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Streptococcus pyogenes: disease and molecular pathogenesis 2

Part 2 of 2
Published on March 31, 2026   33 min

A selection of talks on Clinical Practice

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0:05
I'd like to briefly review the complement pathway. It's so important for understanding the pathogenesis of Streptococcus pyogenes and actually quite a few other bacterial pathogens. In a non-immune animal, the alternative pathway is critical for providing effector molecules that remove bacteria from tissue. In an immune animal, the classical pathway is activated by antibody-antigen reactions. There are several important molecules generated by the proteolytic cleavage of complement proteins in our blood. One of the most important is C3b. It's an opsonin. It butters up bacteria so they can be recognized by complement receptors on phagocytic cells. C5a is the chemotaxin that attracts phagocytes such as PMNs or macrophages very early in an infection. Obviously, both of these molecules are critical for removing bacteria from tissues. If the bacterium is a gram-negative bacterium, the complement system ultimately produces a complex called the membrane attack complex. This inserts holes in the outer membrane of gram-negative bacteria. The membrane attack complex has really no effect on gram-positive bacteria, which lack an outer membrane.
1:32
As I stated, C5a is an important product of the complement activation. It's the earliest signal to attract phagocytic cells to a site of infection. IL8 is another chemotaxin that's important. It's produced somewhat later by inflammation. Both chemotaxins recruit PMNs and macrophages locally to clean up foreign microbes before infection progresses. The C5a peptidase or SCPA is produced by all M types of S. Pyogenes and human isolates of Streptococcus agalactiae, group C streptococci, and group G streptococci. Cow, pig, and horse isolates genetically lack the protease. S. Pneumoniae also produces a related but different protease. Strep also produces an IL8-specific protease called SpyCEP. It's not produced by all M types of S. Pyogenes. Both proteins are highly conserved, and both are candidates for vaccine development. The reference listed on the slide by McKenna is an in-depth review of the biochemistry and the role of these proteases in infection.

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Streptococcus pyogenes: disease and molecular pathogenesis 2

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