The discovery of antibiotics is one of the most important ones in the history of humankind.
For eighty years the life expectancy and the standards of living of humans greatly improved largely thanks to antibiotics.
But the age of antibiotics is "now well and truly over". New and alternative strategies must be explored as antibiotic therapies become obsolete because of bacterial resistance.
We model, design, construct and test synthetic biological systems. We are focusing on antibiotic molecules, such as antimicrobial peptides, and on "smart" delivery vehicles, such as recombinant lactic acid bacteria.
In this picture Lactococcus lactis (white) drawn in the shape of the Asclepius’ rod (a common symbol of health and medicine) on a field of pathogenic Enterococcus faecalis (blue). L. lactis has been engineered to produce antimicrobial peptides that result in a zone of pathogen inhibition surrounding L. lactis. Bacteria were plated on brain heart infusion agar containing X-gal to result in coloration of β-galactosidase-producing E. faecalis. Photograph taken by Kathryn Geldart with editing by Jeffrey Ting, University of Minnesota.
We recently published a manuscrpit in Applied and Environmental Microbiology discussing results of an enhanced Lacococcus lactis that targets antibiotic-resistant enterococcal strains.
For the manuscript go to doi.org/10.1128/AEM.00227-15
We recently published a manuscript in ACS Synthetic Biology with proof-of-concept results of antibiotic cellbots. For a summary visit our Research pages.
For the manuscript go to http://pubs.acs.org/doi/abs/10.1021/sb500090b
In a Proceedings of the National Academy of Sciences of the USA paper entitled, “A closure scheme for chemical master equations”, Smadbeck and Kaznessis offer a solution to a mathematical problem that remained unsolved for over seventy years. The Minnesota team developed a numerical closure scheme for the equation that governs random molecular events in biological systems. Randomness is a defining feature of biomolecular systems, determining all too frequently the fate of a living organism. The most complete model of randomly evolving molecular populations is one based on the master probability equation. The “master” in the name reflects the all-encompassing nature of an equation that purports to govern all possible outcomes for all time. Because of its ambitious character, the master equation remained unsolved for all but the simplest of molecular interaction networks. Now, with the first complete solution of chemical master equations, a wide range of experimental observations of biomolecular interactions may be mathematically conceptualized.
Professor Kaznessis' textbook "Statistical Thermodynamics and Stochastic Kinetics: An Introduction for Engineers" is published by Cambridge University Press www.cambridge.org/9780521765619
Recent Research Highlights:
Juan Borrero and Katherine Volzing engineered lactic acid bacteria to produce antimicrobial peptides that specifically target E. coli or salmonella. Click here for the article.
Recent Research Highlights:
How do antimicrobial peptides work? Dr. Dan Bolintineanu, Dr. Allison Langham and Professor Yiannis Kaznessis, Department of Chemical Engineering and Materials Science, simulated the pore that is formed by protegrin-1, a potent antimicrobial peptide, in the lipid bilayer membrane of bacteria. Molecular dynamics simulations coupled with Poisson-Nernst-Planck electrodiffusion equations show exactly how a protegrin pore allows ions and other cell contents to leak out of the bacterion, causing its death. In the picture, the cross sectional view of a protegrin-1 pore (in green) in a lipid bilayer is shown (lipid chains in grey and lipid heads in red; water is cyan). The movement of ions through the pore was visualized using molecular dynamics simulations (in yellow, a chloride ion is shown as it moves through the pore). This information helps to elucidate the mechanism of action by which this antimicrobial peptide kills bacteria and rationalizes engineering of novel, potent antibiotic molecules. The top view of the full system is shown in the insert. With a clear picture of the physical interactions that underlie biological function we set out to engineer new antibiotics.For more information visit our publications webpage and consult the following:
Langham A., Sayyed-Ahmad A, Kaznessis YN, “On the nature of antimicrobial activity: a model for Protegrin-1 pores”, JACS, 2008, 130(13): 4338-4346.
Bolintineanu D, Hazrati E, Davis HT, Lehrer RI, Kaznessis YN. “Antimicrobial mechanism of pore-forming protegrin peptides: 100 pores to kill E. coli.” Peptides. 2010.
D. Bolintineanu, HT. Davis, YN. Kaznessis, “Poisson-Nernst-Planck models of nonequilibrium ion electrodiffusion through a protegrin transmembrane pore”, PLoS Computational Biology, 2009.