Bacterial pathogenesis Flashcards
What is immune selection and what is an example?
Bacteria know our immune system better than we do so they use it for their benefit
Relapsing fever is driving force for antigenic variation in Borrelia hermsii
Pathogenic bacteria are often clonal. How do they differ from nonpathogenic bacteria?
They have additional virulence genes
Is antibiotic resistance more commonly selected in a population or individual?
Population
What are Koch’s postulates for?
Guidelines for establishing the cause of an infectious disease
What are Koch’s postulates?
- Microorganism found in all cases of disease and in right spot
- Microorganism can be grown outside the host for several generations
- Reinoculation of the cultivated microorganism causes the disease
- Microorganism can be isolated from experimentally produced disease
What are two examples of organisms that can’t be cultured?
Treponema pallidum (syphilis) - use rabbit testes Tropheryma whipplei (Wipple's disease) - use PCR
Name an organism that does not have an animal model?
Neisseria gonorrheae
Transmissibility: is it better to have a clinically mild or strong disease?
Clinically mild because a well adapted bug doesn’t want to kill its host
Why are there clinically symptomatic diseases?
Non-adapted host or pathogen (zoonotic bacteria)
Clinical symptoms that promote transmission
Disease manifestations that are due to host response to pathogen
5 ways that bacteria can spread in the body?
Direct tissue spread vascular lymphatic within macrophages ascending/descending within body tracts
Extracellular bacteria often cause disease via the effect of?
Toxins and enzymes
Intracellular bacteria are able to do what?
Invade host cells and often cause chronic infections
What are exotoxins?
Highly toxic proteins secreted by bacteria into the extracellular environment
Often have two subunits (A and B)
What do the A and B subunits of exotoxins do?
A: active subunit with specific toxin activity
B: binds to specific host cell receptor; involved in entry of exotoxin into cell
Corynebacterium diptheriae is an example of what? What is the mechanism?
AB subunit exotoxin
Inhibition of protein synthesis, cell death
What is food poisoning commonly caused by?
staphylococcal enterotoxin or botulinum toxin
What is usually required for toxin production to occur?
Active bacterial infection
How does enterotoxin vibrio cholerae cause diarrhea?
It is an AB exotoxin that induces adenylate cyclase activity which increases cAMP which causes increased secretion of cell nutrients, causing diarrhea
How does neurotoxin clostridium tetani work?
It is a AB subunit exotoxin that blocks inhibitory nt release which causes continuous stimulation by the excitatory nt … causing spastic paralysis
How does the neurotoxin clostridium botulinum work?
AB exotoxin that blocks the release of ACH from vesicles which causes flaccid paralysis of muscles
How does bacillus anthracis work?
3 proteins make up 2 toxins
“protective antigen” is the B subunit
The A subunits are: edema factor (an adenylate cyclase) and lethal factor (kills cells)
superantigens vs exotoxins and fever?
Superantigens cause fever while exotoxins do not
Although some exotoxins are superantigens
What are superantigens produced by?
bacteria and viruses
How do superantigens work? Two examples?
Polyclonal stimulation of T cells to divide and produce cytokines
Staph Toxic Shock Syndrome Toxin-1
Strep exotoxins
What are pyrogenic toxins?
Cause fever unlike other exotoxins
Exotoxins are partially denatured by treatment with what? What does it create?
Formalin, acid, or heat
Creates a toxoid (nontoxic but still antigenic)
What are toxoids used for? 2 examples
Immunization
Diphtheria and tetanus toxoids
Exotoxins are highly _________ and _______ labile
highly antigenic
heat labile
Endotoxin is also known as what? It is an integral part of what?
LPS - lipopolysaccharide
Gram - bacteria cell wall
Describe the LPS cascade that causes septic shock
Endotoxin in the bloodstream binds to receptors on macrophages which signals a cytokine release which activates inflammatory and coagulation cascades
Septic shock can also be caused by gram + bacteria, even though they don’t have LPS… why?
Probably due to peptidoglycan even though it is less potent
What part of LPS is the toxic moiety?
Lipid A
Which is more toxic, LPS or exotoxin?
Exotoxin
Exotoxin: gram - or + ?
Both
Endotoxin: gram - or +?
gram -
Exotoxin vs endotoxin, how are they released?
Exotoxin is secreted
Endotoxin is released once cell is lysed
Which is more toxic, endotoxin or exotoxin?
Exotoxin
Which is more antigenic, endotoxin or exotoxin?
Exotoxin
Reaction to heat: endotoxin vs exotoxin
Endotoxin is heat table
Exotoxin is inactivated to form toxoid
Which causes fever, endotoxin or exotoxin?
Endotoxin causes fever and septic shock
However pyrogenic toxins cause fever, and some exotoxins are pyrogenic
Are all bacterial enzymes intrinsically toxic?
No
How to bacterial enzymes cause tissue damage? What are they destroying?
Connective tissue
Also degrades hyaluronic acid (hyaluronidase)
What is streptokinase?
Fibrinolysin - blood clots
What is coagulase?
Coagulates plasma
What is catalase?
