February 28, 2018
Brian Geisbrecht to present Biochemistry and Molecular Biophysics Seminar on March 1
Submitted by Biochemistry and Molecular Biophysics
Brian Geisbrecht, professor of biochemistry and molecular biophysics, will present "Evasion of the Complement/Neutrophil Axis by Staphylococcus aureus: A Biochemical Perspective" as part of the Biochemistry and Molecular Biophysics Seminar series at 4 p.m. Thursday, March 1, in 13 Leasure Hall.
The human body relies on neutrophils to provide a sterilizing innate immune response against bacterial pathogens. Although neutrophils circulate inside the blood in a quiescent state, they are rapidly activated in response to a number of biochemical patterns which signify either that potential pathogens are present or that cellular damage has occurred. Activation of neutrophils results in remarkable changes in their morphology, and triggers mobilization and secretion of their cytosolic granules. It is these granules which contain critical components of the neutrophil's antibacterial arsenal. Two of the most abundant components of these granules are the enzyme myeloperoxidase, or MPO, which converts hydrogen peroxide into cytotoxic hypohalous acids, and a series of chymotrypsin-like serine proteases, NSPs, which can directly attack the pathogen cell by cleaving proteins that are either exposed on its surface or secreted into the environment. Together, the combined action of MPO and NSPs form the foundation of neutrophil-mediated innate defense against invading bacteria.
As a consequence of host/pathogen co-evolution, the Gram-positive bacterium Staphylococcus aureus has developed a powerful array of small protein inhibitors that effectively block many of the critical components of the human innate immune response. In this regard, we recently identified three secreted staphylococcal proteins, called Eap, EapH1 and EapH2 — denoted "EAP proteins" — which potently inhibit NSPs, as well as a novel staphylococcal inhibitor of MPO, called SPIN. In this presentation, Geisbrecht will describe recent work in these areas with an emphasis on the unique structural and mechanistic insights we have gained through these studies.