Bacterial Pathogens and Disease I-Exotoxins Flashcards
What is the difference between :
- Pathogen
- Pathogenicity
- Virulence
- Toxigenicity
Pathogen = A microorganism capable of causing disease
Pathogenicity = The ability of an infectious agent to cause disease
Virulence = The quantitative ability of an agent to cause disease
Toxigenicity = The ability of a microorganism to produce a toxin that contributes to the development of disease
- What are some factors/mechanisms that affect the virulence of an agent?
Adherence Factors, Biofilms,
Invasion of host cells and tissues,
Toxins (endotoxins and exotoxins).
- What are exotoxins?
- Heterogeneous group of proteins produced and secreted by living bacterial cells
- Cause disease symptoms in host during disease.
- Act via a variety of diverse mechanisms.
- What type of bacteria produce exotoxins
- gram negative, gram positive or both?
Both gram + and gram -
- Exotoxins give bacteria a selective advantage?
o They Cause disease – may help transmission of disease, however in severe disease host may be a literal and evolutionary dead end.
o However, with many toxins the disease causing activity may be not be the primary function.
- What do exotoxins do and how does this result in an evolutionary adavantage?
o Evade immune response o Enable biofilm formation o Enable attachment to host cells. o Escape from phagosomes • All allowing for colonisation, niche establishment and carriage - Evolutionary advantage.
- What happens when a person gets infected with Staphylococcus aureus?
- Entry
- Produce haemolytic toxins:
- α,β,δ, toxins ,Panton Valentine Leukocidin (PVL), LukAB, LukED, LukMF
- Phenol soluble modulins PSM (S.aureus codes for 8) (toxins, biofilm production) - Cause cells to lyse by forming pores
- Aggregate the lipid bilayer of host cells - lysis
- Majority of S. aureus in humans is asymptomatic carriage in the nose.
• So what are those toxins doing in the nose?
•These bacteria are spread by having direct contact with an infected person, by using a contaminated object, or by inhaling infected droplets dispersed by sneezing or coughing.
- What genes encode exotoxins?
Can be encoded by chromosomal genes Shiga toxin in Shigella dysenteriae, TcdA & TcdB in C. difficile
- Many toxins are encoded by extrachromosomal genes
Give examples of the toxins coded in plasmids and Lysogenic Bacteriophage?
o Plasmids – Bacillus anthracis toxin, tetanus toxin
o Lysogenic bacteriophage – e.g. streptococcal pyrogenic exotoxins in Scarlet Fever, Diphtheria toxin.
- One way of classifying exotoxins is through their toxin activity, how would they be classified then?
- Membrane Acting Toxins – Type I
- Membrane Damaging Toxins – Type II
- Intracellular Toxins – Type III
- What is the problem with classifying exotoxins based off toxin activity
o Many toxins may have more than one type activity.
o As mechanisms better understood (how the toxin works) this classification tends to break down.
- How do the “ Membrane acting Type 1 Toxins “
- Act
- interfere
- whats their target
• Act from without the cell.
• Interfere with host cell signaling by inappropriate activation of host cell receptors.
•Target receptors including: –Guanylyl cyclase → ↑ intracellular cGMP
-Adenyl cyclase → ↑
intracellular cAMP
-Rho proteins
-Ras proteins
- One example of the Membrane acting Type 1 Toxins is E.Coli Stable heat toxins - how does this toxin specifically work?
Sta binds to the GCR to increase the formation of cGMP.
• This activates many intracellular signal transduction pathways e.g. cGMP.
• This changes the permeability of ion pores e.g. increased Cl- excretion (water follows it and causes diarrhoea).
- How do the Membrane Damaging Type 2 Toxins work?
Cause damage to the host cell membrane:
•Insert channels into the host cell membrane.
eg : β sheet toxins e.g. S.aureus α – toxin, δ toxin, PVL
oα helix toxins – e.g. diphtheria toxin
•Enzymatical damage e.g. S. aureus β- haemolysin, PSM
- What are the two types of Membrane Damaging Type 2 Toxins?
Receptor mediated: use toxin-specific receptor to form defined ion pores = alpha toxin, Luk-(AB,GH,DE), PVL
Receptor Independent: attach to membrane and disintegrate it to form short-lived pores.(mainly alpha type PSMs)
- How do the “Intracellular Type 3 Toxins” work?
• Active within the cell – must gain access to the cell
• Usually 2 components – AB Toxins
o Receptor binding and translocation function – B
oToxigenic (enzymatic) – A
o May be single or multiple B units e.g. Cholera toxin AB5
- The enzymatic component A of intracellular type 3 toxins has a wide array of activities- list some
o ADP – ribosyl transferases - e.g. Exotoxin A of Pseudomonas aeruginosa, pertussis toxin.
o Glucosyltransferases – e.g. TcdA and TcdB of Clostridium difficile
o Deamidase – e.g. dermonecrotic toxin of Bordetella pertussis.
o Protease – e.g. Clostridial neurotoxins: botulism & tetanus
o Adenylcyclase - e.g. EF toxin of Bacillus anthracis.
- How does YopE inject its toxin into the host cell
o Type III secretion and toxin injection e.g. YopE in Yersinia species – membrane produces a needle structure to inject the toxin in.
- What are some cytokines that exotoxins are able to release via an inflammatory cytokine release?
IL1, IL1β, TNF, IL 6,δ interferon, IL18.
