4. Diptheria

Pseudomembrane

Thick grey coating that forms at the back of the tr=hroat, eventually suffocates

2 main virulence factors of C. diphtheriae

Adhesins
Exotoxin

Adhesins

attachment to host cells

Exotoxin

causes most infection symptoms

Adhesion of c. diptheriae

Mediated by surface pili that bind to host pharyngeal cells

Pili vs fimbriae

pili are longer and less numerous, both used for motility and adhesion

C. diptheriae pili

Made up of 9 spa proteins, SpaABC

MSCRAMMS proteins

mediate atatchement to fibrinogen and collagen of the host

Exotoxins are

secreted accross cell membrane, NO LYSIS

endotoxins

Part of bacterial membrane, only released during pathogen lysis

Only knows endotoxin

as lipopolysaccharide, which triggers inflammatory responses in the host from gram neg bacteria

AB toxins

have 2 subunits that break apart after entry into host cells

B subunit of AB toxin

binds to host cell

A unit of AB toxin

escapes into host cytoplasm to cause toxic effects

What type of toxin is the diptheria toxin

AB exotoxin

Diptheria toxin entry into host cells

B subunit binds to host cell, then toxin is taken in via endocytosis

Diptheria A subunit

leaves NAD and adds an ADP-ribose moiety to elongation factor 2 (EF-2), making it inactive (This is called ADP-ribosylation)

Result of ADP-ribosylation

is the inhibition of protein synthesis in host cells, leading to cell death.

NAD

electron carrier during cellular respiration

Overall what does the diptheria toxin do?

removes the ADP-ribose from NAD and transfers it to EF-2

EF-2

functions to translocate the ribosome to the next codon (A site to P site) during protein synthesis, essential for elongation.

How is diptheria toxin regulated

when iron is low in the environment, the expression of the toxin gene is increased by removing DtxR from the repression of the gene.

When would iron be low

When pathogen is INSIDE THE CELL (needs to kill cell to get iron)

HIgh iron condition

dtxR binds to iron and binds to promoter to block transcription of toxin

Low iron condition

dtxR is released from the promoter, allowing transcription of the diphtheria toxin gene to proceed.

Master regulator for diptheria toxin

dtxR regulates in response to iron availability