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Questions and Answers
What does LD50 represent in the context of animal infection studies?
Which of the following is NOT a step required for a microorganism to cause disease?
In competition assays for determining LD50 and ID50, what do mutant and wild-type bacteria compete for?
Which portal of entry is associated with respiratory diseases?
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What is the role of pili in bacterial infections?
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What is one effect that non-piliated E. coli has on urinary tract infections (UTIs)?
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What is meant by the 'stringent response' in bacteria?
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Which of the following factors is NOT involved in the adhesion and colonization of bacteria?
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What is the main goal of understanding bacterial pathogenesis?
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Which of the following is NOT one of the Molecular Koch's Postulates?
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What does virulence refer to in the context of bacterial pathogens?
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Which of the following is an example of a legitimate intervention to prevent disease according to the fifth molecular Koch's postulate?
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Which statement accurately describes virulence factors?
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What is a significant consideration when choosing animal models for virulence measurement?
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The use of knockout or knock-in mice in injury models primarily addresses what aspect?
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Why are rodent models commonly utilized in infection research?
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What role do adhesins play in bacterial colonization?
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Which of the following host factors is NOT involved in bacterial colonization?
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What mechanism is employed by bacteria to resist host defenses through antigenic variation?
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How does a bacterial capsule inhibit host immune response?
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Which bacterial protein prevents opsonization by binding to the Fc region of antibodies?
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What is the function of super-antigens in bacterial resistance to host defenses?
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What mechanism does L.monocytogenes use to escape phagocytosis?
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Which example illustrates molecular mimicry in bacterial resistance?
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How do Salmonella serovar Thyphimurium evade the host response?
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What host condition can increase susceptibility to opportunistic infections?
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Which of the following is NOT a mechanism for bacteria to resist host defenses?
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Which property allows pathogens like Salmonella to invade host tissues?
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What is one role of phospholipases PlcA and PlcB in L.monocytogenes?
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Which type of toxin binds to targets at the cell surface but is not translocated into the cell?
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What host factor is degraded by bacterial fibrinolysin to aid in infection?
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What strategy can bacteria employ when faced with adverse pH conditions in the host?
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What is the primary function of superantigens?
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Which type of toxin is characterized by having both an enzymatic domain and a binding component?
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What mechanism do type II toxins utilize to affect host cells?
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Which component is crucial for the activity of A-B toxins?
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What characteristic defines endotoxins?
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Which type of secretion system is detailed as being specific to Gram-negative bacteria?
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What is the main role of the general secretory system (sec)?
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What effect do phospholipases have on cell membranes?
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Study Notes
Bacterial Pathogenesis
- Bacterial Pathogenesis is the process of how bacteria cause disease.
Molecular Koch's Postulates
- The gene or its products should be found in only in strains that causes disease.
- Gene should be isolated by cloning.
- Disruption of gene should should reduce or attenuate its virulence.
- Gene is expressed by bacterium at some point during infection.
- The fifth Postulate: Elimination of a disease causing microbe or prevention should eliminate or prevent disease.
Virulence
- Virulence is a measure of the how pathogenic a bacterium is; pathogenicity refers to the capacity of a microbe to produce disease.
- Virulence factors (or determinants): Gene products that allow a microorganism to establish itself within or on a host and enhance the potential to cause disease.
Measuring Virulence: Animal Models
- Ethical concerns are relevant when choosing animal models to test bacterial virulence.
- Rodent models are widely used, but there are benefits and disadvantages to using each.
- Knockout and knock-in mice: Mice with specific genes deleted or introduced, respectively.
- LD50 refers to the 50% lethal dose, the dose where 50% of animals die.
- ID50 refers to the 50% infectious dose, the number of bacteria needed to infect 50% of animals.
A Simple Animal Model
- An animal model is used to determine bacterial virulence.
- In a simple model, bacteria are inoculated into an animal, then the infected animal is sacrificed and the number of bacteria are measured.
- Competition assays can make LD50 and ID50 experiments more sensitive by seeing how mutant strains of bacteria compare to wild-type bacteria.
