MCB Chapter 15: Microbial Mechanisms of Pathogenicity

Define Pathogenicity

the ability to cause disease

Define Virulence

the degree of pathogenicity

What are the portals of entry?

• Mucous membranes

• skin

• parenteral route

  • deposited directly into tissues when barriers are penetrated

What is true about most pathogens and portals of entry?

Pathogens have a preferred portal of entry

What is ID₅₀?

Infectious dose of 50% of a sample population in which measure virulence of a microbe

What is LD₅₀?

lethal dose for 50% of a sample population in which measures potency of a toxin

What is the ID₅₀ for skin?

10-50 endospores

What is the ID₅₀ for inhalation?

10,000-20,000 endospores

What is the ID₅₀ for ingestion?

250,000-1,000,000 endospores

What is the LD₅₀ in Botulinum?

0.03 ng/kg

What is the LD₅₀ for Shiga toxin?

250 ng/kg

What is the LD₅₀ for Staphylococcal enterotoxin?

1350 ng/kg

What is adherence?

almost all pathogens attach to host tissues

What is the role of Adhesins (ligands) during adherence?

bind to receptors on the host cells

ex: glycocalyx or fimbriae

What do microbes do for adherence?

form biofilms (communities that share nutrients)

Describe capsules in adherance.

Glycocalyx is around the cell wall

What are the different capsules that impair phagocytosis?

Streptococcus pneumoniae: pneumonia

Haemophilus influenzae: pneumonia and meningitis

Bacillus anthracis: anthrax

Yersinia pestis: plague

What do M proteins do for the cell wall in virulence?

• resists phagocytosis

  • Steptococcus pyogenes

What do Opa proteins do for the cell wall for virulence?

• allows attachment to host cells

  • Neisseria gonorrhoeae

What does Waxy lipids (mycolic acid) do for cell walls in virulence?

What does Coagulases enzyme do in virulence?

coagulate fibrinogen

(coagulate: changing from liquid to semi-solid/ solid)

What does Kinases enzyme do in virulence?

digest clots

What does Hyaluronidase enzyme do in virulence?

digests polysaccharides that hold cells together

What does Collagenase enzyme do in virulence?

breaks down collagen

What does IgA proteases enzyme do in virulence?

destroy IgA antibodies

What is antigenic variation?

pathogens alter their surface antigens (and antibodies and rendered ineffective)

(antigen: any substance, such as bacteria, viruses, toxins, or foreign proteins, that causes your immune system to produce antibodies against it)

What are Invasins in penetration into the host?

Surface proteins produced by bacteria that rearrange actin filaments of the cytoskeleton

• cause membrane ruffling

What is the role of actin in penetration into the host?

move from one cell to the next

• Shigella and Listeria

Describe the survival inside phagocytes?

• requirement for low pH in phagolysosome

• Escape from phagosome before lysosomal fusion

• Prevention of fusion of lysosome with phagosome

What is the role of biofilms in phagocytosis?

• evading phagocytes

• bacteria are more resistant to phagocytosis, shielded by extracellular polymeric substance (EPS) of it.

What is Siderophores?

using the host’s nutrients

they are proteins secreted by pathogens that bind more tightly than host cells

What is requires for Siderophores?

iron

What is the affect of direct damage?

• disrupts host cell function

• uses host cell nutrients

• produces waste products

• multiplies in host cells and causes ruptures

Define toxins.

poisonous substances produces by microorganisms

• produce fever, cardiovascular problems, and diarrhea, and shock

Define Toxigenicity.

ability of a microorganism to produce a toxin

Define Toxemia.

Presence of toxin in the host’s blood

Define Intoxications.

presence of toxin without microbial growth

What happens when proteins are produces and secreted by bacteria?

• soluble in bodily fluids; destroy host cells and inhibit metabolic functions

• A-B toxins contain an enzyme component (A part) and a binding component (B part)

  • Diphtheria toxin

What are Genotoxins?

damage DNA (causing mutations, disrupting cell division, leading to cancer)

What are Antitoxins?

antibodies against specific exotoxins

What are Toxoids?

inactivated used in vaccines

Describe the A-B Exotoxin Process?

