Extracellular Pathogens

Question 1

What are the characteristics of pathogens?

Answer 1

-infections cycles- routes of transmission
-Virulence factors- causing disease
-Adherence- attaching to cells
-Exotoxins: secreted toxins that kill host cells and endotoxins: proteins in the cell membrane (LPS) that are harmful to the host

Question 2

What are the four infection cycles?

Answer 2

-Direct horizontal transmission: direct contact (sneezes)
-Indirect horizontal transmission: vehicle transmission (food, water, fomites (dry surfaces))
-Vertical transmission: Mother passes to the fetus
-Arthropod vectors: passed on from ticks and mosquitos or exposure to feces.

Question 3

What are the three major groups of exotoxins?

Answer 3

-membrane disrupting: insert pores and other proteins into the host cell membrane
-Protein synthesis disrupting: inhibit key protein synthesis
-Signal transduction disrupting: alter cell signaling

Question 4

What is the exotoxin structure?

Answer 4

-Many exotoxins have a similar structure (5 beta subunits and one A subunits like a flower)but with a diversity of function
-AB exotoxins have two protein subunits (A and B)
-A: causes the toxic activity
-B: binds to host cell receptors

Question 5

What are the virulence factors of Cholera (how does it make you sick)?

Answer 5

-Flagella: have a single polar flagellum that allow the bacteria to reach the mucosal surface
-Cholera Toxin (CT): exotoxin of AB type (flower structure)
-TCP pili: genes for TCP pili are co-regulated with CT genes. Allow V. cholerae to attach to host cells. Acts as a receptor for CTX phage (this is how it becomes pathogenic)

Question 6

Describe the entry of Cholera Toxin

Answer 6

-entry of cholera toxin is dependent on a specific receptor, monosialosyl ganglioside (GM1 ganglioside) present on the surface of intestinal mucosal cells.
-normally cells have only the disialosyl form on their surface
-to remedy this situation the bacterium produces an invasion, neuraminidase, during the colonization stage which degrades gangliosides to the monosialosyl form, the receptor for cholera toxin.

Question 7

What is the Cholera Toxin Mechanism?

Answer 7

-The B subunit binds to GM1 faciliating entry of the A subunit
-The A subunit is cleaved at a single disulfide bond into two peptides, A1 and A2
-A1 catalyzes hydrolysis of NAD and transfer of the ADP-ribose group to a regulatory subunit of several heterotrimeric G proteins locking GTPase activity
-This leads to the constitutive activation of adenylyl cyclase, the rapid elevation of cAMP levels, and the activation of cAMP-dependent protein kinase A
-cAMP-dependent protein kinase A activates proteins involved in the secretion of chloride ions, bicarbonate, and water