

thog

en:

a m

icro

bial

par

asite

that

har

ms

mic

robi

al h

ost

•Pa

thog

enic

ity:

abili

ty to

pro

duce

dis

ease

or d

amag

e to

hos

t

•Vi

rule

nce:

quan

titat

ive

mea

sure

of p

atho

geni

city

•In

fect

ion:

colo

niza

tion

and

grow

th o

f mic

robe

s in

hos

t

•D

isea

se:

inju

ry o

r dam

age

of th

e ho

st

¾In

fect

ion�

Dis

ease

Can

ani

mal

s be

free

of m

icro

orga

nism

s?¾

Gno

tobi

otic

-de

scrib

es th

e co

nditi

on o

f ger

m-fr

ee in

ani

mal

s

¾G

noto

biot

ic a

nim

als

-mam

mal

s>

unbo

rn o

ffspr

ing

is re

mov

ed a

sept

ical

ly fr

om th

e st

erile

wom

b-b

irds

> ca

refu

l ste

riliz

atio

n of

the

exte

rior o

f the

egg

The

germ

-free

ani

mal

s w

ere

then

rear

ed in

a g

erm

-free

env

ironm

ent

¾C

hara

cter

istic

s of

gno

tobi

otic

ani

mal

s

> ab

norm

al a

nato

mic

al a

nd p

hysi

olog

ical

feat

ures

-und

erde

velo

ped

lym

phat

ic ti

ssue

-t

hin

inte

stin

al w

all

-low

ant

ibod

y tit

er

> hi

gher

sus

cept

ibili

ty to

pat

hoge

ns>

requ

ire n

utrit

iona

l sup

plem

ents

that

are

nor

mal

ly p

rovi

ded

by n

orm

al fl

ora

> re

duce

d su

scep

tibili

ty to

cer

tain

dis

ease

pro

cess

es d

epen

dent

on

mic

robe

se.

g. n

o de

ntal

car

ies

or p

laqu

e fo

rmat

ion

Nor

mal

flor

a¾

Ani

mal

s pr

ovid

e fa

vora

ble

envi

ronm

ents

for g

row

th o

f mic

robe

s-o

rgan

ic n

utrie

nts

and

grow

th fa

ctor

s-r

elat

ivel

y co

nsta

nt c

ondi

tions

: e.g

. pH

, osm

otic

pre

ssur

e, te

mpe

ratu

re

and

regi

ons

or o

rgan

s sh

owin

g se

lect

ive

cond

ition

s-d

ry o

r wet

(s

kin

vs.

mou

th)

-aer

obic

or a

naer

obic

(lu

ngs

vs.

gas

troin

test

inal

trac

t)-p

H

(ora

l cav

ity v

s. s

tom

ach)

¾M

ost c

omm

on s

ites

for c

olon

izat

ion:

muc

ous

mem

bran

es-r

espi

rato

ry-,

gast

roin

test

inal

-, ur

inar

y tra

ct-l

ined

with

laye

r(s)

of e

pith

elia

l cel

ls-c

oate

d w

ith la

yer o

f muc

us-d

iffer

ent t

ypes

of i

nter

actio

ns

¾N

orm

al fl

ora

prot

ects

the

host

from

col

oniz

atio

n by

pat

hoge

nic

mic

robe

s(>

bact

eria

l int

erfe

renc

e)ho

wev

eral

so n

orm

al m

icro

bes

may

bec

ome

path

ogen

ic(c

ompr

omis

ed h

ost)

Tabl

e 27

.1

Nor

mal

flor

a: S

kin

abou

t 2 m

2 of

ski

n su

rfac

e

¾un

favo

rabl

e ha

bita

t for

m

icro

orga

nism

s-m

ost a

reas

sub

ject

to p

erio

dic

dryi

ng-s

light

ly a

cidi

c pH

-hig

h so

dium

chl

orid

e co

ncen

tratio

n-1

00 to

10.

000

bact

eria

per

cm

2dr

y sk

in

¾m

ost s

kin

mic

robe

s ar

e as

soci

ated

with

sw

eat g

land

s (s

ecre

tions

con

tain

wat

er, a

min

o ac

ids,

ure

a, s

alts

and

fatty

aci

ds)

-ecc

rine

glan

dsdi

sper

sed

swea

t gla

nds

-apo

crin

e gl

ands

activ

ated

dur

ing

pube

rty: u

nder

arm

, gen

ital a

rea

etc.

