Human microbiome derived synthetic antimicrobial peptides with activity against Gram-negative, Gram-positive, and antibiotic resistant bacteria.

Walaa K Mousa, Ashif Y Shaikh, Rose Ghemrawi, Mohammed Aldulaimi, Aya Al Ali, Nour Sammani, Mostafa Khair, Mohamed I Helal, Farah Al-Marzooq, Emilia Oueis
Author Information
  1. Walaa K Mousa: College of Pharmacy, Al Ain University PO BOX 64141 Abu Dhabi United Arab Emirates walaa.mousa@aau.ac.ae.
  2. Ashif Y Shaikh: Department of chemistry, Khalifa University of Science and Technology PO BOX 127788 Abu Dhabi United Arab Emirates emilia.oueis@ku.ac.ae.
  3. Rose Ghemrawi: College of Pharmacy, Al Ain University PO BOX 64141 Abu Dhabi United Arab Emirates walaa.mousa@aau.ac.ae.
  4. Mohammed Aldulaimi: Department of chemistry, Khalifa University of Science and Technology PO BOX 127788 Abu Dhabi United Arab Emirates emilia.oueis@ku.ac.ae. ORCID
  5. Aya Al Ali: College of Pharmacy, Al Ain University PO BOX 64141 Abu Dhabi United Arab Emirates walaa.mousa@aau.ac.ae.
  6. Nour Sammani: College of Pharmacy, Al Ain University PO BOX 64141 Abu Dhabi United Arab Emirates walaa.mousa@aau.ac.ae.
  7. Mostafa Khair: Core Technology Platforms, New York University Abu Dhabi PO BOX 127788 United Arab Emirates.
  8. Mohamed I Helal: Electron Microscopy Core Labs, Khalifa University of Science and Technology PO BOX 127788 Abu Dhabi United Arab Emirates.
  9. Farah Al-Marzooq: Department of Medical Microbiology and Immunology, College of Medicine and Health Sciences, UAE University P.O. Box 15551 Al Ain United Arab Emirates.
  10. Emilia Oueis: Department of chemistry, Khalifa University of Science and Technology PO BOX 127788 Abu Dhabi United Arab Emirates emilia.oueis@ku.ac.ae. ORCID

Abstract

The prevalence of antibacterial resistance has become one of the major health threats of modern times, requiring the development of novel antibacterials. Antimicrobial peptides are a promising source of antibiotic candidates, mostly requiring further optimization to enhance druggability. In this study, a series of new antimicrobial peptides derived from lactomodulin, a human microbiome natural peptide, was designed, synthesized, and biologically evaluated. Within the most active region of the parent peptide, linear peptide with the sequence LSKISGGIGPLVIPV-NH and its cyclic derivatives and showed strong antibacterial activity against Gram-positive bacteria, including resistant strains, and Gram-negative bacteria. The peptides were found to have a rapid onset of bactericidal activity and transmission electron microscopy clearly shows the disintegration of the cell membrane, suggesting a membrane-targeting mode of action.

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Word Cloud

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