Bacterial Toxins Flashcards
Saprophytes
- Organism that is not associated with disease
- Free living bacteria
- Most bacteria - Bacillus spp.
Commensals
- Organims that live in association with a host
- Relationship benefits both organisms
- Most bacteria that live within a host - Staphylococcus
Opportunistic pathogens
- Organism that causes disease in a compromised host: immune, physical, or chemical - Pseudomonas Staphylococcus
Pathogen
Organism that is capable of causing disease in a “normal host” - Bacillus antracis, Corynebacterium diptheriae
Virulence
Degree of pathogenicity
4 final outcomes of bacterial infection
- Death
- Recurrent illnesses
- Recovery and cure
- Asymptomatic Infection
* As number of bacteria increase, likelihood of death increases
Properties of a successful pathogen (4)
- Gain access into the host
- Colonize host tissue
- Resist host defense mechanism
- Damage host
Two mechanisms of pathogenesis
- Invasiveness
- Toxigenicity
Pathology due to the invasive properties of a bacterium
Microbe enters, colonizes, and grows in the host; damage is due to the growth of bacterium in the host
Pathology due to toxins produced by the bacterium
- Microbe enters, colonizes, and grows in the host, typically at a specific site in the host (non-invasive)
- Bacteria produce proteins that damage at sites distanced to site of infection
Toxoid
A substance that has been treated to destroy its toxic properties but retains the capacity to stimulate production of antibodies, used in immunization
General properties of bacterial exotoxins (7)
- Produced by both gram positive and gram negative bacteria
- Heat labile
- Immunogenic → anti-toxin antibodies can neutralize toxin
- Immunogenic → converted to a toxoid by chemical treatment to generate a vaccine
- Mode of action does not include fever in host
- Toxic at microgram amounts
- Often responsible for entire pathology of pathogen
Four classes of bacterial toxins
- Surface-acting toxins - bind to receptor
- Pore-forming toxins - form channel to release nutrients from host cell
- A/B toxins - A component is enzymatic; B component is for binding
- Type III and IV secretion - paralyze host cell to prevent phaogocytosis of the pathogen
Toxins are ______ that are enzymes that modify specific host __________
Proteins; macromolecules
Modifications from Diptheria toxin and Pseudomonas aeruginosa exotoxin A:
ADP-ribosylate EF2: inhibits protein synthesis
Modifications from Botulinum toxin and Tetanous toxin:
Protease for SNARE proteins
Modifications from Large clostridium difficile toxins:
Glucosylate Rho proteins
Modifications from Shiga toxin:
Deadenylate adenine on RNA
Protoxins
- Bacteria secrete toxins in a protoxin form that is stable to the environment, but not active until protein has been modified
- Activation by proteolysis, disulfide bond reduction
Today’s application of Diptheria:
Vaccine - formalin inactivated diptheria toxin
Carrier - for conjugate vaccines (Hib) - CRM 197 a point mutation within DT that inactivates toxin
Entry of diptheria toxin into eukaryotic cells
- Diptheria toxin inhibits protein synthesis: ADP-r-EF2
- Pathology within the heart, liver, lung, and nervous system
- Death due to cardiac failure
Diptheria, Tetanus, and Pertussis vaccines (4 combination vaccines)
Four combination vaccines: DTaP, Tdap, DT, and Td
DTaP and DT are given to children < 7yrs
Tdap and Td are given to older children and adults
Children should get __ doses of DTaP at __, __, __, and __ - ___ months of age and __ - ___ years
5; 2; 4; 6; 15-18; 4-6
___ does not contain pertussis, and is used as a substitute for DTap for children who cannot tolerate pertussis vaccine
Td
WHen should women recieve additional Tdap
During each of their pregnancies
Adolescents 11-18 years of age and adults 19 and older should recieve a single dose of ____
Tdap
Major catalysts for Russian diptheria outbreak in 1990s
- Increased proportion of susceptible individuals in the population due to migration of the population
- A deteriorated health infrastructure (vaccination programs)
what does the “a” in DTaP and Tdap stand for?
acellular - pertussis component contains only a part of the pertussis organism