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Questions and Answers
What does pathogenicity refer to?
What does pathogenicity refer to?
What is virulence specifically related to?
What is virulence specifically related to?
Which of the following is NOT a step necessary for an organism to cause disease?
Which of the following is NOT a step necessary for an organism to cause disease?
Which of the following is a factor that promotes bacterial colonization in the host?
Which of the following is a factor that promotes bacterial colonization in the host?
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What role do virulence factors that damage the host play?
What role do virulence factors that damage the host play?
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What is one way bacteria can resist innate immune defenses?
What is one way bacteria can resist innate immune defenses?
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How do motile bacteria improve their chances of colonization?
How do motile bacteria improve their chances of colonization?
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What factor influences whether a person contracts an infectious disease?
What factor influences whether a person contracts an infectious disease?
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What allows spirochetes to penetrate host mucous membranes more effectively?
What allows spirochetes to penetrate host mucous membranes more effectively?
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What mechanism does Helicobacter pylori use to protect itself from stomach acid?
What mechanism does Helicobacter pylori use to protect itself from stomach acid?
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What is one outcome of the inflammatory response triggered by Helicobacter pylori?
What is one outcome of the inflammatory response triggered by Helicobacter pylori?
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What function does streptokinase serve in the infection process of Streptococcus pyogenes?
What function does streptokinase serve in the infection process of Streptococcus pyogenes?
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How do bacteria resist being physically removed from the body?
How do bacteria resist being physically removed from the body?
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What type of immune response is triggered by Helicobacter pylori in the stomach?
What type of immune response is triggered by Helicobacter pylori in the stomach?
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What is the result of the damage to the gastric mucosa caused by Helicobacter pylori?
What is the result of the damage to the gastric mucosa caused by Helicobacter pylori?
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What role does DNase play in the pathogenicity of Streptococcus pyogenes?
What role does DNase play in the pathogenicity of Streptococcus pyogenes?
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What process allows bacteria to activate genes involved in virulence upon attachment to host cells?
What process allows bacteria to activate genes involved in virulence upon attachment to host cells?
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What enables certain bacteria to evade antibodies by genetically altering their pili?
What enables certain bacteria to evade antibodies by genetically altering their pili?
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Which of the following are proteins that enable bacteria to adhere to host cells?
Which of the following are proteins that enable bacteria to adhere to host cells?
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What structure do many bacteria form on host tissue to enhance adherence and protection?
What structure do many bacteria form on host tissue to enhance adherence and protection?
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Which invasin enables Streptococcus pneumoniae to enter host cells and resist phagocytosis?
Which invasin enables Streptococcus pneumoniae to enter host cells and resist phagocytosis?
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What is a common role of invasins produced by bacteria?
What is a common role of invasins produced by bacteria?
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The ability to compete for nutrients directly relates to what aspect of pathogenic bacteria?
The ability to compete for nutrients directly relates to what aspect of pathogenic bacteria?
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Which of the following is NOT associated with bacterial virulence?
Which of the following is NOT associated with bacterial virulence?
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What is one reason bacterial generation time is slower in the body than in lab culture?
What is one reason bacterial generation time is slower in the body than in lab culture?
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What are pathogen-associated molecular patterns recognized by during unenhanced attachment?
What are pathogen-associated molecular patterns recognized by during unenhanced attachment?
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What do pathogens need to do to establish infections effectively?
What do pathogens need to do to establish infections effectively?
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What is the process called when IgG or complement proteins enhance the attachment of microbes to phagocytes?
What is the process called when IgG or complement proteins enhance the attachment of microbes to phagocytes?
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What are siderophores?
What are siderophores?
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How do bacteria compete for iron in the body?
How do bacteria compete for iron in the body?
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Which of the following is a component of the complement pathways?
Which of the following is a component of the complement pathways?
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What is the function of lysosomes in phagocytosis?
What is the function of lysosomes in phagocytosis?
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What does the body produce to limit free iron availability?
What does the body produce to limit free iron availability?
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How many complement pathways are there in total?
How many complement pathways are there in total?
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What happens when iron concentrations are low in the body?
What happens when iron concentrations are low in the body?
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What must occur before a phagocyte can engulf a microbe?
What must occur before a phagocyte can engulf a microbe?
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Which function is NOT performed by activated complement proteins?
Which function is NOT performed by activated complement proteins?
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What do many pathogenic bacteria do to utilize the iron from other bacteria?
What do many pathogenic bacteria do to utilize the iron from other bacteria?
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What role do capsules play for certain bacteria in relation to phagocytosis?
What role do capsules play for certain bacteria in relation to phagocytosis?
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What is the first step in the process of phagocytosis?