To Cause Disease, Microorganism must:
- Find and enter the host
- Colonize the host
- Resist host defenses
- Cause damage to, or malfunction of host tissue
Portals of Entry
- Ingestion - Fecal-oral route, contaminated food and water.
- Respiratory tract - Aerosols, contaminated hands
- Wounds - Scratches, bites
- STD - Sexual activity
- Medical devices - Catheters, contact lenses
- Normal flora movement or altered growth
Adhesion and Colonization
- Bacteria require mechanisms to attach to host cells and colonize a specific location.
- Pili are hair-like structures that play a role in adhesion.
- Flagella are used for motility.
- Capsule prevents the host immune system from recognizing the bacteria.
Resisting Host Defenses
- Bacteria have a repertoire of strategies to counter host defense mechanisms.
- Loss of bacterial antigen
- Overproduction of bacterial antigen binds up host antibodies, such as in the case of superantigens
- Capsules bind to serum proteins and inhibit complement activation.
- Altered bacterial antigen (antigenic variation) allows some bacteria to evade the host immune system.
- Molecular mimicry is when bacterial antigens mimic host molecules, effectively camouflaging the bacterium.
Immunoglobulin Resistance Strategies
- Protein A of S. aureus and Protein G of S. pyogenes bind to the Fc region of antibodies (immunoglobulins), preventing opsonization.
- Ig protease degrades immunoglobulins.
- Bind host materials
Escape from Phagocytosis
- Listeria monocytogenes: Secreted listeriolysin O (LLO) creates pores in phagosomal membranes, allowing the bacteria to escape into the cytoplasm, then multiply.
Penetration Strategies
- Salmonella: Delivers effector proteins into host cells to protect vacuoles and evade host immune response.
Other Strategies
- Blood clots: Bacteria can degrade clots with fibrinolysin.
- Mucus: Bacteria can produce enzymes to degrade mucus.
- Normal flora competition - Bacteria compete with other organisms and disrupt signals.
- Host signals - Some bacteria can disrupt host signals.
- Siderophores - Bacteria can acquire iron using siderophores.
- Adverse pH, low nutrients: Some bacteria have evolved the ability to survive in these environments.
Toxins
- Type I toxins bind to the cell surface and are not translocated into the cell.
- Type II toxins act on the cell membranes, such as phospholipases and pore-forming cytotoxins
- Type III toxins are typically A-B toxins with two functional components: an enzymatic domain (A) which inactivates intracellular targets and a binding component (B) which recognizes a surface receptor.
Endotoxin
- Lipopolysaccharide (LPS) is a toxin found in the outer membrane of Gram-negative bacteria.
Superantigens
- Superantigens (SAg) are Type I toxins from bacteria like Staphylococcus aureus, that bind to and stimulate a large number of T cells, leading to overproduction of cytokines and immune dysregulation.
Membrane Disruption (Type II Toxins )
- Alpha toxin from Staphylococcus aureus forms pores in cell membranes.
- Phospholipase C and hemolysins can remove polar head groups from phospholipids, disrupting the membrane.
Type III (A-B toxins)
- A-B toxins are typically synthesized as single polypeptide chains.
- The 'A' and 'B' domains separate by proteolysis.
Toxin Export
- Toxins are often produced inside the bacterial cell but act on the outside.
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Secretion systems are used to export toxins out of the cell:
- General secretory system (sec)
- Types I to VII secretion systems
- Cytolysin mediated translocation (CMT)
- ExPortal
- T7SS
General Secretory System (Sec)
- Found in Gram-positive and Gram-negative bacteria.
- Proteins synthesized with signal sequences (leader peptides) are recognized by Sec proteins which help transport the protein across the membrane.
- Once exported, the signal sequence is cleaved off.
Secretion Systems
- Sec-dependent secretion systems: T2SS and T5SS
- Sec-independent secretion systems: T1SS, T3SS, T4SS, T6SS
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Description
Explore the fascinating world of bacterial pathogenesis in this quiz. Learn about Molecular Koch's Postulates and the various factors that determine the virulence of bacteria. Test your knowledge on how bacteria cause disease and the ethical considerations of using animal models in research.