> un

dera

rm o

dor d

ue to

bac

teria

l act

ivity

-seb

aceo

us g

land

s>

asso

ciat

ed w

ith h

air f

ollic

le

¾no

rmal

flor

a:S

taph

yloc

occu

s, C

oryn

ebac

teriu

m, A

cine

toba

cter

,M

icro

cocc

us, P

ropi

onib

acte

rium

, P

ityro

spor

um (y

east

)

Figu

re 2

7.2

Nor

mal

flor

a: O

ral C

avity

¾co

mpl

ex a

nd h

eter

ogen

eous

m

icro

bial

hab

itat

¾in

gest

ed fo

od a

s so

urce

of

nut

rient

s

¾to

oth

min

eral

mat

rix o

f ca

lciu

m p

hosp

hate

(ena

mel

)

¾sa

liva

(sal

ts, e

nzym

es, m

ucop

rote

ins

etc.

)

lact

oper

oxid

ase:

nat

ural

ant

ibio

tic(g

ener

ates

sin

glet

oxy

gen)

lyso

zym

e: c

leav

es g

lyco

sidi

clin

kage

s of

pep

tidog

lyca

n

lact

ofer

rin: i

ron-

bind

ing

prot

ein

(dep

rives

bac

teria

an

elem

ent

nece

ssar

y fo

r gro

wth

)Fi

gure

27.

4

Den

tal P

laqu

e¾

atta

chm

ent o

f aci

dic

glyc

opro

tein

s fr

om s

aliv

a le

ads

to th

in o

rgan

ic fi

lm

¾co

loni

zatio

n of

sm

ooth

toot

h su

rfac

edu

e to

affi

nity

to g

lyco

prot

eins

¾on

ly fe

w S

trep

toco

ccus

spp.

S. s

angu

is, S

. sob

rinus

, S. m

utan

s, S

. miti

s

S. m

utan

s pr

oduc

es d

extra

n fro

m s

ucro

se>

prod

uctio

n of

bio

film

(pla

que)

> su

bseq

uent

est

ablis

hmen

t of

-fila

men

tous

Fus

obac

teriu

msp

p.-S

piro

chet

es-g

ram

-pos

itive

rods

-gra

m-n

egat

ive

cocc

i-A

ctin

omyc

essp

p.Fi

gure

27.

6

Taub

man

Nat

ure

Rev

iew

s Im

mun

olog

y6,

555

-563

(Jul

y 20

06) |

doi

:10.

1038

/nri1

857

Mut

ans

stre

ptoc

occi

par

ticip

ate

in th

e fo

rmat

ion

of p

laqu

e on

toot

h su

rfac

es

a In

itial

atta

chm

ent o

f mut

ans

stre

ptoc

occi

to

toot

h su

rface

s as

the

first

eve

nt in

the

form

atio

n of

den

tal p

laqu

e

b A

ccum

ulat

ion

of m

utan

sst

rept

ococ

ci o

n to

oth

surfa

ce in

the

pres

ence

of s

ucro

se

c A

cid

prod

uctio

n by

mut

ans

stre

ptoc

occi

¾Th

e m

etab

olis

m o

f var

ious

sac

char

ides

(in

clud

ing

gluc

ose

and

fruct

ose)

by

the

accu

mul

ated

bac

teria

l bio

film

resu

lts in

the

prod

uctio

n an

d se

cret

ion

of c

onsi

dera

ble

amou

nts

of th

e m

etab

olic

end

-pro

duct

lact

ic

acid

, whi

ch c

an c

ause

dem

iner

aliz

atio

n of

th

e to

oth

stru

ctur

e w

hen

pres

ent i

n su

ffici

ent

amou

nts

in c

lose

pro

xim

ity to

the

toot

h su

rface

.

Den

tal C

arie

s¾

infe

ctio

us d

isea

se c

ause

d by

mic

roor

gani

sms

in p

laqu

e!