What is the first step in the process of phagocytosis?
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What role do capsules play in bacterial resistance to phagocytosis?
What role do capsules play in bacterial resistance to phagocytosis?
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How does coagulase contribute to bacterial evasion of the immune system?
How does coagulase contribute to bacterial evasion of the immune system?
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What does the Type III secretion system do for bacteria?
What does the Type III secretion system do for bacteria?
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Which of the following is a method bacteria use to evade antibody responses?
Which of the following is a method bacteria use to evade antibody responses?
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What is one way bacteria prevent the fusion of phagosomes with lysosomes?
What is one way bacteria prevent the fusion of phagosomes with lysosomes?
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How do some bacteria avoid detection by antibodies due to their capsule?
How do some bacteria avoid detection by antibodies due to their capsule?
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What is a method bacteria use to resist phagocytic destruction?
What is a method bacteria use to resist phagocytic destruction?
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Why might bacteria vary their surface proteins?
Why might bacteria vary their surface proteins?
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Study Notes
Pathogenicity & Virulence
- Pathogenicity and virulence describe an organism's ability to cause disease.
- Pathogenicity refers to differences between microbial species.
- Virulence refers to differences between strains of the same species.
- In practice, they are often used interchangeably.
To Cause Disease
- An organism must:
- Maintain a reservoir (e.g., humans, animals, environment) before and after infection.
- Leave the reservoir and access a new host.
- Colonize the new host's body.
- Harm the body.
Influences
- Factors that influence the organism's ability to cause disease include its structures and metabolic products.
- Whether or not a person contracts a disease depends not only on the microorganism but also on the number of bacteria that enter the body and the quality of the individual's immune defenses.
Virulence Factors
- Bacterial virulence factors are divided into two categories:
- Factors that promote bacterial colonization of the host.
- Factors that damage the host.
Virulence Factors Promoting Colonization
- These factors enable bacteria to:
- Contact host cells.
- Adhere to host cells and resist physical removal.
- Invade host cells.
- Compete for iron and other nutrients.
- Resist innate immune defenses (e.g., phagocytosis).
- Evade adaptive immune defenses.
Ability to Contact Host Cells
- Motile bacteria that can swim chemotactically toward mucosal surfaces have a better chance to contact mucous membranes, attach, and colonize; mucosal surfaces (e.g., bladder, intestines) constantly flush bacteria away to prevent colonization.
- Spirochetes, due to their thinness, internal flagella, and motility, are more readily able to penetrate host mucous membranes, skin abrasions, etc., enter the body and disseminate to other body sites.
Ulcers: H. pylori
- Helicobacter pylori swims through the stomach's mucus layer and adheres to the epithelial cells.
- To protect itself from stomach acid, it produces an acid-inhibitory protein.
- The bacterium then releases toxins damaging the gastric mucosa.
- This leads to a massive inflammatory response with leukocytes killing bacteria, but also damaging the mucus membranes.
- Without the mucus layer, gastric acid causes stomach ulcers.
Streptococcus pyogenes
- Streptococcus pyogenes produces streptokinase to lyse fibrin clots, allowing the infection to spread.
- The bacterium also produces DNase that degrades cell-free DNA in pus and reduces its viscosity.
- Both enzymes facilitate spread to new tissues.
Ability to Adhere to Host Cells and Resist Physical Removal
- The body's innate defenses physically remove bacteria through shedding of surface epithelial cells, coughing, sneezing, vomiting, diarrhea, and bodily fluids (e.g., saliva, blood, mucus, urine).
- Bacteria may resist physical removal by producing pili, cell wall adhesins, and/or biofilm-producing capsules.
Signal Transduction
- Physical attachment of bacteria to host cells can signal the activation of virulence-related genes.
- This is known as signal transduction.
Pili and Bacterial Adherence
- Some bacteria alter the adhesive tips of their pili to adhere to and colonize different cell types with diverse receptors and evade antibodies.
Adhesins
- Adhesins are proteins in the cell walls of various bacteria.
- They bind to specific receptor molecules on host cells, enabling intimate attachment, colonization, and resistance to physical removal.
- Many bacteria utilize one or more adhesins for colonization.
- Bordetella pertussis produces multiple adhesins.
Capsules and Biofilms
- Many normal flora bacteria produce a capsular polysaccharide matrix or glycocalyx.
- This forms a biofilm on host tissues.
- Biofilms are layers of bacterial populations adhering to host cells.
- Embedded in a common capsular mass, they are found in situations like dental plaque and inner ear infections.
Ability to Invade Host Cells
- Some bacteria produce adhesin molecules called invasins.
- These activate the host cell's cytoskeletal machinery, enabling bacterial entry by phagocytosis.