Inhibits oxidative killing
Gram - don’t have
What do cytolysins do?
Kill host cells
What is Streptolysin S?
Group A beta-hemolytic streptococci
What is the first step in entry to the host cell and secretion of bacterial proteins into the host cell?
Adherence to host cell
Antibodies against what can block adhesion of bacteria to host cells?
Antibodies against adhesin
What can cause pyelonephritis?
P pilus of E. coli
What is the type III secretion system? Which bacteria type have it?
Used for secreting bacterial virulence proteins into host cells
Only in pathogenic gram -
For the secretion of bacterial proteins into host cells, what are their two different functions?
induce/prevent uptake by mammalian cell
induce/prevent death of mammalian cell
What is an example of a bacteria that induces uptake by a mammalian cell? One that prevents uptake?
Salmonella - invades mammalian cells
Yersinia - prevents phagocytosis by macrophages
What is an example of a bacteria that induces cell death? One that prevents it?
Yersinia induces apoptosis of macrophages
Chlamydia prevents apoptosis (intracellular bacteria)
What are three advantages of intracellular localization?
Nutrient rich environment
Absence of competing microorganisms
Protected from humoral immune system
Intracellular bacteria that survives inside a phagolysosome?
Coxiella
Intracellular bacteria that inhibits phagolysosomal fusion?
Chlamydia
Intracellular bacteria that escapes into cytosol?
Listeria
Diagram the intracellular life cycle of listeria
Entry by internalin Lysis of vacuole by listeriolysin O Escape into cytosol Actin based motility by ActA Spread to adjacent cell Lysis of vacuole... etc
What bacteria absorbs normal host component to surface of itself to avoid host immune system?
Staphylococcus aureus (protein A binds IgG)
What are 3 surface factors that inhibit phagocytosis?
Polysaccharide capsule
M protein: group A streptococci
Pili : neisseria gonorrheae
Why does the polysaccharide capsule aid in evasion of host immune system?
Prevents complement deposition and is poorly immunogenic
Induces T cell independent immune response
Response is poor in children <2
What are 3 bacteria that utilize the polysaccharide capsule to evade immune systems?
Bacteria that cause meningitis
neisseria meningetidis
streptococcus pneumoniae
haemophilus influenzae
Are antibodies against polysaccharide capsular type general or specific? What do these antibodies protect against?
Have to be specific
Protect against serious systemic infection
Do not protect against mucosal colonization
Example of 2 bacteria that switch surface antigens?
neisseria gonorrheae: (lipooligosaccharide, pili, Opa proteins)
borrelia hermsii - relapsing fever
What is an IgA protease, which 4 bacteria produce it?
Cleaves IgA, which is important for mucosal immunity
neisseria gonorrheae, neisseria meningitidis, haemophilus influenzae, streptococcus pneumoniae
Deposition of immune complexes cause tissue damage. What is an immune complex?
bacterial antigen, antibody, complement
What happens in post-streptococcal acute glomerulonephritis
Deposition of immune complexes in glomeruli of kidneys
What happens in post-streptococcal rheumatic fever?
Autoimmune process with antibodies against streptococcal antigen cross-reacting against host tissue
Where is extracellular iron bound in plasma and milk/other secretions?
Transferrin
Lactoferrin
What is an example of a bacteria that produces siderophores to capture iron?
E. coli
Bordetella pertussis has higher expression of virulence genes at what temperature?
Higher expression at 37 degrees than 20 degrees
Yersinia antiphagocytic factors have higher expression in the absence of what
Ca2+
Corynebacterium diptheriae toxin is more highly expressed in the presence of low what
Fe3+
What are three main mechanisms of antibiotic resistance?
Inhibition of antibiotic
Target site alteration
Decreased intrabacterial accumulation of antibiotic
Inhibition of antibiotic occurs by:
Example
enzymatic hydrolysis of antibiotic
Ex. enteric gram - bacteria that produce beta lactamases
Target site alteration occurs by:
3 examples
Decreasing binding affinity for the antibiotic for the target
penicillin resistant streptococcus pneumoniae expressing altered penicillin binding protein (PBP)
methicillin resistant staphylococcus aureus expressing altered PBP
vancomycin resistant enterococcus expressing altered cell wall oligopeptide
3 ways in which there could be decreased intrabacterial accumulation of the drug, and one example
Decreased membrane permeability
Changes in porin channels
Increased drug efflux often resulting in multidrug resistance
Psuedomonas aeruginosa uses all 3 mechanisms
Can plasmids be passed by conjugation
Yep
One example of virulence genes encoded by a prophage?
vibrio cholerae
Streptococcus pyogenes containing erythrogenic toxin cause
scarlet fever
E. coli strains that produce shiga toxin cause what
hemorrhagic colitis and hemolytic uremic syndrome
What are examples of virulence factors? 5
Toxins Enzymes Type III secreted proteins Adhesins Siderophores
toxins were originally inactivated into toxoids by _________ and _______ but now can be genetically engineered
Heat, formaldehyde
What is antitoxin?
Antisera produced in response to the toxoid (from humans/animals) and can be given as treatment