¾fe

rmen

tatio

n of

sug

ars

to la

ctic

aci

d by

lact

ic a

cid

bact

eria

> de

calc

ifica

tion

of th

e en

amel

of t

he to

oth

¾di

rect

cor

rela

tion

betw

een

S. m

utan

san

d de

ntal

car

ies

> 80

-90

% o

f all

peop

le in

US

and

Wes

tern

Eur

ope

> ne

arly

abs

ent i

n Ta

nzan

ian

child

ren

> pr

esum

ably

bec

ause

suc

rose

is a

bsen

t

NIS

HIH

AR

A&

KO

SE

KI P

erio

dont

olog

y200

0, V

ol. 3

6, 2

004,

14–

26 2

004

Gin

givi

tis a

nd P

erio

dont

itis

¾in

fect

ion

of th

e gi

ngiv

al c

revi

ce

(per

iodo

ntal

poc

ket)

¾se

vera

l “m

arke

r bac

teria

“ -A

ctin

obac

illus

act

inom

ycet

emco

mita

ns-P

orph

yrom

onas

gin

giva

lis-P

revo

tella

inte

rmed

ia-B

acte

roid

es fo

rsyt

hus

-Tre

pone

ma

dent

icol

a

¾G

ingi

vitis

>

infla

mm

atio

n of

the

gum

s du

e to

pla

que

alon

g th

e gu

mlin

e

¾Pe

riodo

ntiti

s

> lo

ssof

col

lage

n at

tach

men

t of t

he to

oth

to th

e bo

ne>

form

atio

n of

dee

p pe

riodo

ntal

poc

kets

>

bone

des

truct

ion

Bac

teria

l int

erac

tions

with

muc

ous

mem

bran

es

loos

e A

ssoc

iatio

n

Adh

esio

nIn

vasi

on to

sub

muc

osal

epith

elia

l cel

ls

Figu

re 2

7.1

Nor

mal

flor

a: G

astro

inte

stin

al T

ract

Figu

re 2

7.9

Nor

mal

flor

a: G

astro

inte

stin

al T

ract

Figu

re 2

7.9

Stom

ach

-dig

estio

n of

mac

rom

olec

ules

-sec

retio

n of

aci

d >

pH 2

-c

hem

ical

bar

rier f

or b

acte

ria

> de

void

of n

orm

al fl

ora?

Hel

icob

acte

r pyl

ori

> co

loni

zatio

n of

the

gast

ric

non-

acid

-sec

retin

g m

ucos

a-h

ydro

lyze

s ur

ea

(diff

usin

g fro

m b

lood

) >

incr

ease

in p

H-b

uffe

red

zone

aro

und

the

cells

allo

ws

colo

niza

tion

-inf

lam

mat

ion,

tiss

ue

dest

ruct

ion

and

ulce

ratio

n

Nor

mal

flor

a: G

astro

inte

stin

al T

ract

Smal

l int

estin

e¾

pH 4

-5¾

cont

inue

d di

gest

ion:

abso

rptio

n of

mon

osac

char

ides

, am

ino

acid

s, fa

tty a

cids

, wat

er

¾D

uode

num

and

Jej

unum

ar

e al

mos

t ste

rile

¾Ile

um: 1

05–

107

cells

ml-1

Larg

e in

test

ine

¾fe

rmen

tatio

n ch

ambe

r¾

1010

-101

2ce

lls g

-1

-foo

d pa

ssag

e tim

e ab

out 2

4h-g

row

th ra

te o

f lum

inal

bac

teria

:1

-2 d

oubl

ings

per

day

¾ch

emos

tate

-like

beh

avio

r due

to

con

stan

t los

s of

mat

eria

lFi

gure

27.

9

Effe

cts

of G

astro

inte

stin

al F

lora

¾be

nefic

ial e

ffect

s of

inte

stin

al m

icro

bes

> pr

ofou

nd in

fluen

ce o

n ho

st fu

nctio

n an

d w

ell-b

eing

!

