AH 3320 Q6: Virulence and Pathogenicity

What are the 6 steps of common sequence in pathogenesis of infectious diseases?

EAMIED

1. Entry of pathogen → body

2. Attachment of pathogen → body tissues

3. Multiplication of pathogen

4. Invasion/spread of pathogen

5. Evasion of host defenses

6. Damage → host tissue(s)

What are 6 portals of entry?

PIIIEE →

• Penetration → skin/mucous membranes

• Inoculation (arthropod) → tissues (wounds, insect bites)

• Inhalation (respiratory tract)

• Ingestion (GI tract)

• Entry → genitourinary = urinary + reproductive

• Entry → blood (transfusion, IV drug abuse)

What are the 6 I’s of portals of entry?

• Ingestion → GI tract

• Inhalation → respiratory tract

• IV → blood/tissue

• Inoculation → wound/bite → tissue

• lntercourse → urogenital

• Iatrogenic → surgical sites, blood, respiratory, GI, UTI

What are the 6 areas that pathogen portals of entry can affect?

• Respiratory tract

• Blood & Vector-borne

• Urogenital tract

• Ocular Surface

• Gastrointestinal Tract

• Skin

What are 4 mechanisms of pathogen adhesion?

What does it must have?

• Fimbriae

• Capsules

• Spikes

• Hooks/flagella

Adhesin

What are 2 ways a pathogen can multiply?

• Multiply in one location

• Multiply throughout body

Through what process do bacteria replicate?

Through what process do viruses replicate?

Through what process do worms replicate?

• Bacteria → fission

• Viruses → Budding + Lysis

• Worms → egg laying

How many cells grow after 10 hours of bacterial growth?

>1 billion cells

_________ pathogens have evolved wide range of strategies to colonize + invade human organisms, despite presence of multiple host defense mechanisms.

Bacterial

What are 3 areas that pathogenic bacteria can invade or spread to?

SII

• Surface of host cells

• Inside host cells

• Cross epithelial/endothelial host barriers → Internal tissues

  • Severe diseases

What are 3 examples of gastrointestinal pathogens?

Salmonella

Shigella

Listeria

• GI tract → replicate → increase likelihood of causing disease

How does the host counteract pathogens?

What is antigenic variation?

How does this relate to the flu vaccine?

Antigenic variation = method used by pathogens → evade immune system by Δsurface antigens

• Inhibit phagocytosis

• New Flu vaccine each year → constantly changing way it looks

What is camouflage and molecular mimicry?

What is 1 example?

Molecular mimicry = organisms coat themselves w/ host proteins → conceal foreign identity

• Adult schistosomes

What enzyme do some pathogens produce to destroy host’s antibodies?

IgA protease = enzyme destroys host’s antibodies

What is the major way that pathogens infect host cells to get infectious disease?

Damaging host

What is 5 characteristics direct damage to host tissue(s)?

• Pathogen growth in host cells → lysis

• Toxins

• Enzymes

• Disrupt host cell function

• Waste product production

What are 3 characteristics of indirect damage to host tissue(s)

Immune system mistakenly destroys normal cells in process of fighting foreign cells

• Innocent bystander = immune mediated destruction

• Induce hypersensitivity reactions

• Use host nutrients (Fe)

What are 7 tissues that can be damaged?

What is the difference between symptoms & signs?

Tissues:

• Neurologic

• Renal

• Hepatic = liver

• Gastrointestinal

• Thromboembolism = blood clot

• Cardiac

• Endocrine

• Dermatological

Symptoms = Unmeasurable = Dizziness, headaches

Signs = Measurable = Elevated enzymes, elevated bilirubin

All infections go through 6 steps: (True/False)

FALSE → some exotoxin-producing intestinal pathogens go right to damage to host tissue(s)

• Do NOT always need attachment or invasion of tissues

• Some exotoxin-producing intestinal pathogens → cause disease (W/O adhesion/attachment to/invasion of tissue)

What are enterotoxins?

Enterotoxins = attack GI cells → small intestine

What is the difference b/w virulent and avirulent strains?

Virulent strains = capable of causing disease

Avirulent strains = are NOT capable of causing disease

What are 2 ways capsules used to infect host cells?

Capsules = protect bacteria from host; sometimes used to adhere to host cells

What is 2 conditions does S. pharyngitis cause?

Which strain is more virulent and why?

Pharyngitis = swelling of pharynx

Flesh-eating bacteria

S. Pharyngitis → flesh eating bacteria

• Produce certain enzymes = more virulent than other strains

What is virulence?

Virulence = degree of pathogenicity

How does shigella and salmonella demonstrate virulence?

Which is more virulent? Why?

Shigella → 10 Shigella cells → shigellosis

Salmonella → 100-1000 Salmonella cells → salmonellosis

Shigella = more virulent → more likely to cause disease

Strains that produce toxins are more/less virulent that strains that do not produce toxins

MORE

What are virulence factors?

Virulence factors = phenotypic characteristics dictated by organism’s genotype → microbes = virulent

• Surface molecule of host cells

• Recognized by pathogen → adhere to receptor (integrin)

What must many pathogens do to cells after entering body?

MUST ANCHOR themselves to cells → can multiple + invade

Why can some viruses cause respiratory infections?

Can recognize + adhere to host receptors (integrins) on respiratory cells

What protein allows influenza virus to attach to respiratory cells?

What is the name of the receptors?

