Bacteriology 4: Bacterial Pathogenesis (diagnosis Is Separated)

Question 1

Define virulence factor:

Answer 1

Bacterial constituents that promote infection

Question 2

Steps in pathogenesis

Answer 2

Encounter: endogenous or exogenous
Entry: access- (toxins).. penetration of epithelial barrier
Spread: adjacent tissues to distant tissues
Multiply: incubation period/ immune evasion
Damage: disease (clinical/subclinical). Immunopathology (how the immune system response contributes to the development of the disease)
Outcome: symbiosis w/ organism. Clearance of organism. Death

Question 3

What type of pathogens cause disease even in healthy hosts?

Answer 3

True/primary pathogens

Question 4

Opportunistic pathogens

Answer 4

Cause disease under immunocompromised or unusual conditions

Question 5

What is dependent on the severity of the disease?

Answer 5

The condition of an individual plays an important role in whether disease occurs (age, health, ability of the host to protect itself)

Virulence of the organism and susceptibility of the host is what the disease severity is dependent on

Question 6

What do Virulence and virulence factors do?
What are some examples of virulence and virulence factors?

Answer 6

Virulence factors help the microbe adapt and/or invade the host. Virulence factors are critical for the pathogen’s ability to survive and proliferate in the host, and they may be encoded on various genetic elements, such as the chromosome, plasmids, or phage genomes (viruses that infect bacteria).

-adhesion (Fimbriae, pillie, binding factors)
-invasion (flagella, various toxins, enzymes) Pathogens produce enzymes that break down host tissues and allow them to invade deeper into the body.
Example: Streptococcus pyogenes produces hyaluronidase, which breaks down hyaluronic acid in connective tissues, facilitating spread
-toxins (LPS) Toxins disrupt host cell functions or directly cause cell death, leading to tissue damage and disease symptoms.
Example: Clostridium botulinum produces botulinum toxin, which blocks nerve function, causing paralysis
-immune system evasion(capsule, enzymes, toxins) Streptococcus pneumoniae has a polysaccharide capsule that prevents phagocytosis by immune cells.
-nutrient acquisition (diverse enzymes, iron-binding proteins) Some pathogens produce enzymes that break down host molecules to acquire nutrients.
Example: Staphylococcus aureus produces hemolysins that lyse red blood cells to obtain iron.

Virulence= the degree or strength of pathogenicity
Virulence factor= bacterial molecules that promote infection

Question 7

Infectious dose (ID50) vs. Lethal Dose (LD50)
-what type of relationship do they have?
-an example of a bacteria that is more virulent vs. one that is less virulent?

Answer 7

These are metrics used to assess the virulence or potency of a pathogen
-ID50= number of organisms required to cause infection in 50% of infected organisms
-LD50= number of organisms required to kill 50% of infected organisms

ID50 & LD50 have an inverse relationship with virulence. Therefore a low ID50/LD50 will have a high virulence

More virulent bacteria
= Francisella Tularensis(Rabbit fever)
=has a very low infectious dose (ID50) therefore is highly virulent

Less virulent bacteria
= Lactobacilli, diphtheroids, cholera Vibrio cholera
=has a very high infectious dose (ID50) therefore is less virulent.

Question 8

Adherence factors
-involves?
-what are some receptors and adhesion factors?
-example of a bacteria?

Answer 8

attachment mechanism
-adherence involves host receptors and bacterial adhesions

-host receptors = glycoproteins and sugars
-adhesion = Fimbriae, pillie, Flagella, Biofilm, binding factors
Flagella = composed of flagellin (motility)
(H antigen)
Fimbriae = shorter than Flagella
Pili = tubular structure
Biofilm = community of microorganisms embedded in a self-produced ECM attached to a surface

-Vibrio cholerae attaching to the intestinal epithelia
-E.coli attaching to intestinal microvilli
-Neisseria gonorrhoeae uses pili to attach to mucosal surfaces.

Question 9

Arrangements of bacterial flagelars

Answer 9

-Atrichous
-Monoatrichous
-amphitrichous
-Cephalotrichous
-Peritrichous
-Lophotrichous

Question 10

extracellular enzymes is considered for what type of virulence factor?
-examples of some extracellular enzymes?
-what do these virulence factors do?
-example of a bacteria?

Answer 10

invasion (flagella, various toxins, enzymes)
Pathogens produce enzymes that break down host tissues and allow them to invade deeper into the body.

ECM enzymes
-Hyaluronidase
-Collagenase
-coagulase
-kinases
-catalase

Examples
Salmonella invading the microvilli of intestinal cells. After adhering to the microvilli with its fimbriae. It injects proteins into the cell disrupting the actin filaments and surrounding the bacteria to pull it inside. Once inside it becomes shielding w/n a vacuole and begins to grow. From here it can gain entrance to nearby tissues.
Streptococcus pyogenes produces hyaluronidase, which breaks down hyaluronic acid facilitating spread*

Question 11

examples of some extracellular enzymes and what do they do?

