<p>Design and characterization of a new hybrid peptide from LL-37 and BMAP-27</p>

Abstract

Background and purpose: The world is heading to a post-antibiotic era where the treatment of bacterial infections will not be possible even with well-known last-line antibiotics. Unfortunately, the emergence of multidrug resistant bacterial strains is uncontrollable, and the humanity will face a life-threatening fate unless new antimicrobial agents with new bacterial target sites are promptly developed. Herein, we design a hybrid antimicrobial peptide (B1) from helical parts taken from the parent peptides: LL-37 and BMAP-27. The purpose of this design is to improve the potency and enhance the toxicity profile of the parent peptides. Methods: Rational design was used to hybridize two antimicrobial peptides, in which two helical parts from the bovine analog BMAP-27, and the human cathelicidin LL-37 were used to generate a novel peptide (B1). The physicochemical properties were checked using in silico methods. The antimicrobial activities were tested against nine control and resistant strains of Gram-positive and Gram-negative bacteria. On the other hand, the antibiofilm activities were tested against four resistant strains. The cytotoxicity on mammalian cells was tested using HEK293, and the hemolysis activity was also investigated on human blood. Finally, synergistic studies were performed with four conventional antibiotics against four resistant strains of Gram-positive and Gram-negative bacteria. Results: The new peptide B1 exhibited broad-spectrum activities against all tested strains. The concentration against planktonic cells ranged between 10 and 20 µM. However, 40–60 µM were needed to eradicate the biofilms. B1 showed reduced toxicity toward mammalian cells with minimal hemolysis risk. On the other hand, the synergistic studies showed improved activities for the combined conventional antibiotics with a huge reduction in their minimum inhibitory concentration values. The concentrations of B1 peptide combined with the tested antibiotics were also decreased markedly down to 0.5 µM in some cases. Conclusion: B1 is a hybrid peptide from two cathelicidin peptides. It showed an improved activity compared to parent peptides. The hybridization was successful in this study. It generated a new potent broad-spectrum antimicrobial. The toxicity profile was improved, and the synergism with the convention antibiotics showed promising results.

A Bifunctional Peptide Conjugate That Controls Infections of Erwinia amylovora in Pear Plants

“…Conjugation of two peptides to obtain sequences with a better biological profile is a widely used strategy. This approach has led to the design of interesting hybrid peptides with significant antimicrobial activity derived from cecropin A, melittin, lactoferricins, thanatin, cathelicidin, and LL-37, among others [ 30 , 31 , 32 , 33 , 34 , 37 , 51 , 52 ]. Within this field, we described peptide conjugates containing the antimicrobial peptide BP100 and fragments of cecropin A, melittin, and magainin [ 13 ].…”

“…The conjugation of two different peptides constitutes an efficient approach to obtain novel compounds with improved antimicrobial activity compared to the individual sequences [ 27 , 28 , 29 ]. In fact, the conjugation of sequences with antimicrobial activity has been extensively reported [ 30 , 31 , 32 , 33 , 34 , 35 ]. In this context, we conjugated the antimicrobial peptide BP100 with fragments of natural antimicrobial peptides to obtain peptide conjugates with improved biological activity against plant pathogens than their corresponding monomers [ 13 ].…”

Metformin as a Potential Adjuvant Antimicrobial Agent Against Multidrug Resistant Bacteria

“…The reaction was classified as synergetic if the FIC ≤0.5, additive if greater than 0.5 or lower/equal than 1, indifferent if greater than 1 but less than 2 and antagonistic if greater or equal to 2. 32 …”

“…The combinations were interpreted, based on EUCAST as synergistic (FIC ≤0.5), additive 0.5< FIC index ≤1, indifferent 1< FIC <2, or antagonistic (FIC≥2). [31][32][33][34] As illustrated in Table 1, the combinations of metformin with the tested antimicrobial agents, against MRSA, were all synergistic, with the exception of rifampicin which was additive. Combining metformin with doxycycline resulted in the highest reduction in the antibiotic MIC with approximately 93% reduction in doxycycline MIC.…”

“…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).…”