The Ultrashort Peptide OW: A New Antibiotic Adjuvant

Abstract

Background: The over use of current antibiotics and low discovery rate of the new ones are leading to rapid development of multidrug-resistant pathogens worldwide. Antimicrobial peptides have shown promising results against multidrug-resistant bacteria. Objective: To investigate the antimicrobial activity of a new ultrashort hexapeptide (OW). Methods: The OW hexapeptide was designed and tested against different strains of bacteria with different levels of sensitivity. Bacterial susceptibility assays were performed according to the guidelines of the Clinical and Laboratory Institute (CLSI). The synergistic studies were then conducted using the Checkerboard assay. This was followed by checking the hemolytic effect of the hexapeptide against human blood cells and Human Embryonic Kidney cell line (HEK293). Finally, the antibiofilm activities of the hexapeptide were studied using the Biofilm Calgary method. Results: Synergistic assays showed that OW has synergistic effects with antibiotics of different mechanisms of action. It showed an outstanding synergism with Rifampicin against methicillin resistant Staphylococcus aureus; ΣFIC value was 0.37, and the MIC value of Rifampicin was decreased by 85%. OW peptide also displayed an excellent synergism with Ampicillin against multidrug-resistant Pseudomonas aeruginosa, with ΣFIC value of less than 0.38 and a reduction of more than 96% in the MIC value of Ampicillin. Conclusion: This study introduced a new ultrashort peptide (OW) with promising antimicrobial potential in the management of drug-resistant infectious diseases as a single agent or in combination with commonly used antibiotics. Further studies are needed to investigate the exact mechanism of action of these peptides.

Dual-Mechanism Glycolipidpeptide with High Antimicrobial Activity, Immunomodulatory Activity, and Potential Application for Combined Antibacterial Therapy

“…θ M is the mean residue ellipticity (deg•cm 2 •dmol −1 ); θ obs is the observed ellipticity after correction by the buffer at a given wavelength (mdeg); c is the peptide concentration (mM); l is the path length (mm); and n is the amino acid number of the peptide.…”

“…The abuse of antibiotics has led to the increasing resistance of many bacteria strains, resulting in a series of superbugs that pose a serious threat to human health. , Therefore, it is urgent to develop effective antibacterial drugs. Antimicrobial peptides (AMPs), as the basic components of the innate immune response in multicellular eukaryotes, have attracted considerable attention as potential candidates against drug-resistant bacteria. , …”

“…The hydrophobicity of AMPs determines the extent to which AMPs can enter the phospholipid bilayer and is one of the necessary conditions for membrane penetration . The hydrophobic tryptophan (Trp, W) can generate negatively charged electron clouds due to the strong quadrupole moment of the π-electron system of aromatic residues, and these electron clouds can interact with cationic molecules (such as choline groups) in the bacterial lipid bilayer, causing a prolonged association with the bacterial lipid membrane. ,, The isoleucine (Ile, I) and aromatic phenylalanine (Phe, F) have hydrophobic interactions with phospholipids that can lead to biological activity. The hydrophobic leucine (Leu, L) and alanine (Ala, A) tend to form α-helical structures.…”

Metformin as a Potential Adjuvant Antimicrobial Agent Against Multidrug Resistant Bacteria

“…The procedure was performed as mentioned in previous studies. 5,32 Using 96-well microplates, 25 µL of metformin and 25 µL of one of the mentioned antibiotics were added to 50 µL of 5×10 5 CFU/mL of each bacterial strain suspension on each well. The microplates were then incubated for 24 h at 37° C. The MICs were then measured at 600 nm using an ELISA microplate reader (EpochTM, BioTeck, Winooski, VT, USA).…”

“… 3 Around 700,000 people die yearly due to infections caused by multidrug resistant (MDR) Gram-positive and Gram-negative bacteria, and this number is expected to further increase and reach up to 10 million deaths by 2050. 4 , 5 The negative impact of infections caused by MDR is extended to impact not only in the health field, but also the economic field due to longer hospitalization and greater costs of longer care when compared with infections caused by antimicrobial susceptible bacteria. 6 The number of antimicrobial medications discovered within the last two decades is much lower compared with previous discoveries.…”