Antje Pokorny Almeida



Function and Specificity of Membrane-Active Peptides

Essentially all living beings have evolved a primary defense mechanism directed at invading or competing organisms. The molecules that constitute these defensive systems are often simple peptides or small proteins that are often specific for a particular target organism. For instance, human saliva contains a class of antimicrobial peptides called defensins that help prevent infestation of the oral cavity by yeasts and bacteria. Interestingly, most antimicrobial and cytolytic peptides bind to their targets without the involvement of specific cell surface receptors. Nevertheless, all of the peptides studied have to interact with the plasma membrane of the target organism to either enter the cell or somehow disrupt membrane integrity. In collaboration with the lab of Paulo Almeida, we have been studying the mechanisms of linear, α-helical peptides and the role of both peptide structure and lipid composition of the target membrane in the process.

More recently, we have been looking more closely at lipopetides, of which the antibiotic daptomycin is a representative example. Here, we are interested in the role of membrane-bound calcium ions and how binding of calcium ions to lipopetides promotes lipid clustering.

Bacterial Membranes

The purpose of this project is to understand how lipids typically found in pathogenic bacteria like Staphylococcus aureus influence activity and target specificity of antimicrobial peptides. Why are we interested in S. aureus? Because methicillin-resistant S. aureus strains (MRSA) are a significant health concern in hospitals world-wide. These highly pathogenic strains have become not only resistant to conventional antibiotics but also to antimicrobial peptides secreted by platelets and neutrophils - and acquired bacterial resistance to antimicrobial peptides has been linked to altered lipid profiles in the bacterial cell membrane.

Bacteria often incorporate lipids not found in eukaryotic cells into their cell membranes. S. aureus, for instance, uses iso- and anteiso-branched lipid acyl chains to maintain cell membrane fluidity. Very little is known about these lipids, their structure, how they are organized in the cell membrane, and how they affect peptide-membrane interactions. We collaborate with the lab of Brian Wilkinson at Illinois State University on this project.

Other Things I Think About

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Recent Publications

Kelly M. Hines, Gloria Alvarado, Craig Gatto, Antje Pokorny, Brian J. Wilkinson, and Libin Xu. (2020). Lipidomic and Ultrastructural Characterization of the Cell Envelope of Staphylococcus aureus Grown in the Presence of Human Serum. mSphere 5(3):e00339-2.[DOI: 10.1128/mSphere.00339-20]

Pokorny, A., Tala O. Khatib, and Heather Stevenson. (2018). An Exact Model of Daptomycin Binding to Lipid Bilayers. J. Phys. Chem. B 122:9137-9146.[DOI: 10.1021/acs.jpcb.8b0750]

Kreutzberger, M.A., Pokorny, A., and Almeida, P. (2017). Daptomycin-Phosphatidylglycerol Domains in Lipid Membranes., Langmuir. 33:13669-13679.[DOI: 10.1021/acs.langmuir.7b01841]

Singleton, E.M.*, McLellan, W.A., Koopman, H.N., Pokorny, A. Scharf, F.S. and Pabst, D.A. (2017). Lipid composition and thermal properties of the blubber of Gervais’ beaked whale (Mesoplodon europaeus) across ontogeny. Marine Mammal Science. DOI: 10.1111/mms.12389 [DOI:10.1111/mms.12389]

Mitchell, N., Seaton, P., and Pokorny, A. (2016). Branched Phospholipids Render Lipid Vesicles More Susceptible to Membrane-active Peptides. Biochem. et Biphysica Acta 1858: 988–994. [DOI: 10.1016/j.bbamem.2015.10.014]

Cherry, M., Higgins, S., Melroy, H., Lee, H.-S., and Pokorny, A. (2014) Peptides with the same composition, hydrophobicity, and hydrophobic moment bind to phospholipid bilayers with different affinities. J. Phys. Chem. B. 118:12462–12470.[DOI: 10.1016/10.1021/jp507289w]

Cox, E, Michalak, A., Pagentine, S., Seaton, P. and Pokorny, A. (2014). Lysylated phospholipids stabilize models of bacterial lipid bilayers and protect against antimicrobial peptides. Biochem. et Biphys. Acta 1838:2198-2204. [DOI: 10.1016/j.bbamem.2014.04.018]

Kreutzberger, A.J. and Pokorny, A. (2012). On the origin of multiphasic kinetics in peptide binding to phospholipid vesicles. J. Phys. Chem. B. 116:951-957. [DOI: 10.1021/jp209080m]

Almeida, P.F. and Pokorny, A. (2012). Interactions of antimicrobial peptides with lipid bilayers. In Lukas Tamm (Ed.), Comprehensive Biophysics. Elsevier.

Dunkin, C., Pokorny, A., Almeida, P., and Lee, H.-S. (2011). Studies of Transportan 10 (Tp10) Interacting with a POPC Lipid Bilayer. J Phys. Chem. B. 115:1188-1198. [DOI: 10.1021/jp107763b]

Kilelee, E, Pokorny, A, Yeaman, M.R., and Bayer, A,S. (2010). Lysyl-Phosphatidylglycerol Attenuates Membrane Perturbation Rather than Surface Association of the Cationic Antimicrobial Peptide 6W-RP-1 in a Model Membrane System: Implications for Daptomycin Resistance. Antimicrob. Agents Chemother. 54:4476-4479. [DOI: 10.1128/AAC.00191-10]