- Bacteria entering the cytoplasm are protected from complement, antibodies, and other body defenses.
Examples
- Streptococcus pneumoniae produces phosphorylcholine, an invasin enabling entry to cells and resisting phagocytosis.
- Streptococcus pyogenes's F and M proteins aid invasion of epithelial cells and maintain persistent infections.
Ability to Compete for Iron and Other Nutrients
- Pathogenicity is related to the bacterium's ability to successfully compete with host tissue and normal flora for limited nutrients.
- The generation time of bacteria in the body is typically slower than in a lab culture due to limited nutrients.
Nutritional Competition
- To be pathogenic, a bacterium must multiply in host tissue.
- The rate of bacterial replication is correlated with the probability of infection establishment.
- Bacteria compete for nutrients: synthesis of specific transport systems or cell wall components aiding nutrient uptake.
- Bacteria compete for iron, where the host body also makes adjustments to deprive the microorganism of this essential nutrient.
Siderophores
- Bacteria synthesize iron chelators called siderophores.
- Many siderophores are excreted and re-enter the cell to bind iron.
- Others are found on the cell wall, binding and transporting the iron into the bacterium.
- The concentration of free iron is low due to host-produced iron chelators.
Other Ways of Acquiring Iron
- Some bacteria produce receptors for siderophores from other bacteria, taking iron from them.
- Some pathogenic bacteria bind human iron-binding proteins like transferrin, lactoferrin, ferritin, and hemin as the iron source.
- Bacteria can secrete exotoxins to kill host cells, accessing iron if concentrations are low.
Resist Innate Immune Defenses
- Overview of Phagocytosis: The microbe surface must attach to the phagocyte's cytoplasmic membrane for ingestion.
- Unenhanced attachment generally recognizes pathogen-associated molecular patterns in microbial cell walls, not found on human cells.
- These patterns are recognized via endocytic pattern-recognition receptors on phagocytes.
Enhanced Attachment
- Enhanced attachment occurs through antibody molecules (e.g., IgG) or complement proteins (e.g., C3b, C4b) called opsonins that promote attachment.
- This process, known as opsonization, is more specific and efficient than unenhanced attachment.
Phagocytosis Continued
- Following attachment, polymerization and depolymerization of actin filaments forms pseudopods to engulf the microbe into a phagosome.
- Lysosomes fuse with the phagosome, digesting and destroying the microbe.
Complement Pathways
- Bacteria can interfere with the body's complement pathways.
- There are three pathways: classical, alternative, and lectin.
- These pathways, though activated differently, all produce beneficial complement proteins.
Complement Proteins
- Complement proteins are a set of serum proteins.
- When activated, they participate in: inflammation, phagocyte chemotaxis, opsonization, and lysis of membranes.
Capsules
- Capsules enable organisms to resist phagocytic engulfment.
- Capsules of some bacteria interfere with the body's complement pathways.
Other ways to resist phagocytosis
- Coagulase induces fibrin clot formation, which helps to resist phagocytosis.
- Pathogenic Yersinia, using a type III secretion system, delivers proteins that depolymerize actin microfilaments, needed for phagocytic engulfment.
The Type III Secretion System
- The bacterium produces pore-forming proteins that create a pore spanning the bacterium's and outer membrane and the host cell's plasma membrane.
- The system allows the bacterium to directly deliver proteins into the host cell cytoplasm.
Bacteria Resisting Phagocytic Destruction
- Escape from the phagosome into the cytoplasm prior to phagosome/lysosome fusion.
- Preventing phagosome/lysosome fusion by inserting por proteins.
- Producing enzymes that kill the phagosome.
Evading Adaptive Immune Defenses
- A major defense against bacteria is antibody production, with antibody tips (Fab regions) having shapes complementary to the bacterial proteins and polysaccharides (epitopes).
Avoiding Antibodies
- Bacteria alter adhesive tips of pili or surface proteins to avoid antibodies.
- Antibodies may not be made against some capsules.
- Bacteria coat themselves with host proteins like fibronectin, lactoferrin, or transferrin to avoid antibody binding.
Virulence Factors Damaging the Host
- The ability to produce cell wall components (PAMPs) that cause host cells to produce inflammatory cytokines.
- The production of harmful exotoxins.
- The ability to induce autoimmune responses.
Autoimmunity and Exotoxins
- Autoimmunity occurs when the body's immune defenses mistakenly attack the body (trigger often bacteria).
- Exotoxins are protein toxins secreted by living bacteria or released upon lysis.
- Three types:
- Superantigens (Type I toxins).
- A-B toxins and other toxins interfering with host cell function (Type III toxins).
- Exotoxins damaging host cell membranes (Type II toxins).
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