1. Bacterium produces and releases the A-B toxin

2. B (Binding) component of exotoxin attaches to host cell receptor

3. The plasma membrane of the host cell invaginates (folds inward) at the point where the A-B exotoxin and plasma receptor make contact. The exotoxin enters the cell by receptor-mediated endocytosis

4. A-B exotoxin and receptor are enclosed in pinched-off portion of plasma membrane during phagocytosis

5. A-B components of exotoxin separate. The A component alters the host cell function, often by inhibiting protein synthesis. The B component is released from the host cell, and the receptor is inserted into the plasma membrane for reuse.

What are exotoxins?

Membrane-disrupting toxins lyse host cells by disrupting plasma membranes, proteins produced inside pathogenic bacteria, mostly part of gram-positive bacteria, exotoxins are secreted into the surrounding medium during the log phase

What do Leukocidins do?

kill phagocytic leukocytes

What do Hemolysins do?

Kill erythrocytes by forming protein channels

What do Streptolysins do?

Hemolysins produces by streptolysins

What do Superantigens cause?

an intense immune response due to release of cytokines from host cells (T cells)

What symptoms does Superantigens cause?

fever, nausea, vomitting, diarrea, shock, and death

What disease are caused by exotoxins?

nBotulism, Tetanus, Diphtheria, Scalded skin syndrome, Cholera, Traveler’s diarrhea, Anthrax, Gastric cancer, Skin and soft tissue infection, Gas gangrene and food poisoning, antibiotic-associated diarrhea, food poisoning, toxic shock syndrome

What are endotoxins?

Lipid A portion of lipopolysaccharides (LPS) of gram-negative bacteria

Released during bacteria multiplication and when gram-negative bacteria die

• Stimulate macrophages to release cytokines

• Cause disseminated intravascular coagulation

What is the Pyrogenic Response?

1. A macrophage ingests a gram-negative bacterium

2. The bacterium is degraded in a vacuole, releasing endotoxins that induce the macrophage to produce cytokines, interleukin-1 (IL-1), and tumor necrosis factor alpha (TNF-α)

3. The cytokines are released into the blood-stream by the macrophages, through which they travel to the hypothalamus, the temperature control center of the brain

4. The cytokines induce the hypothalamus, which reset the body’s “thermostat” to a higher temperature, producing fever.

What is Endotoxin detection?

Limulus amedocyte lysate (LAL) assay is used to test for endotoxins

• blood of horseshoe crabs contains amebocytes

• Amebocytes lyse in the presence of endotoxin, producing a clot

What do plasmids carry?

genes for toxins, production of antibiotics, and enzymes

What does Lysogenic conversion do?

changes characteristics of a microbe to incorporation of a prophage

What are cytopathic effects?

visible effects of viral infection on a cell

What are cytopathic effects?

• stopping cell synthesis

• causing cell lysosomes to release enzymes

• creating inclusion bodies in the cell cytoplasm

• fusing cells to create a syncytium (multiple nuclei)

• Changing host cell function or inducing chromosomal changes

• Inducing antigenic changes on the cell surface

• Loss of contact inhibition in the cell, leading to cancer

What are alpha and bets interferons?

• produced by virally-infected cells

• Protect neighboring cells from viral infection

  • inhibit synthesis of viral proteins and host cells proteins

  • kill virus-infected host cells by apoptosis

What is fungi?

• toxic metabolic products

• provoke an allergic response

• proteases modify host cell membranes

• capsules prevent phagocytosis

What is Trichothecene?

toxins inhibit protein synthesis

What is Ergot?

alkaloid toxins that cause hallucinations

What is Aflatoxin?

a carcinogenic toxin produced by Aspergillum

What is Mycotoxin?

produced by mushrooms and are neurotoxin

What are Phalloidin & amanitin?

produced by the mushroom known as the deathcap

What does protozoa cause

cause symptoms

protozoa avoid host defenses by:

• digesting cells and tissue fluids

• Growing in phagocytes

• Antigenic variation

What do Helminths do?

• use host tissue for growth

• produce large masses; cause cellular damage

• produce waste products

• produce waste products that cause symptoms

What do Algae do?

• Some produce a neurotoxin called saxitoxin

  • paralytic shellfish poisoning

What are the different portals of exit?

• Respiratory tract

  • coughing and sneezing

• Gastrointestinal tract

  • feces and saliva

• Genitourinary tract

  • urine; secretions from the penis or vagina

• Skin

• Blood

  • Arthropods that bite; needles or syringes

What is the purpose of antigenic variation?

They alter their surface proteins which allows them to evade a host’s immune system