Bacterial Toxins (23)

Front 1

saprophytes

Back 1

-not associated with disease
-free living bacteria
-most Bacillus spp.

Front 2

commencials

Back 2

-live in association w a host, relationship benefits both
-staphylococcus

Front 3

opportunistic pathogens

Back 3

-cause disease in compromised hosts
-pseudomonas, staphylococcus

Front 4

pathogen

Back 4

-capable of causing disease in a "normal" host
-Bacillus anthrasis, corynebacterium diptheriae

Front 5

virulence

Back 5

-degree of pathogenicity
-based upon ability to produce virulence factors
-also dependent on portal of entry and presence/absence of normal flora

Front 6

Properties of a pathogen (4)

Back 6

1) gain access to host (correct portal of entry)
2) attachment to specific host tissue
3) resist host defense mechanisms (non-specific: TLR, cytokine, macs; specific: T & B)
4) damage host: invasiveness, toxigenicity

Front 7

Invasive Pathogenicity

Back 7

-damage is due to the growth of the bacterium in the host
-ex. encapsulated bacteria protected from phagocytosis

Front 8

Toxic Pathogenicity

Back 8

-limited or non-invasive growth at specific site in host
-bacterial proteins cause damage at sites distant from the infection
-ex. corynebacterium diphtheriae: infects trachae, secreted toxin damages all major organs

Front 9

bacterial endotoxins

Back 9

-heat stable
-Gram - only
-fever response via IL-1
-require higher amounts for a response
-ex. LPS

Front 10

bacterial exotoxins

Back 10

-heat labile (proteins)
-Gram + and -
-no fever response
-microgram amounts for response
-entire pathology often d/t toxin
-immunogenic: toxoid forms in vaccines (active immunity) or anti-toxin abs (passive immunity)

Front 11

Classes of bacterial toxins (4)

Back 11

1) surface acting toxins
2) pore forming toxins
3) A/B toxins
4) Type III and IV secretion

Front 12

Intracellular targets of A/B toxins

Back 12

-covalent modification to host macromolecules (ADP-ribosylation, proteolysis, glucosylation, deamidation, deadenylation)

Front 13

Protoxins

Back 13

-secreted form
-stable in the environment, but inactive
-activated by proteolysis, DTT, urea, nucleotides

Front 14

ADP-ribosylating exotoxins

Back 14

NAD + host protein -> ADP-ribose-host protein + nicotinamide

Front 15

Diphtheria: vaccination

Back 15

-microgram amounts are lethal to a non-immunized person
-vaccine = formalin inactivated diphtheria toxin (diphtheria toxoid)
-carrier for conjugate vaccines, Hib (immunogenicity)

Front 16

Nonlysogenic vs lysogenic diphtheria strains

Back 16

-diphtheria toxin encoded w/in beta phage
-nonlysogenic: URT, local infection, no systemic pathology, non-invasive
-lysogenic: URT, local infection, systemic pathology d/t diphtheria toxin -> heart, liver, lung, nervous system

Front 17

Diphtheria Toxin

Back 17

Two Subunits
1) A: 1 domain, catalytic
2) B: 2 domains (R - receptor binding; T - translocation)

Front 18

Diphtheria Toxin: Mechanism

Back 18

-receptor mediated endocytosis (R)
-upon acidification of endosome, T domain inserts into membrane
-translocates A subunit into cytoplasm
-A subunit ADP-ribosylates E2F -> inactive, inhibits protein synthesis

Front 19

Treatment of Diphtheria

Back 19

-administer antitoxin: Ab directed against receptor binding domain of toxin
-produced in horses, check for hypersensitivity (anaphylaxis risk)