Module 12: Bacterial Pathogenesis (S. Pyogenes Case Study + Evolution)

Question 1

What TYPES of pathogens are S. pyogenes + M. tuberculosis?

Answer 1

S. pyogenes = Extracellular opportunistic pathogen

M. tuberculosis = An intracellular primary pathogen

Question 2

Where does S. pyogenes colonize humans?

Answer 2

Colonizes the pharynx mainly! (in 10-15% of people)

–> Can also colonize the skin and vagina

Question 3

What is meant by S. pyogenes being “opportunistic”?

Answer 3

The bacterium colonizes humans, often producing no clinical signs until it gains an opportunity to enter into host tissues leading to infection

“a disease waiting to happen”

Question 4

What predisposing conditions can enhance the risk of S. pyogenes infection?

Answer 4

1) Wounds

2) Weakened immune system

3) Poor Circulation

Question 5

LIST the diseases caused by S. pyogenes (DIRECTLY)

Answer 5

1) Cellulitis
2) Erysipelas
3) Necrotizing Fasciitis
4) Pharyngitis/Tonsilitis
5) Scarlet Fever
6) Septicemia

Question 6

List the diseases caused by S. pyogenes SEQUELAE

Answer 6

1) Rheumatic Heart Disease + Fever

2) Glomerulonephritis

Question 7

Cellulitis

Answer 7

Inflammation of deep tissues

Question 8

Erysipelas

Answer 8

Delineated infection of the DERMIS (can lead to cellulitis)

Question 9

Impetigo

Answer 9

Contagious, spreading infection of the skin

Question 10

Necrotizing Fasciitis

Answer 10

Necrotic destruction of tissue spreading along the fascia layer covering muscle

Question 11

Pharyngitis/Tonsilitis

Answer 11

Contagious infection of throat/tonsils characterized by intense inflammation + pus-filled nodules

Question 12

Scarlet Fever

Answer 12

Diffuse red skin rash

Question 13

Septicemia

Answer 13

(NOT exclusive to S. pyogenes)

Infection in the bloodstream

Question 14

What are the main attachment factors of S. pyogenes?

Answer 14

1) Fimbriae

2) Other surface components that attach to HOST fibronectin + collagen

Question 15

M Protein

Answer 15

Component of S. pyogenes fimbriae that allows for cell aggregation == allowing for the formation of microcolonies!

Question 16

How many different types of M protein are there? What does this mean for infection?

Answer 16

> 150 distinct M proteins

== Abs made against one will likely not work for another SO reinfection by S. pyogenes strains with different M proteins is very likely

Question 17

Pharygitis and Tonsilitis is usually ___________ because the body makes ___________ against ________

Answer 17

Pharygitis and Tonsilitis is usually “self-limiting” because the body makes IgAs + IgGs against the M protein

Question 18

How can pharyngitis/tonsilitis become serious?

Answer 18

Two ways:

1) S. pyogenes makes it into the bloodstream == SEPTIC SHOCK occurs

2) S. pyogenes sequelae

Question 19

Sequelae

Answer 19

Damage INDIRECTLY resulting from an infection that occurs AFTER an infection has been cleared!

(thought to be immune mediated)

Question 20

Rheumatic Heart Disease may be due to…

Answer 20

Antibody cross-reaction!

–> Due to cross reaction of Abs made against S. pyogenes M protein and heart muscle myosin

Question 21

What is a potential issue with antibodies made against S. pyogenes M protein?

Answer 21

They mat attack heart muscle myosin!

Because M protein and myosin have very similar AA sequences!

Question 22

What is glomerulonephritis?

What potentially causes it?

Answer 22

An inflammatory disease of the glomerulus

–> Potentially caused by complexes of S. pyogenes antigens and human Abs that get stuck + accumulate within the kidneys

Question 23

What toxins are extensively produced within S. pyogenes strains causing necrotizing fasciitis?

Answer 23

Pore-forming cytolysins

(Streptolysin S and Streptolysin O)

Question 24

What are 3 substances produced by S. pyogenes aiding in its evasion of the immune system?

Answer 24

1) “Self”-mimicked capsule

2) M protein

3) Enzymes

Question 25

How does the S. pyogenes capsule aid in immune evasion?

Answer 25

The capsule is made of host-like Hyalauronic acid (a substance recognized as "self" by the immune system) --> **Decreases opsonization and deters phagocytosis**

Question 26

How does the S. pyogenes M protein aid in immune evasion?

Answer 26

M protein binds antibodies BACKWARDS! (to the end usually bound to by TCRs! (Binds to the Fc region (base) rather than the arm region) --> = prevents immune cell recognition of the bound Abs!

Question 27

How does the S. pyogenes produced enzymes aid in immune evasion?

Answer 27

S. pyogenes produces enzymes that degrade host IgG and IgAs == decreasing the antibody response!

Question 28

What is the major distinguishing factor between pathogenic and non-pathogenic variants?

Answer 28

The presence of genes for VFs

Question 29

Horizontal Gene Transfer

Answer 29

The transfer of genetic material from organism to organism via: 1) Temperate Phage 2) Conjugation 3) Transposable Elements 4) Plasmids

Question 30

Pathogenicity Islands (PAIs)

Answer 30

Large stretches of DNA commonly found in pathogenic strains but NOT in the non-pathogenic relatives!

Question 31

PAIs typically contain genes encoding for...

Answer 31

1) Adhesion/invasion molecules 2) Toxins 3) Type III + IV secretion systems 4) Proteins facilitating metabolism (Ex: siderophores)

Question 32

Genes for VFs are often found...

Answer 32

CLUSTERED in PAIs!

Question 33

What are the common features of PAIs?

Answer 33

1) Abnormal GC content 2) PAI region flanked by direct repeat regions 3) Contain multiple mobile genetic elements (phage genomes + insertion sequences) 4) Contains genes encoding for ENZYMES needed for the movement + integration of DNA (integrase + translocase) 5) Adjacent to tRNA genes (common site for phage integration

Question 34

What are direct repeat regions used for?

Answer 34

Used for INSERTION by transposable elements

Question 35

Enzymes needed for the movement + integration of DNA

Answer 35

Integrase + Translocase