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The bacteria Streptococcus equi uses a hyaluronic acid capsule and antiphagocytic proteins as two main virulence factors that effectively resist its equine host’s phagocytic defense. BIO 495 Senior Seminar Sarah Sanders 12/2/2014

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Page 1: Thesis Presentation

The bacteria Streptococcus equi uses a hyaluronic acid capsule and antiphagocytic proteins as two main virulence factors that effectively resist its equine host’s phagocytic

defense.

BIO 495 Senior SeminarSarah Sanders

12/2/2014

Page 2: Thesis Presentation

Strangles• Respiratory infectious disease • Infects equines, causing abscesses• Transmitted through direct orIndirect contact with exposed horse

http://www.yourhorse.co.uk/upload/19292/images/Equine%20strangles.jpg

http://www.horsespirit5.com/StranglesHorse.gif

Complications – metastatic stranglesAbscesses spread throughout the body and can cause internal bleeding. Chance of death increases 40%.

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Streptococcus equi Bacteria

Gram – positive bacteria

Morphology: matt, mucoid, glossy

May possess a capsule which contributes to itsvirulence.

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Hyaluronic Acid Capsule

http://textbookofbacteriology.net/strep.fig2.jpeg

Hyaluronic acid – has operonFunctionProvide support, protectionfrom host’s immune systemMechanism:Thought to disguise presence by altering bacterialmarker.

Page 5: Thesis Presentation

In Vivo Pathogenicity and Resistance to Phagocytosis of Streptococcus equi Strains with Different Levels of Capsule

Expression, Anzai, et al (1999)

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Conclusions

• Hyaluronidase can effectively degrade HA capsule• Hyaluronic acid capsule is an important virulence factor and

contributes to bacterial survival and proliferation• Capsulated strains lead to more infectious sites, more

bacterial colonization, resistance to phagocytosis

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Host’s Defense: Complement System

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Antiphagocytic Proteins• The M (SeM) protein – surface protein, secreted by bacterial

cells.• Se18.9 – factor H binding protein. Thought to regulate factor 1

in the classical complement pathway. • Opsonin: a marker that attaches to surface of bacterial cell• Opsonization: process by which the opsonin attaches to the

neutrophil receptor in order to the neutrophil to engulf bacterial cell and phagocytosis to ensue.

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Inhibition of C3 Deposition on Streptococcus equi subsp. equi by M Protein: a Mechanism for Survival in Equine Blood, Boschwitz &

Timoney, (1994)

Comp. inactivatedComp.activated

Table 2: Effect of 6 Treatments on survival of strain CF32 after 3 hours incubationIn plasma and whole blood

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Inhibition of C3 Deposition on Streptococcus equi subsp. equi by M Protein: a Mechanism for Survival in Equine Blood, Boschwitz &

Timoney, (1994)Table 2: Effect of 6 Treatments on survival of strain CF32 after 3 hours incubationIn plasma and whole blood

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C3 Binding

Treatments + strain AmountOf C3 Binding

A) CF32 w/ MProtein specificigG

84.8 +/- 23.8

B) CF32 w/ antiM F (ab) fragments

83.4 +/-24.7

C) CF32 w/ normal igG

23.2 +/- 7.7

D) Strain 19 (M-) 90.5 +/-9.3 Figure 3: Transmission electron micrographs showing C3 binding differences between S. equi strains

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Conclusions Conclude that the M protein inhibits C3 binding or deposition

on cell surface• Less C3 binding less C3b binding protein less opsonization less phagocytosis by neutrophils increased bacterial survival and proliferation strangles

http://jem.rupress.org/content/198/7/1057/F7.large.jpg

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The Antiphagocytic Activity of SeM of Streptococcus equi Requires Capsule, Timoney et al, (2014)

Table 3: Median % survival range of S. equi strains in equine blood and neutrophil suspension

Conclusions:Strains CF32 and SF463 that had both the HA capsule and the M protein functioning survived better in both serums (blood and neutrophil suspension than did strains Lex90, Lex 93, Se 1-8and Se19 that had one or the other virulencefactor functioning.

Possibility that both virulence factors actually worktogether to create a bacterial defense webagainst the host’s phagocytic defense.

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Future Directions• Global impact of workhorses• Possible treatment options- Penicillin G, works in early stages of the disease, not as

effective in the latter stages- Treatment that would combat both virulence factors - Hyaluronidase as option that degrades hyaluronic acid- M protein?

Page 15: Thesis Presentation

http://thechronicleherald.ca/sites/default/files/imagecache/ch_article_main_image/articles/SCI_HORSES_PRESERVATION_1.JPG

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References• Anzai, T. et al. (1999). In vivo pathogenicity and resistance to phagocytosis of Streptococcus equi strains

with different levels of capsule expression. Vet. Microbiology, vol 67, 277-286 • Boschwitz, Jeffrey S. & Timoney, John F. (1994). Inhibition of C3 Deposition on Streptococcus equi subsp.

Equi by M Protein: a Mechanism for Survival in Equine Blood. Infection and Immunity. Vol 62, no 8. 3515-3520.

• Complement. (n.d.). Retrieved November 27, 2014, from http://222.197.192.76/jpkc/swjcjs/biosite/files/immunology/complement.html

• Gordon, D.L et al. (1988). Analysis of C3 Deposition and Degradation on Bacterial Surfaces after Opsonization. J. Infect. Dis. 157, 697-704

• The Complement System. (2014, April 17). Retrieved November 27, 2014, from http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/Complement.html

• Timoney, John F, et al. (2014). The Antiphagocytic Activity of SeM of Streptococcus equi Requires Capsule. Journal of Equine Science, vol 25 no 2. 53-56.