-vita

min

syn

thes

is:

B12

, K, p

yrid

oxin

e, ri

bofla

vin,

thia

min

-glu

cosi

dase

act

ivity

: m

any

suga

r fer

men

ting

bact

eria

-ste

roid

met

abol

ism

:m

odifi

catio

n of

bile

aci

ds-S

CFA

pro

duct

ion:

ac

etic

, pro

pion

ic, b

utyr

ic a

cids

are

(sho

rt-ch

ain

fatty

aci

ds)

abso

rbed

and

util

ized

by

the

host

stim

ulat

e co

loni

c ep

ithel

ial c

ell p

rolif

erat

ion

¾ga

s pr

oduc

tion

(flat

us):

CO

2, H

2, C

H4

(in a

bout

1/3

of p

eopl

e)se

vera

l hun

dred

ml/d

also

N2

from

sw

allo

wed

air

¾od

orpr

oduc

tion:

H2S

, NH

3, am

ines

, ind

ole,

ska

tole

, bu

tyric

aci

d

¾in

fluen

ce o

f ant

ibio

tics

> ki

ll pa

thog

ens

buta

lso

heal

thy

mic

robe

s>

lead

s to

gas

tric

dist

ress

unt

il no

rmal

flor

a be

com

es re

esta

blis

hed

Nor

mal

flor

a: R

espi

rato

ry T

ract

¾M

ajor

sec

tions

uppe

r res

pira

tory

trac

t-S

trept

ococ

ci, S

taph

yloc

occi

, G

ram

-neg

ativ

e co

cci

-als

o pa

thog

ens:

S

trept

ococ

cus

pyog

enes

, S

trept

ococ

cus

pneu

mon

iae

Sta

phyl

ococ

cus

aure

us,

Cor

yneb

acte

rium

dip

hthe

riae

low

er re

spira

tory

trac

t-e

ssen

tially

ste

rile

¾M

odes

of p

rote

ctio

n-c

ontin

uous

upw

ard

stre

am o

f flo

win

g m

ucus

pro

duce

d by

cili

ated

cel

ls-p

rodu

ctio

n of

lyso

zym

e in

muc

us

-pha

gocy

tic a

ctio

n of

mac

roph

ages

-res

iden

t flo

ra li

mits

gro

wth

of p

atho

gens

Figu

re 2

7.11

Nor

mal

flor

a: U

roge

nita

l Tra

ct¾

Bla

dder

itse

lf us

ually

ste

rile

¾U

reth

ra>

epith

eliu

m c

olon

ized

by

facu

ltativ

e ae

robi

c gr

am-n

egat

ive

rods

and

coc

ci

-con

tain

s al

so o

ppor

tuni

stic

pat

hoge

ns: E

sche

richi

a co

li, P

rote

us m

irabi

liset

c.

-may

bec

ome

path

ogen

e.g

. due

to lo

cal c

hang

es in

pH

-b

acte

ria m

ultip

ly a

nd fr

eque

ntly

cau

se u

rinar

y in

fect

ions

¾Va

gina

adul

tsco

ntai

ns s

igni

fican

t am

ount

s of

gly

coge

n fe

rmen

ted

by L

acto

baci

llus

acid

ophi

lus

prod

uctio

n of

lact

ic a

cid Ļ

pH

befo

re p

uber

tyno

gly

coge

n sy

nthe

size

d,

no b

acte

rial n

utrit

ion

sour

ce, Ĺ

pH

afte

r men

opau

sere

turn

to g

lyco

gen-

free,

alk

alin

e en

viro

nmen

t lac

king

lact

ic a

cid

bact

eria

Doe

derle

in‘s

baci

llus

Figu

re 2

7.12

b

Viru

lenc

e¾

Abi

lity

to c

ause

dis

ease

thro

ugh

toxi

city

or i

nvas

iven

ess

¾To

xici

ty>

dise

ase

caus

ed b

y a

pref

orm

ed to

xin

that

inhi

bits

hos

t cel

l fun

ctio

n or

kill

s ho

st c

ells

-E

xoto

xins

(in

clud

ing

ente

roto

xins

)-E

ndot

oxin

� E

nter

otox

in!

¾In

vasi

vene

ss>

abili

ty to

mul

tiply

in ti

ssue

in s

uch

larg

e nu

mbe

rs th

at h

ost f

unct

ion

is in

hibi

ted

(e.g

. Stre

ptoc

occu

s pn

eum

onia

e)

Add

ition

al fe

atur

es-v

irule

nce

gene

s ar

e of

ten

clus

tere

d in

“pat

hoge

nici

ty is

land

s”-p

atho

geni

city

isla

nds

are

abse

nt in

clo

sely

rela

ted

aviru

lent

stra

ins

-man

y ba

cter

ial p

atho

gens

als

o ca

rry

viru

lenc

e ge

nes

on la

rge

plas

mid

s

How

to m

easu

re V

irule

nce?

