In Vitro Synergistic Activities of the Hybrid Antimicrobial Peptide MelitAP-27 in Combination with Conventional Antibiotics Against Planktonic and Biofilm Forming Bacteria

Abstract

The extensive use of antibiotics for the treatment of human infections during the last few decades has led to a dramatic increase in the emergence of multidrug-resistant bacteria (MDRB) among various bacterial strains. Global research is currently focused on finding novel alternative agents with different mechanisms of action rather than the use of conventional antibiotics to counteract the threat of bacterial and biofilm infections. Antimicrobial peptides represent promising alternative agents for conventional antibiotics as these molecules display a broad spectrum of activity against several microorganisms. Recently, we have designed a novel hybrid antimicrobial peptide named MelitAP-27. This peptide has been found to display potent broad spectrum and selective in vitro antimicrobial activities against a wide range of Gram-positive and Gramnegative bacteria. In the present study, the in vitro antimicrobial and antibiofilm activities of the peptide alone and in combination with five different types of antibiotics were assessed against wild-type and resistant Gram-positive and Gram-negative bacterial strains. Our results showed that most of the combination groups displayed a synergistic mode of action against planktonic and biofilm forming bacteria which resulted in decreasing the effective MIC values for MelitAP-27 to the nanomolar concentrations. These effective concentrations were associated with negligible toxicities on mammalian cells. The results of our study indicate that combinations of MelitAP-27 with conventional antibiotics may be pursued as a potential novel treatment strategy against MDRB and biofilm forming bacteria.

<p>The evaluation of the synergistic antimicrobial and antibiofilm activity of AamAP1-Lysine with conventional antibiotics against representative resistant strains of both Gram-positive and Gram-negative bacteria</p>

“…For the planktonic Gram-positive bacteria, three peptide-antibiotic combinations proved to be highly synergistic and these include levofloxacin, rifampicin and erythromycin. The levofloxacin combination proved to be the most potent with a FIC index of 0.103 against the resistant strain of S. aureus (ATCC 33591) and in accordance synergistic studies performed previously 29–31. For Gram-negative bacteria, only two combinations displayed a synergistic activity, and these include levofloxacin and chloramphenicol.…”

Synergistic Antibacterial Activity of Designed Trp-Containing Antibacterial Peptides in Combination With Antibiotics Against Multidrug-Resistant Staphylococcus epidermidis

“…However, combination of these antibiotics with the Trp-containing peptides proved to be highly successful in inhibiting biofilm formation. Similarly, Almaaytah et al demonstrated that the combinations of ampicillin and erythromycin with MelitAP-27, a novel hybrid antimicrobial peptide, displayed highly significant synergistic activity against biofilm formation by S. aureus (33591) and Pseudomonas aeruginosa (BAA2114), respectively (Almaaytah et al, 2016). FLIP7 is an AMP complex of the blowfly Calliphora vicina containing a combination of defensins, cecropins, diptericins and proline-rich peptides and has also demonstrated high synergistic antibiofilm activity with ampicillin and erythromycin against S. aureus and Escherichia coli (Chernysh et al, 2018).…”

“…Over the last few decades, a growing number of multidrug-resistant bacterial species have dramatically increased because of the widespread use of antibiotics, which has become a major problem for health care centers worldwide. Although the development of novel antibiotics with different mechanisms of action has been carried out, processes of novel drug discovery and development usually span 10–17 years, and the success rate is lower than 10% (Ashburn and Thor, 2004; Spellberg et al, 2013; Almaaytah et al, 2016). Furthermore, new resistant strains will inevitably emergence again as the widespread use and misuse of novel drugs with a single target of action.…”

An Atlas of Anionic Antimicrobial Peptides from Amphibians

“…For example, XLAsp-P1 appeared to kill bacteria using a toroidal pore type mechanism, and the action of XLAsp-P2 shows hallmark characteristics of the SHM model of membrane interaction. This latter peptide also showed the ability to potentiate the action of conventional antibiotics against MDR pathogens, and the potential advantages of this form of combination therapy are increasingly being recognised and are viewed as a major, potential strategy for combating microbial pathogens with MDR [137][138]. For example, combination treatment can potentially reduce the required dosage of individual drugs, thereby diminishing side effects, as well as, not only eliminating resistant strains, but also delaying the emergence of drug resistance [139][140].…”