Biophysical Studies of the Effects of Antimicrobial and Cell Penetrating Peptides on Vesicles Mimicking Bacterial and Mammalian Membranes
Drug-resistant bacteria remains a challenge in infectious diseases, and the need for the development of new antimicrobial agents cannot be overstated. Antimicrobial peptides (AMPs) from innate immunity of animals are among the most interesting candidates for this role, due to their efficacy against pathogens and their likelihood to not induce drug resistance. However, their physical properties present challenges in the creation of biologically stable agents and in balancing antimicrobial efficacy against host cell membrane toxicity, and their killing mechanism is still open to debate. On the other hand, the prevalence of neurodegenerative diseases in USA and high-income countries is devastating the healthcare system. There is a need for drug delivery systems. Cell penetrating peptides (CPPs) are considered as potential drug delivery vectors, because they are able to cross the cell membrane either by themselves or together with a molecule cargo. Nevertheless, their entry mechanism into cell is still unclear.These two families of peptides are a possible answer to the treatment of drug-resistant bacteria and the exploration of drug delivery systems. The objective of this project is to carry out a detailed analysis of the interaction between selected AMPs and CPPs and vesicles mimicking bacterial and mammalian membranes using biophysical techniques. AMPs composed of RW units seem to be very powerful against pathogens. We hypothesize that increasing the net positive charge and the hydrophobic moment will improve their affinity for bacterial membranes and moderate their toxicity. We also hypothesize that the use of advanced model membranes will provide new insights into the mechanism of entry of CPPs and AMPs into the cells. We used spectroscopic techniques as well as biological assays measuring the minimum inhibitory concentration (MIC) values for AMPs. Some AMPs have shown ultralow MIC values against some WHO top priority pathogens. Overall, this project has presented (1) a sequence template composed of (RW)n units that can be used to design potential alternatives for conventional antimicrobial agents and (2) the threshold concentrations that trigger direct translocation of the CPPs Pep-1 and penetratin. The techniques employed here can be used in a complementary way to study peptide-lipid interactions.
"Biophysical Studies of the Effects of Antimicrobial and Cell Penetrating Peptides on Vesicles Mimicking Bacterial and Mammalian Membranes"
ETD Collection for Tennessee State University.