¾Vi

rule

nce

can

be e

stim

ated

from

stu

dies

of t

he L

D50

(leth

al d

ose 5

0)

Atte

nuat

ion

> de

crea

se o

r los

sof

viru

lenc

e af

ter

labo

rato

ry c

ultu

re>

atte

nuat

ed s

train

sw

ere

ofte

n us

ed fo

r pr

oduc

tion

of v

acci

nes Fi

gure

27.

14

Wha

t are

bac

teria

l Viru

lenc

e Fa

ctor

s?¾

fact

ors

that

pro

mot

e pa

thog

enes

is:

e.g

. Sal

mon

ella

P. 8

38 F

igur

e 2

Wha

t are

the

Mec

hani

sms

of P

atho

gene

sis?

Whi

ch fa

ctor

s ar

e re

spon

sibl

e fo

r the

en

try o

f a p

atho

gen

into

hos

t?

¾Pa

thog

en m

ust h

ave

acce

ss

to h

ost t

issu

e an

d m

ultip

ly

> pe

netr

atio

n of

ski

n,

muc

ous

mem

bran

es,

inte

stin

al e

pith

eliu

mw

hich

act

as

barr

iers

Figu

re 2

7.13

Non

spec

ific

inna

te re

sist

ance

to in

fect

ion

¾A

ge, s

tres

s an

d di

etaf

fect

ove

rall

heal

th a

nd th

eref

ore

host

resi

stan

ce to

infe

ctio

ns>

YO

PI‘s

: you

ng, o

ld, p

regn

ant,

imm

uno-

com

prom

ised

peo

ple

¾Ph

ysic

al, c

hem

ical

and

ana

tom

ical

bar

riers

epid

erm

is, m

ucus

, ant

i-mic

robi

al c

ompo

unds

, low

pH

, nor

mal

flor

a

¾Ti

ssue

spe

cific

itypa

thog

ens

only

mul

tiply

in c

erta

in ti

ssue

¾C

ompr

omis

ed h

ost

> no

pro

per f

unct

ion

of o

ne o

r mor

e of

resi

stan

ce m

echa

nism

s du

e to

-illn

ess

-dru

g th

erap

y-i

njur

y-A

IDS

> co

mpr

omis

ed h

ost i

s of

ten

enco

unte

red

in a

hos

pita

l situ

atio

n:-p

roxi

mity

to d

isea

se c

arrie

rs-i

nvas

ive

proc

edur

es-n

osoc

omia

l inf

ectio

ns (i

nfec

tions

that

occ

ur in

a h

ospi

tal s

ettin

g)

Mai

n Ty

pes

of b

acte

rial E

xoto

xins

I

1.C

ytol

ytic

exo

toxi

ns:

> ac

t on

cyto

plas

mic

mem

bran

e ca

usin

g ce

ll ly

sis

Hem

olys

ins

wor

k on

var

ious

cel

ls

test

ed o

n R

BC

Leci

thin

ases

&at

tack

CM

pho

spho

lipid

s P

hosp

holip

ases

(pho

spha

tidyl

chol

ine)

Leuc

ocid

ins

wor

k on

leuk

ocyt

es

2.A

-B to

xins

: >

con

sist

of t

wo

subu

nits

A&

Bon

e bi

nds

to h

ost r

ecep

tor

seco

nd e

nter

s an

d da

mag

es th

e ce

ll

Bot

ulin

um to

xin

Clo

strid

ium

bot

ulin

umC

hole

ra to

xin

Vib

rio c

hole

rae

Dip

hthe

ria to

xin

Cor

yneb

acte

rium

dip

hthe

riae

Teta

nus

toxi

nC

lost

ridiu

m te

tani

3.Su

pera

ntig

ens:

> st

imul

ate

host

T c

ells

and

lead

to e

xten

sive

infla

mm

ator

y re

spon

se

e.g.

