Analysis and Evasion of Pathogen-derived Lysozyme Inhibitors

Project Leader

Karl E. Griswold, Ph.D.
Associate Professor
Thayer School of Engineering at Dartmouth

Co-Investigator

Brent Berwin, Ph.D.
Associate Professor, Microbiology and Immunology
Geisel School of Medicine at Dartmouth

Research in the Griswold laboratory is focused on engineering, development, and analysis of therapeutic proteins, and a substantial effort is directed towards addressing the public health crisis of drug-resistant bacterial pathogens. P. aeruginosa is a common cause of nosocomial infections as well as a dominant factor in chronic infections associated with cystic fibrosis. P. aeruginosa has a larger genome than other common bacterial pathogens, and this fact is thought to be key driver behind the bacterium's propensity to acquire multi-drug resistance and even pan resistance. As a result, there is a need to develop alternative antibacterial therapies for this dangerous opportunistic pathogen. Antibacterial proteins derived from the innate immune system represent interesting leads, and in particular human lysozyme exhibits a broad range of therapeutically relevant characteristics. However, even this powerful antibacterial enzyme can be subverted by bacterial pathogens. P. aeruginosa has been found to express at least two potent lysozyme inhibitory proteins, and early reports suggest that these lysozyme inhibitors may be important pathogenic factors. This project seeks to quantify these proteins' capacity to protect P. aeruginosa from lysozyme in vitro, assess the pathogenic significance of these proteins in vivo, and build a foundation for future molecular engineering studies that will create high performance lysozyme variants able to evade these potent, pathogen-derived inhibitors

This project is collaboration between the Griswold and Berwin research groups. Dr. Griswold has other past and ongoing collaborative studies with COBRE investigators at Dartmouth and the University of Vermont.

Students & Staff

Regina Salvat, Student
Validation and Optimization of Protein Deimmunization Algorithms

Daniel Osipovitch, Student
Engineering Autolysins for Antimicrobial Therapy

Jonathan Guerrette, Student
Design and Development of a Bioresorbable Surgical Sponge

Yongliang Fang, Student
COBRE project, Genetically Engineered Lysozyme as an Anti-Pseudomonal Agent

Kristina Blazanovic, Student
Deimmunizing anti-Staphylococcal Lytic Enzymes

Dr. Hongliang Zhoa, Visiting Scientist
Deimmunizing anti-Staphylococcal Lytic Enzymes

Dr. Chrsitan Ndong, Postdoctoral Fellow
Molecular Targeting of Nanoparticle Cancer Therapies

Dr. Sarah Dostal, Research Associate
High Throughput Screening for Antimicrobial Enzymes

Dr. Wen Li, Research Associate
Molecular Targeting of Nanoparticle Cancer Therapies Therapeutic Protein Deimmunization

Pubmed