Novel vancomycin&ndash;peptide conjugate as potent antibacterial agent against vancomycin-resistant <em>Staphylococcus aureus</em>

Abstract

BackgroundIncrease in vancomycin (Van)-resistant bacterial strains including vancomycin-resistant Staphylococcus aureus (VRSA) and lack of new effective antibiotics have become a formidable health problem.Materials and methodsWe designed a new conjugate composed of Van and a peptide Hecate (Hec; Van/Hec), and its potential antimicrobial activity was evaluated.ResultsResults from disk diffusion test, time-kill assay, determination of minimum inhibitory concentration (MIC), microscopy, and comet assay showed strong antimicrobial effects of Van/Hec against wild-type, methicillin-resistant Staphylococcus aureus (MRSA) and VRSA. Microscopy revealed that the exposure to Van/Hec results in disruption of bacterial cell integrity in all tested strains, which was not observed in case of Van or Hec alone.ConclusionOverall, we showed that the preparation of conjugates from antibiotics and biologically active peptides could help us to overcome the limitation of the use of antibiotic in the treatment of infections caused by multidrug-resistant bacteria.

A Novel Ruthenium Based Coordination Compound Against Pathogenic Bacteria

“…The reduction of bacterial cell death by cell wall disruption, cell morphology change, and cell death, which can conclude from optical microscopy ( Figure 7) and fluorescence microscopy images (Figure 8). This result further support that synthesized RU-S4 has high antimicrobial activity [25,36]. Optical microscopy along with fluorescence LIVE/DEAD cell imaging and SEM imaging shows bacterial cells are damaged, deformed, and lysed (Figures 7 and 8).…”

“…The MTT assay reflects metabolic healthy conditions of cells by estimating mitochondrial succinate dehydrogenase. Mitochondrial succinate dehydrogenase reduces MTT and water-insoluble purple color formazan crystal was formed, and the amount of formazan produced is directly proportional to viable cells [25,26]. From the graph, we can conclude that after the application of all desired concentrations of RU-S4 no significant cell mortality rate was found ( Figure 5).…”

“…Antibacterial activity of the RU-S4 compound was studied by turbidimetry technique, the absorbance was measured at 600 nm for 24 h against MRSA (ST239: SCCmecIIIA), VRSA (CCM 1767), S. aureus (NCTC 8511), and hospital sample Staphylococcus epidermidis [19][20][21][22][23][24]. The bacterial viability was calculated as mentioned in our previous work [25]. It was evaluated from the growth curve and viability curve that the ruthenium compound has the most adverse effects on all bacterial species used in this experiment.…”

“…The viability of S. aureus, VRSA (CCM 1767), and MRSA (ST239: SCCmecIIIA) ( Figure 8) and S. epidermidis ( Figure S14) after treatment with RU-S4 was observed by the LIVE/DEAD cell imaging assay [8,25,27]. The bacterial samples treated with RU-S4 showed considerably decreased cell count with green fluorescent, but a significant increase in number of dead cells with red fluorescence, whereas in the case of control bacterial cells, the number of green fluorescent cells were high with red fluorescence (Figure 8 and Figure S14).…”

Characteristic of AMP and the effects of chemical modifications on the modulation of their antimicrobial properties

“…3). Dodatkowo, Van/Hec nie jest toksyczny dla komórek nabłonkowych oraz ludzkich erytrocytów, dzięki czemu postrzegany jest jako innowacyjny antybiotyk w leczeniu zakażeń wywołanych przez oporne szczepy gronkowców [62].…”