Answer 11

ECM enzymes
-Hyaluronidase- allows bacteria to penetrate b/w cells. This will hydrolyze hyaluronic acid (intracellular cement)
-Collagenase - degrading CT
-coagulase - formation of fibrin clot (from fibrinogen). This will coat and protect the bacteria (walling-off process)
-kinases- degrade fibrin (dissolving clot) Expression of this enzyme is controlled by quorum sensing.
-catalase - degraded H202 into H20 and O2

Streptococcus pyogenes produces hyaluronidase, which breaks down hyaluronic acid penetrating b/w cells, then using collagenase to degrade the CT facilitating spread

Bacteria producing coagulase, and forming a clot. Then the bacteria producing kinase to dissolve clot and release bacteria.

Question 12

Endotoxins are only found in what type of bacteria? Provide an example of a bacteria

Answer 12

Gram (-)
toxins composed of lipids that are part of the cell wall
Endotoxins: Lipid portions of LPS that are part of the outer membrane of the cell envelope of gram (-) bacteria (Lipid A). The endotoxins are liberated when the bacteria die and the cell wall lyses.

example
Salmonella Typhimurium

Question 13

Exotoxins are found primarily in what type of bacteria? Provide an example of a bacteria

Answer 13

toxic substances released outside the cell
-proteins produced inside pathogenic bacteria, most commonly gram (+) bacteria, as part of their growth and metabolism. The exotoxins are then secreted into the surrounding medium during log phase.

example
Clostridium botulinum

Question 14

Endotoxin and fever reaction

Answer 14

1. Endotoxin (Lipid A of LPS)
2. Leukocytes release cytokines
3. TNF and IL-1 are released
4. FEVER
5. A macrophage ingests a gram (-) bacteria
6. The bacteria gets degraded in a vacuole, releasing endotoxins that induce the macrophage to produce cytokines (IL-1, and TNG-alpha)
7. The cytokines are released to the bloodstream by the macrophages, through which they travel to the hypothalamus (the temperature control center of the brain)
8. The cytokines induce hypothalamus to produce prostaglandins to produce higher temperature = fever.

Question 15

Which section of the LPS is embedded into the outer membrane of the bacteria?

Answer 15

Lipid A is embedded into the outer membrane, while the core polysaccharide and O polysaccharide are extended.

Question 16

Which type of toxin is usually more localized?

Answer 16

Exotoxins

Question 17

Exotoxin Domain
-what are they?
-mechanism of action?

Answer 17

Many exotoxins are two-domain (A-B) toxins, where each domain has a specific role in the toxin’s mechanism of action. These domains are typically referred to as the A domain (active domain) and the B domain (binding domain).
A = mechanism of action
B = determines binding specificity to host cell.

mechanism of action

Binding: The B domain binds to a receptor on the surface of a host cell.
Internalization: The toxin is taken into the cell, via endocytosis. The B domain facilitates the translocation of the A domain into the host cell cytoplasm.
Activation: The A domain separates from the B domain (either by cleavage or conformational change) and becomes active, exerting its toxic effect on the host cell.
Toxic Effect: The A domain disrupts cellular processes, leading to symptoms of the disease.

Question 18

Neurotoxins are an example of what?
Provide an example of a bacteria

Answer 18

A-B exotoxin

Tetanus and Botulinum toxin: Blocks the release of acetylcholine, causing muscle paralysis.

Question 19

Enterotoxin are an example of what?
Provide an example of a bacteria

Answer 19

A-B exotoxin

V.cholera and E.coli - Causes massive fluid loss in the intestines (diarrhea) by disrupting ion channels

Question 20

Cytotoxin are an example of what? Provide an example of a bacteria

Answer 20

A-B Exotoxin
Diphtheria toxin: Inhibits protein synthesis in the host cell… Leading to cell death

Question 21

Exotoxins membrane-damaging toxins

Answer 21

Leukocydins damage membranes of neutrophils and macrophages

Hemolysins destabilized plasma membranes of RBC’s and other tissue cells

*Blood agar plates: Differential medium that supports the growth of a wide variety of bacteria. They are particularly useful for identifying hemolytic bacteria, based on their ability to break down red blood cells (RBCs). (Beta/alpha/gamma Hemolysis)

Question 22

The capsule is considered a virulence factor for what?
What does the capsule do?
Provide an example of a bacteria?

