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Opa Proteins

Neisseria gonorrhoeae and Neisseria meningitides are pathogenic, obligate, gram-negative bacteria responsible for a variety of diseases including meningococcal meningitis and gonorrhea. Subsequent to pili binding, opacity associated (Opa) proteins bind to host plasma membrane receptors and signal the loss of the pili and host actin reorganization, which facilitates endocytosis into the host cytoplasm. Different Opa proteins bind to various host receptors and are classified into two classes. The larger class, OpaCEA, bind to carcinoembryonic antigen-like cellular adhesion molecules (CEACAMs), and the smaller class, OpaHS, bind to  heparansulfate proteoglycan receptors (HSPGs).

The Columbus laboratory is determining the structure of Opa proteins and mapping their interactions to host receptors. We are also exploring how the bacterial membrane, including lipopolysaccharide (LOS), impacts receptor binding and cellular uptake.
Neisseria gonorrhoeae co-opts C4b-binding protein to enhance complement-independent survival from neutrophils.

Werner LM, Alcott A, Mohlin F, Ray JC, Belcher Dufrisne M, Smirnov A, Columbus L, Blom AM, Criss AK.

Variable Expression of Opa Proteins by Neisseria gonorrhoeae Influences Bacterial Association and Phagocytic Killing by Human Neutrophils.
Imaging flow cytometry analysis of CEACAM binding to Opa-expressing Neisseria gonorrhoeae.

Werner LM*, Palmer A*, Smirnov A, Belcher-Dufrisne M, Columbus L, Criss AK

Cytometry: Part A. 97:1081-1089. (2020). PMC8062897

CEACAM targeted liposome delivery

Kuhn J, Smirnov A, Criss AK, Columbus L

Molecular Pharmaceutics. 16:2354 - 2363 (2019). PMC6740330

Refinement of highly flexible protein structures using simulation-guided spectroscopy.

Hays JM, Kieber MK, Li JZ, Han JI, Columbus L, Kasson PM.

Angnewandte Chemistry. 57:17110 – 17114 (2018). PMC6424112  

Neisserial Opa protein – CEACAM interactions: competition for receptors as a means for bacterial invasion and pathogenesis.

Martin J, Ball L, Solomom T, Criss A, Columbus L.

Biochemistry 55: 4286 – 4294 (2016). PMC4980159

Opa+ Neisseria gonorrhoeae has reduced survival in human neutrophils via Src family kinase-mediated bacterial trafficking into mature phagolysosomes.

Johnson MB, Ball LM, Daily KP, Martin JN, Columbus L, and Criss AK.

Cellular Microbiology. 17:648 – 665 (2015). PMC4402142

The Structure of the Neisserial outer membrane protein Opa60: Loop flexibility essential to receptor recognition and bacterial engulfment.

Fox DA, Larsson P, Lo RH, Kroncke BM, Kasson P, Columbus L.

Journal of the American Chemical Society. 136:9938 – 9946 (2014). PMC4105060

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