Synergistic Effects and Antibiofilm Properties of Chimeric Peptides against Multidrug-Resistant Acinetobacter baumannii Strains

Abstract

fThe increasing prevalence of drug-resistant pathogens highlights the need to identify novel antibiotics. Here we investigated the efficacies of four new antimicrobial peptides (AMPs) for potential drug development. The antibacterial activities, synergistic effects, and antibiofilm properties of the four chimeric AMPs were tested against Acinetobacter baumannii, an emerging Gramnegative, nosocomial, drug-resistant pathogen. Nineteen A. baumannii strains resistant to ampicillin, cefotaxime, ciprofloxacin, tobramycin, and erythromycin were isolated at a hospital from patients with cholelithiasis. All four peptides exhibited significant antibacterial effects (MIC ‫؍‬ 3.12 to 12.5 M) against all 19 strains, whereas five commercial antibiotics showed little or no activity against the same pathogens. An exception was polymyxin, which was effective against all of the strains tested. Each of the peptides showed synergy against one or more strains when administered in combination with cefotaxime, ciprofloxacin, or erythromycin. The peptides also exhibited an ability to prevent biofilm formation, which was not seen with cefotaxime, ciprofloxacin, or erythromycin, though polymyxin also inhibited biofilm formation. Indeed, when administered in combination with ciprofloxacin, the AMP HPMA exerted a potent synergistic effect against A. baumannii biofilm formation. Collectively, our findings indicate that the AMPs tested have no cytotoxicity but possess potent antibacterial and antibiofilm activities and may act synergistically with commercial antibiotics.

Surface-attached cells, biofilms and biocide susceptibility: implications for hospital cleaning and disinfection

“…82e84 For example, a range of antimicrobial peptides tested against multi-drug-resistant A. baumannii demonstrated direct antimicrobial activity, and enhanced the activity of a range of other antimicrobial agents. 82 However, the addition of enzymes, quorum-sensing inhibitors or antimicrobial peptides into a cleaning or disinfection solution would result in chemical residues on surfaces with associated health and safety implications, so are not recommended without further study. Another approach is the inclusion of bacteriophages, which have been found to disrupt biofilms.…”

Synthetic antibiofilm peptides

“…These include largely unexplored toxicities, long amino acid sequences that increase production costs, degradation by host proteases, and limited understanding about the structure-function relationships of these peptides [6]. Researchers have attempted to solve some of these limitations by performing physicochemical modifications to peptides, such as deletion and/or substitution of amino acid residues, cyclization, design of retro-inverso peptides and the use of D-enantiomer amino acids [18], sequence truncations [19] and construction of hybrids [20], or by computational methods [5–7, 21, 22]. Examples of synthetic peptides with antibiofilm properties that have been described to date are outlined in Table 1.…”

Design and membrane-disruption mechanism of charge-enriched AMPs exhibiting cell selectivity, high-salt resistance, and anti-biofilm properties

“…The methanol was then discarded, and the biofilm attached to the well was stained with 0.1 % (wt/vol) crystal violet solution for 1 h, after which the excess stain was repeatedly rinsed away with distilled water. Finally, 200 µl of 100 % ethanol was added to each well, and activity was measured based on the OD 595 using a Versa-Max microplate enzyme-linked immunosorbent assay (ELISA) reader (Molecular Devices, Sunnyvale, CA, USA) (Gopal et al 2014). …”