Bacterial Pathogenesis

Pathogen

an organism that causes disease

What are the five steps of pathogenesis?

1. Entry and attachment

2. Evasion of host defenses

3. Multiplication and spread

4. Damage

5. Transmission

What are some routes of entry for bacterium?

• ingestion (ex: salmonella)

• Inhalation (kennel cough, bovine respiratory disease)

• Transplacental (brucellosis)

• Vector-borne

Biological vector

pathogen replicates or develops inside the vector

What is an example of a biological vector?

Ixodid ticks with anaplasma marginale

Mechanical vector

carries the pathogen on its body with no development or replication on the vector

What is an example of a mechanical vector?

Face flies and moraxella bovis (pink eye in cattle)

Fomite

inanimate object that carries and agent from host to host

What is an example of a pathogen entering the body after trauma?

Foxtails and actinomyces

Iatrogenic

illness caused by medical examination or treatment

What is required for attachment of a bacterium?

bacterial adhesion and host receptor

Enterotoxigenic E. Coli use _____ for attachment.

Fimbriae

ETEC K99 (F5) affects what species?

Cattle

ETEC (F18) affects which species?

Porcine

What is true about the receptors of Enterotoxigenic E. Coli finbriae?

The receptors’ expression are age dependent and only show when a neonate.

What does enteropathogenic E. Coli use as an adhesion?

surface protein - intimin

True or False: EPEC inject their receptor into the host cell.

TRUE

Uropathic E. Coli use ___ for adhesions.

P-fimbriae

What does UPEC p-fimbriae attach to?

residues to lead to ascending infection

How can you block attachment?

• fimbrial vaccines

• Proacthocyanidins in cranberries

• Normal microbiota

The _____ immune response is present at birth

innate

The _____ immune response is developed in response to pathogens.

Adaptive

What are antimicrobial peptides (AMPs)?

non-specific host defense peptides that are produced at epithelial surfaces

What does Pseudomonas aeruginosa cause?

Equine Corneal Ulcers

How does Pseudomonas aeruginosa evade the host immune system?

cleave AMPs with Phosphlipase B (protease)

How does Staphylococcus aureus evade the host immune system?

repulses AMPs with staphylokinase neutralizing defensins and reducing the net negative charge of the bacterial envelope

How does Klebsiella Pneumoniae evade the host immune system?

shield surface with capsule against AMPs

What are Toll-like receptors?

pattern recognition receptors that identifies Pathogen Associated Molecular Patterns (PAMPs) and trigger cytokines release to start an inflammatory response

What is a consistent feature of bacterial infection?

changes in leukocytes

How can bacteria evade the TLRs? Give an example of each.

• Modify the PAMPHLET (cannot be identified): Leptospira & Campylobacter

• Block TLR signaling pathway: Brucella

How can bacteria evade phagocytosis?

• prevent chemotaxis

• Avoid opsonization

• Avoid ingestion

• Survive inside the cells

• Survive respiratory burst

What bacterium prevents cheomtaxis? How?

Pseudomonas aeruginosa

• hides its signal so cells cannot find it

What bacterium prevents phagocytosis via avoiding opsonization?

Staphylococcus aureus via protein A

What bacteria avoid ingestion (phagocytosis) and how? (Many)

• Klebsiella pneumonia & Rhodococcus equi: polysaccharide capsule

• Pseudomonas aeruginosa: alginate

• Streptococcus equi: hyaluronic acid capsule

What are the three ways bacteria survive inside the phagocytes cells?

• escape from phagosome into cytoplasm

• Prevention of phagocytes-lysosomal fusion

• Resistance to lysosomal enzymes

What bacteria evade phagocytosis by surviving inside the phagocytic cells via escaping the phagosome?

Listeria via Listerolysin O

What bacteria survive inside the phagocytic cells via escaping by preventing phago-lysosomal fusion?

• Mycobacterium spp

• Aspergillus flavus

• B. Abortus

• Chlamydia psittaci

What bacteria survive inside phagocytic cells by resisting lysosomal enzymes?

• Mycobacterium spp. (mycolic acid)

• Yersinia spp. (capsule)

True or False: An organism that survives inside a phagocytic cells via escaping gets free transport.

TRUE

What is respiratory burst?

oxygen dependent myeloperoxidase reactions used by macrophages to kill phagocytized bacterium

How does staphylococcus survive respiratory burst?