Answer 22

immune system evasion (antiphagocytic factors)

The capsule will inhibit phagocytosis by hiding the surface antigens (like LPS) or by molecular mimicry (“look like” host antigen to prevent immune response)
-(capsule, enzymes, toxins)

Streptococcus pneumoniae has a polysaccharide capsule that prevents phagocytosis by immune cells.

Question 23

Mechanisms for antiphagocytic factors- immune system evasion

Answer 23

This is a virulence factor that may increase the virulence of a bacteria

-(capsule, enzymes, toxins)

mechanisms
-adapting to harsh environment of phagolysosome or neutralizing its hydrolytic enzymes.
-blocking fusion of lysosome w/n the phagolysosome
-escaping phagosome and living in phagocytic cell
-release toxins that kill phagocytes

Question 24

C5a Peptidase is considered a virulence factor for what?

Answer 24

C5a peptidase is a virulence factor produced by certain pathogenic bacteria, notably Streptococcus pyogenes (Group A Streptococcus). Its main role is to degrade and inactivate C5a, a component of the complement system, which is an essential part of the host’s innate immune defense.

Complement system= enhance phagocytosis, inflammation (mast cell- histamine), and lysis of foreign cells

Question 25

Siderophores is considered a virulence factor for what? What’s its mechanism?

Answer 25

**nutrient acquisition** (diverse enzymes, iron-binding proteins) Some pathogens produce enzymes that break down host molecules to acquire nutrients. *Example: Staphylococcus aureus produces hemolysins that lyse red blood cells to obtain iron.* Siderophores are specialized molecules produced by bacteria that play a crucial role in iron acquisition/iron stealing/iron thieve Iron is an essential nutrient for both pathogens and host organisms, but in biological systems, free iron is often scarce due to its sequestration by proteins like **transferrin** and **lactoferrin** in humans. Siderophores help bacteria overcome this limitation by scavenging iron from the host environment and making it available to the pathogen. Therefore siderphores contain a -lactoferrin-binding protein -transferrin-binding protein **mechanism** *Secretion*: The bacterium secretes siderophores into the environment. *Iron Binding*: Siderophores bind free iron or strip iron from host iron-binding proteins like transferrin, lactoferrin, or ferritin *Transport*: The iron-siderophore complex is recognized by specific receptors on the bacterial surface, allowing it to be imported into the bacterial cell. *Release*: Inside the cell, iron is released from the siderophore and made available for essential biological processes.

Question 26

sIgA protease is considered a virulence factor for what? and its mechanism?

Answer 26

**immune system evasion** sIgA protease is an enzyme produced by certain pathogenic bacteria that cleaves and inactivates secretory immunoglobulin A (sIgA), a key component of the host's immune defense, particularly at mucosal surfaces. This enzyme allows bacteria to evade the host immune system and establish infections, especially in mucosal areas such as the respiratory, gastrointestinal, and genitourinary tracts. Prevents opsonization of pathogens **mechanism** *Cleavage of sIgA*: sIgA protease specifically cleaves the hinge region of secretory IgA, separating its Fab and Fc fragments. This action reduces the ability of sIgA to bind to pathogens and neutralize them. *Immune Evasion*: By cleaving sIgA, bacteria can evade the host's immune defenses at mucosal surfaces, where sIgA normally prevents colonization and infection.

Question 27

What are Superantigens and their mechanism

Answer 27

Superantigens are a class of antigens that provoke an intense immune response by indiscriminately activating a large number of T-cells, bypassing the normal antigen processing and presentation mechanism. Unlike conventional antigens that require specific recognition by T-cell receptors, superantigens trigger a massive and nonspecific T-cell activation, leading to an excessive release of cytokines and causing immune system dysregulation. **Superantigens are potent immune system activators that lead to massive, non-specific T-cell activation and cytokine release.** **mechanism** *Normal Antigen Presentation*: In a typical immune response, an antigen is processed by antigen-presenting cells (APCs) and presented on MHC class II molecules to T-cell receptors (TCRs) on CD4+ T-cells. This interaction is highly specific, activating only a small subset of T-cells. *Superantigen Activation*: Superantigens, however, bind outside the usual antigen recognition site, forming a bridge between MHC class II molecules on APCs and T-cell receptors. This non-specific binding can activate up to 20-30% of the body's T-cells (compared to 0.01% in a typical immune response). Their ability to trigger a harmful immune response contributes to the severity of diseases such as toxic shock syndrome

Question 28

Ways to evade recognition from host immune response

Answer 28

**antigenic masking**: pathogen covered in host factors to avoid immune detection **antigen mimicry** **antigen variation** *The capsule will inhibit phagocytosis by hiding the surface antigens (like LPS) or by molecular mimicry (“look like” host antigen to prevent immune response)*