5. B. pertussis

B. Pertussis

Causative agent of whooping cough

B. Pertussis target

Strict human pathogen, can cause severe disease

B. Pertussis replication

Known to survive and replicate inside of amoebas

Pseudogenes

Genes that have mutated to be no longer functional

B. Pertussis adhesins

Filamentous hemagglutinin (FHA)

Fimbriae

Pertactin

Filamentous haemagglutinin adhesin

Large filamentous protein that adheres to host epithelium in respiratory tract. Biofilm formation

Fimbriae

Allows binding to tracheal epithelial cells via sugars, heparin and integrin

Pertactin

Binds to ciliated tracheal epithelium

Pili and fimbriae

Can play a role in motility and adhesion

B. Pertussis virulence- toxins

Tracheal cytotoxin (TCT)

Dermonecrotic toxin (DNT)

Pertussis toxin (PT)

Adenylate cyclase toxin

Tracheal cytotoxin (TCT)

Cell wall peptidoglycan fragment, usually recycled by bacteria

What does TCT do to host?

Stops cilia from beating and causes epithelial cell death, so cilia cannot clear lung debris AND causes coughing fits

Dermonecrotic toxin (DNT)

Causes necrotic skin lesions and is lethal

Pertussis toxin (PT)

increases cAMP and decreases neutrophil recruitment and immune response

Why is increased cAMP bad for the cells?

Increases host apoptosis and decreases immune system response

Pertussis toxin is what type of toxin

AB5 exotoxin

AB5 toxin

Has 5 b subunits for every 1 A subunit

Adenylate cyclase toxin (ACT)

Increases cAMP and forms pores in host cells leading to cell death

ACT is what type of toxin

Rtx toxin

Rtx toxin

Pore forming toxin

Cell death from TCT, DNT, and ACT

Causes tracheal swelling and difficulty breathing- CAUSES WHOOPING

How are B. Pertussis toxins regulated

Two component systems

TCS- Sensor

Membrane bound histidine kinase (HK) to sense signal

TCS- Regulator

Response regulator which is phosphorylated by HK to activate and perform cellular function

BvgAS

TCS required for nearly all B. Pertussis virulence expression

BvgS

HK which starts a phosphorelay to activate response regulator BvgA

BvgA

Response regulator of BvgAS TCS

B. Pertussis virulence factors- regulators

BvgAS which controls expression of virulence factors

How does the PT toxin work

ADP-ribosylates G protein, preventing blockage of Adenylate cyclase causing excess cAMP production

Bordadella is autotrophic for

Nicotinic acid