Hemagglutinin protein

Receptors = integrins

What protein allows coronavirus to attach to respiratory cells?

What is the name of the receptors?

Spike (S) protein

ACE2 receptors = integrins

Are adhesins considered virulence factors?

YES → allow pathogens to attach to host cells

What are Pili or fibriae?

Pili (bacterial fimbriae) = virulence factors = enable bacteria to attach to surfaces (cells + tissues in body

What leads to urethritis?

What are non-piliated strains that cannot adhere called?

Pili attachment to urethra → urethritis

Avirulent strains

Why are capsules an example of virulence factors?

Capsules = anti-phagocytic function

• Phagocytes unable to attach to molecules on bacteria (encapsulated → protected from being destroyed by host cells)

What virulence factor does S. pneumoniae, Klebsiella, and meningitis use?

Capsules

What are flagella?

How are they an example of virulence factors?

Flagella = allow bacteria to invade aqueous areas of body + escape phagocytosis

Where are phagocytes typically present?

Bloodstream → help destroy pathogen

Pili (fimbriae), capsules, and flagella (DO/DO NOT) explain how pathogens cause disease

DO NOT

What major virulence factor by which pathogens cause disease?

• Toxins

• Exoenzymes

What are 7 examples of exoenzymes released by bacteria?

• Necrotizing enzymes = destruction of cells + tissues

• Coagulase = blood clot

• Kinases = hijack signaling

• Hyaluronidase = damage hyaluronic acid

• Collagenase = damage collagen

• Hemolysins = damage RBCs + other cells

• Lecinthase = damage cells

What do necrotizing enzymes cause?

Necrotizing enzymes = destruction of cells + tissues

What do coagulase cause?

Coagulase → clotting (protection from host/immune defense mechanisms)

What do kinases cause?

Kinases → dissolve clotsS

What is streptokinase (SK)?

Streptokinase = bacterial protein produced by B-hemolytic streptococci

• Forms “activator complex” → converts inactive plasminogen → active plasmin

• Degrade fibrin clots + fibrinogen

What are uses of streptokinase?

• Treatment of thromboembolic disorders

  • Lysis of pulmonary emboli

  • Arterial thrombus

  • Deep vein thrombus

  • Acute artery thrombosis

What are 4 examples of exoenzymes released by bacteria?

Hyaluronidase = dissolves hyaluronic acid (=cement that holds tissue cells together)

Collagenase = dissolves collagen (supportive, structural protein)

Combined = allows pathogens to invade deeper → cells/tissues

Hemolysins = toxin → disrupt cell membrane → lysis

Lecinthinase = toxin → disrupt cell membrane → lysis

How are hyaluronidase and collagenase used to help invade internal tissues?

• Hyaluronidase = targets hyaluronic acid = glue-like substance that cements cells to ECM

  • Allow bacteria to spread → deeper tissues

• Collagenase = targets collagen = tough, fibrous protein → structural strength to muscles, tendons, organs, skin

  • Allow bacteria to move across barriers → deeper tissues

What is the difference between hemolysins and lecithinase?

Hemolysins = damage/lyse RBCs

Lecithinase = destroy host cell membrane/phospholipids (RBCs + other cells)

What host nutrient does pathogen use to cause indirect damage?

Iron (Fe)

What are toxins?

What are the 2 types?

Toxins = poisonous substances released by various pathogens → damage host tissues + cause disease

• Endotoxins = lipopolysaccharides of cell wall of Gram-negative bacteria (pink)

  • Serious, adverse effects (fever, shock)

  • Toxin = pyrogenic (causes fever)

• Exotoxins = produced within cell → released from cells

What is the 3 major differences between gram-positive and gram-negative bacteria?

Gram-positive = purple

• Peptidoglycan layer = THICK

• Outer membrane = absent

• Produce = exotoxins (but not always)

Gram-negative = pink

• Peptidoglycan layer = thin

• Outer membrane = PRESENT (LPS)

• Produce = endotoxins

What is the most potent exotoxin?

Neurotoxins = effects on neurological system

• Spastic, rigid, muscle contraction

• Tetanus

What tract do enterotoxins affect?

What is an example of an infection that does this?

What is the key characteristics of C. difficile?

GI tract

C. difficile

Pseudomembranous colitis (PMC) = yellow plaque in colon

What type of disease do erythrogenic toxins cause?

Scarlet fever

• one of complications of untreated strep throat

What is the 5 major differences b/w exotoxins and endotoxins of bacteria?

Exotoxins

• Produced by Gram-positive

• Peptidoglycan @ specific sites

• Characteristic diseases

  • Diphtheria

  • Tetanus

Endotoxins

• Produced by Gram-negative

• Lipopolysaccharides act throughout body

• Fever, weakness, aching

  • Typhoid fever

  • Meningitis

What is the major difference between endotoxins and exotoxins?

What are 8 types of exotoxins?

Endotoxin = released from Gram-negative bacterial cell walls

Exotoxin = produced within cell → released from cell

• Neurotoxins = damage to CNS

• Enterotoxins = damage to GI

• C. difficile = pseudomembranous colitis

• S. aureus = toxic shock syndrome

• Exfoliative toxin = scalded skin syndrome

• Erythrogenic toxin = scarlet fever

• Diphtheria toxin = diphtheria

• Leukocidins = damages leukocytes

What are _ examples of virulence factors?

• Fimbriae

• Capsules

• Flagella

• Toxins

  • Endotoxins

  • Exotoxins