Novel antibiotic treatments are in increasing demand to tackle life-threatening infections from bacterial pathogens. In this study, we report the use of a potent battacin lipopeptide as an antimicrobial gel to inhibit planktonic and mature biofilms of and . The antimicrobial gels were made by covalently linking the -terminal cysteine containing lipopeptide (GZ3.163) onto the polyethylene glycol polymer matrix and initiating gelation using thiol-ene click chemistry. The gels were prepared both in methanol and in water and were characterised using rheology, Fourier transform infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM). Antibacterial and antibiofilm analyses revealed that the gels prepared in methanol have better antibacterial and antibiofilm activity. Additionally, a minimum peptide content of 0.5 wt% (relative to polymer content) is required to successfully inhibit the planktonic bacterial growth and disperse mature biofilms of and . The antibacterial activity of these lipopeptide gels is mediated by a contact kill mechanism of action. The gels are non-haemolytic against mouse red blood cells and are non-cytotoxic against human dermal fibroblasts. Findings from this study show that battacin lipopeptide gels have the potential to be developed as novel topical antibacterial agents to combat skin infections, particularly caused by .
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http://dx.doi.org/10.3390/molecules25245945 | DOI Listing |
Bioorg Chem
September 2024
School of Chemical Sciences and The Centre for Green Chemical Science, University of Auckland, Auckland 1142, New Zealand; The MacDiarmid Institute for Advanced Materials and Nanotechnology, Wellington 6012, New Zealand. Electronic address:
Bioorg Med Chem Lett
November 2023
School of Chemical Sciences, University of Auckland, Auckland, New Zealand; Macdiarmid Institute for Advanced Materials and Nanotechnology, Wellington 6012, New Zealand. Electronic address:
Octapeptin B5 peptides containing a novel fatty acids have been found to have enhanced antibacterial activity against Staphylococcus aureus and also have an excellent safety profile. Cyclic lipopeptides such as the polymyxins and battacin are potent antibacterial agents. It has been shown that truncated, non-linear, versions of these agents (e.
View Article and Find Full Text PDFChem Sci
May 2020
School of Biological Sciences, University of Auckland 3A Symonds Street Auckland 1010 New Zealand.
We herein report the synthesis and biological and computational evaluation of 12 linear analogues of the cyclic lipopeptide battacin, enabled by Cysteine Lipidation on a Peptide or Amino Acid (CLipPA) technology. Several of the novel "CLipP"ed lipopeptides exhibited low micromolar MICs and MBCs against both Gram-negative and Gram-positive bacteria. The mechanism of action was then simulated with the MIC data using computational methods.
View Article and Find Full Text PDFMembranes (Basel)
March 2021
Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, Żwirki i Wigury 101, 02-089 Warsaw, Poland.
The increasing resistance of bacteria to available antibiotics has stimulated the search for new antimicrobial compounds with less specific mechanisms of action. These include the ability to disrupt the structure of the cell membrane, which in turn leads to its damage. In this context, amphiphilic lipopeptides belong to the class of the compounds which may fulfill this requirement.
View Article and Find Full Text PDFAcc Chem Res
April 2021
School of Chemical Sciences The University of Auckland, 23 Symonds St, Auckland 1142, New Zealand.
The rise of multidrug resistant bacteria has significantly compromised our supply of antibiotics and poses an alarming medical and economic threat to society. To combat this problem, it is imperative that new antibiotics and treatment modalities be developed, especially those toward which bacteria are less capable of developing resistance. Peptide natural products stand as promising candidates to meet this need as bacterial resistance is typically slow in response to their unique modes of action.
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