Broad-spectrum antibacterial activity by a novel abiogenic peptide mimic

Abstract

The human-mediated use and abuse of classical antibiotics has created a strong selective pressure for the rapid evolution of antibiotic resistance. As resistance levels rise, and the efficacy of classical antibiotics wanes, the intensity of the search for alternative antimicrobials has increased. One class of molecules that has attracted much attention is the antimicrobial peptides (AMPs). They exhibit broad-spectrum activity, they are potent and they are widespread as part of the innate defence system of both vertebrates and invertebrates. However, peptides are complex molecules that suffer from proteolytic degradation. The ability to capture the essential properties of antimicrobial peptides in simple easy-to-prepare molecules that are abiotic in origin and non-proteolytic offers many advantages. Mechanistic and structural knowledge of existing AMPs was used to design a novel compound that mimics the biochemical activity of an AMP. This report describes the development and in vitro characterization of a small peptide mimic that exhibited quick-acting and selective antibacterial activity against a broad range of bacteria, including numerous clinically relevant strains, at low MIC values.

Bactericidal Effects and Mechanism of Action of Olanexidine Gluconate, a New Antiseptic

“…Once inside the membrane, the probe aggregates and self-quenches. With the addition of a membrane-disrupting agent, such as antiseptics, the probe is released, and an increase in fluorescence can be monitored over time (12,(21)(22)(23). In this experiment, S. aureus (strain ATCC 29213) cultivated at 35°C during log-phase growth was harvested by centrifuge, washed with 5 mM HEPES-KOH buffer (pH 7.2) containing 20 mM glucose, and then diluted to about 2 ϫ 10 7 CFU/ml in 5 mM HEPES-KOH buffer containing 20 mM glucose and 100 mM KCl.…”

Impairment of IFN-Gamma Response to Synthetic Peptides of Mycobacterium tuberculosis in a 7-Day Whole Blood Assay

“…Because peptides are degraded more easily by proteases present in whole blood than recombinant proteins [39], [40], we hypothesized that insufficient peptide concentrations were present after 7 days of culture to continue stimulating T cells. In order to detect possible peptide degradation, we compared the SELDI-TOF mass spectrometry profiles of ESAT-6 and CFP-10 peptide pools and recombinant proteins in the supernatants of whole blood assays from 2 donors collected at Day 0 and after 7 days of incubation.…”

Evaluation of cell membrane integrity as a potential antimicrobial target for plant products

“…This dye is known to distribute between bacterial cells and the surrounding medium, depending on the membrane potential gradient [4]. Once inside the membrane, the dye aggregates and self-quenches.…”

“…The method of Nusslein et al [4] was used to investigate the cytoplasmic membrane permeabilizing properties of the extracts of C. citrinus and V. adoensis against bacterial cell membranes using disC3-5. Bacterial cells were grown to mid-exponential phase and collected by centrifugation.…”

“…As resistance levels rise, the efficacy of classical antibiotics wanes. Bacterial drug resistance is emerging as one of the most significant challenges to human health [4]. Multi-drug resistant microbial infections caused by Gram positive bacteria such as Staphylococcus aureus and Enterococcus faecalis represent an exponentially growing problem affecting communities worldwide [5].…”