Sta

phyl

ococ

cus

aure

us fo

od p

oiso

ning

Stap

hylo

cocc

al E

nter

otox

ins

A -

E(in

75%

of c

ases

SE

A)

> pr

oduc

ed d

urin

g gr

owth

of S

.aur

eus

in fo

od

> he

at re

sist

ant (

10 m

in 1

00°C

)>

cook

ing

inac

tivat

es b

acte

ria b

ut n

otth

e en

tero

toxi

ns

Mod

e of

act

ion

> en

tero

toxi

ns b

ind

to T

cel

l rec

epto

r ȕ c

hain

s >

stim

ulat

e T

help

er c

ells

to c

ytok

ine

prod

uctio

n >

over

abun

danc

e of

IL-2

resp

onsi

ble

for m

ost s

ympt

oms

of g

astro

ente

ritis

Gas

troe

nter

itis

> sy

mpt

oms

deve

lop

with

in 1

to 6

hou

rs a

nd la

st 2

4 to

48

hour

s>

naus

ea, v

omiti

ng, s

ever

e ab

dom

inal

cra

mps

, dia

rrhe

a, h

eada

che

> se

lf-lim

ittin

g, m

orta

lity

rate

ver

y lo

w to

nil

Mai

n Ty

pes

of b

acte

rial E

xoto

xins

II

Ove

rvie

w o

f Im

mun

e R

espo

nse

to P

atho

gens

1

nons

peci

fic im

mun

ity

2

antib

ody-

med

iate

d im

mun

ity

3

cell-

med

iate

d im

mun

ity

Figu

re 2

9.5

from

Bro

ck 1

2/E

IL-1

IL-2

IFN-DŽ

TNF-Į

0.01

–0.

1 %

of T

-cel

l pop

ulat

ion

5 -3

0 %

of T

-cel

l pop

ulat

ion

How

do

Sup

eran

tigen

s w

ork?

A-B

Tox

ins:

Cho

lera

Tox

in

-A-B

type

toxi

n ex

erts

its

effe

ct in

sm

all i

ntes

tine

-B fr

agm

ent c

onta

ins

bind

ing

site

-A

frag

men

t act

ivat

es a

deny

l cyc

lase

(ĹcA

MP

)-c

AM

P s

timul

ates

exc

retio

n of

Cl-

and

HC

O3-

¾m

assi

ve lo

ss o

f wat

er fr

om d

iarr

hea

may

be

fata

l due

to d

ehyd

ratio

n! Figu

re 2

7.24

A-B

Tox

ins:

Bot

ulin

us T

oxin

•B

otox

= B

otul

inum

Neu

roto

xin

(BoN

T)

•se

ries

of s

even

rela

ted

A-B

toxi

ns

(two

enco

ded

on a

lyso

geni

c ph

age)

•pr

oduc

edby

Gra

m-p

ositi

ve a

naer

obic

Clo

strid

ium

botu

linum

•fo

und

in u

npro

perly

cann

ed fo

od

(end

ospo

res

germ

inat

e >

anae

robi

c gr

owth

)

•in

toxi

catio

nÆ

Bot

ulis

m

•S

ympt

oms:

cum

ulat

ive,

flac

cid

para

lysi

s (e

yes,

tong

ue, l

imbs

, res

pira

tory

arr

est)

•Le

thal

ora

l dos

e: 5

0-70ȝg

per

per

son

Æm

ostt

oxic

subs

tanc

ekn

own

1 m

g w

ould

be

suffi

cien

t to

kill

1 M

illio

n gu

inea

pig

s!

A-B

Tox

ins:

Bot

ulin

us T

oxin

BoN

T pr

even

ts re

leas

e of

ace

tylc

holin

e at

pre

-syn

aptic

mot

or n

euro

n en

d pl

ate

¾fla

ccid

par

alys

is

Figu

re 2

7.22

A-B

Tox

ins:

Te

tanu

s To

xin

-C

lost

ridiu

m te

tani

infe

ctio

n of

dee

p w

ound

s-

bind

s to

inhi

bito

ry in

tern

euro

ns a

nd b

lock

s re

leas

e of

gly

cine

-pr

even

ts re

laxa

tion

of m

uscl

e

¾sp

astic

par

alys

is

Figu

re 2

7.23