Catalase to break down H2O2

How does staphylococcus aureus survive respiratory burst?

Carotenoid pigment

What bacteria survive respiratory burst by inhibiting it?

Pasturella multocida and Histophilus somni

What is iron sequestration?

host defense against bacterial growth by using iron-binding proteins to manage free iron levels

What proteins are used to bind iron by the host?

• transferrin

• Lactose rein

• Haemoglobin

How do bacteria survive iron sequestration?

siderophores are secreted in low iron levels and competitively bind to the iron, stealing it from transferring and lactoferrin

How is the adaptive immune system countered by bacteria?

antigenic variation and antibody destruction

What is antigenic variation?

organism changes its surface antigens over time

What are two examples of antigenic variation?

• Campylobacter fetus venerealis: Bovine venereal campylobacteriosis persists in bull

• Anaplasma marginale: lifelong carrier

What bacteria destroy antibodies?

Histopholis Somnus & Streptococcus pneumoniae with IgA proteases

• prevent opsonization and Fc receptor-mediated phagocytosis

What explains host and tissue specificity?

Attachment

true or false: Bacterial infections always cause an increase in leukocytes.

FALSE. It always changes but can increase or decrease.

What sets the tempo of disease?

growth rate

How long is a routine culture?

24-48hrs

True or False: You do a routine culture and nothing grows. The patient does not have an infection.

FALSE could be a slow growing bacterium

What type of bacterium is reachable by antibody and complement?

Extracellular

Give two examples of extracellular bacterium.

• staphylococcus

• Streptococcus

Give an example of a bacterium that is intracellular in cytoplasm.

Listeria monocytogenes & Ricketsia

List examples of intracellular bacteria that live in the host’s cell’s vacuoles.

• Coxiella

• Brucella

• Salmonella

Give an example of an obligate intracellular bacterium.

Coxiella burnetii

True or False: Coxiella burnetii will grow on a routine culture plate

FALSE

List an example of a facultative intracellular bacterium

Listeria

How does listeria invade the cell?

internalins

How does listeria break the phagocytic vacuoles?

Listeriolysin

Example of a lophotrichous bacterium

heliobacter sp

Example of a peritrichous bacterium

Salmonella spp.

What is proteus mirabilis?

swarming motility observed in culture that can aid in spread in vivo

What are the tw categories of damage?

• direct

• immune mediated

Toxin

poisonous substances released by various pathogens

Endotoxins

remain inside or on the surface of the bacteria

Exotoxins

toxin secreted out of the bacteria

List some examples of exotoxins.

• neurotoxins

• enterotoxins

• exfoliative toxin

What type of bacteria commonly have endotoxins?

Gram negative bacteria

List two examples of bacteria that cause direct damage and how

• E. coli enterotoxins - act on intestinal enterocytes to cause secretory diarrhea

• Clostridium perfringens - phospholipase C damages cell membrane causes necrosis

• Clostridium tetani - Tetanospasmin blocks inhibition and leads to spastic paresis

• Clostridium botulinum - neurotoxin blocks Ach and causes flaccid paresis

Purpura Hemorrhagica

aseptic necrotizing vasculitis characterized primarily by edema and petechial or ecchymotic hemorrhage

What is the pathogenesis of purpura hemorrhagica?

vasculitis caused by deposition of immune complexes in blood vessel walls

What is sepsis and what is it caused by?

severe, whole body inflammatory response to bacteria

• response to bacterial components such as endotoxin lipopolysaccharide (LPS)

What are superantigens?

non-specific activation of T-cells that causes massive inflammation, multiorgan failure and death

What is the cause of toxic shock syndrome?

Staphylococcus aureus

What is the cause of equine strangles?

Streptococcus equi

Give an example of a bacteria that has minimal effect on the host.

Campylobacter fetus venerealis

Give an example of a bacteria that has major effect on host.

• Bordatella bronchiseptica

• Enterotoxigenic E. coli (calf scours)

• Bacillus anthracis

What is the purpose of spores for bacteria?

survival in response to adverse environmental conditions

What is a dead end host? Give an example.

end of transmission

• ex: lyme dz w/ dogs and humans

Zoonoses

can be transmited from animals to humans

WHat are fungal spores for?

reproduction