Folding Behaviour and Antibacterial Activity of Ionic Complementary Peptide EAK-16
Abdul Majid
*
Department of Biochemistry, Shah Abdul Latif University Khairpur, Post Code: 66020, Sindh, Pakistan.
Farah Naz
Department of Biochemistry, Shah Abdul Latif University Khairpur, Post Code: 66020, Sindh, Pakistan.
Hatim Ali Jamro
Department of Biochemistry, Shah Abdul Latif University Khairpur, Post Code: 66020, Sindh, Pakistan.
Sham Lal
Institute of Microbiology, Shah Abdul Latif University, Khairpur, Post Code: 66020, Sindh, Pakistan.
Inayatullah Soomro
Department of Mathematics, Shah Abdul Latif University, Khairpur, Post Code: 66020, Sindh, Pakistan.
Sanaullah Abbasi
Department of Biochemistry, Shah Abdul Latif University Khairpur, Post Code: 66020, Sindh, Pakistan.
Safdar Ali Ujjan
Department of Zoology, Shah Abdul Latif University, Khairpur, Post Code: 66020, Sindh, Pakistan.
*Author to whom correspondence should be addressed.
Abstract
Aim: A major challenge in the development of new antibiotics is the biocompatibility within biological environment. Ionic complementary peptide (EAK-16) from amyloid protein, have the ability to adopt secondary structure conformation at membrane interfaces. This study aimed to investigate the effect of membrane on EAK-16 peptide folding and their antibacterial applications.
Methodology: We studied secondary structural conformation of EAK-16 using circular dichroism (CD) spectroscopy in an aqueous environment and at membrane bilayers interfaces. Initially, the antibacterial efficacy was investigated against both Gram-positive and Gram-negative bacteria. Membrane mimicking models were synthesised with dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylserine (DMPS) lipid vesicles using calcein leakage assay.
Results: EAK-16 showed transition in secondary structural conformation. In aqueous environment, it was predominantly β-sheets and at membrane interfaces, it was mainly α-helical. EAK-16 peptide was highly active against bacteria (at minimum concentration applied) and membrane leakage was found to be > 60%. This effect was confirmed with both anionic lipids (DMPS) and neutral lipids (DMPC). The helical transition of EAK-16 could be a major factor to disrupt the membrane and bacterial death
Conclusion: The secondary structural conformation and calcein leakage data suggest that EAK-16 has potential to kill bacteria by adopting helical tilted conformation and membrane perturbation via lysis. This study revealed structure-function relationship of peptide and lipid bilayers to further investigate the mode of pore formation and mode of action of EAK-16 in membrane perturbation and antibacterial efficacy.
Keywords: Antibacterial peptide, ionic complementary peptide, peptide lipid interactions, secondary structure conformation, membrane leakage