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      Synergistic Antimicrobial Activity Between the Broad Spectrum Bacteriocin Garvicin KS and Nisin, Farnesol and Polymyxin B Against Gram-Positive and Gram-Negative Bacteria

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      Current Microbiology
      Springer US
      Synergy effect, Bacteriocin, Garvicin KS, Antimicrobials, Pathogens

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          Abstract

          The increasing emergence of antibiotics resistance is of global concern. Finding novel antimicrobial agents and strategies based on synergistic combinations are essential to combat resistant bacteria. We evaluated the activity of garvicin KS, a new bacteriocin produced by Lactococcus garvieae. The bacteriocin has a broad inhibitory spectrum, inhibiting members of all the 19 species of Gram-positive bacteria tested. Unlike other bacteriocins from Gram-positive bacteria, garvicin KS inhibits Acinetobacter but not other Gram-negative bacteria. Garvicin KS was tested in combination with other antimicrobial agents. We demonstrated synergy with polymyxin B against Acinetobacter spp. and Escherichia coli, but not against Pseudomonas aeruginosa. Similar effects were seen with mixtures of nisin and polymyxin B. The synergistic mixtures of all three components caused rapid killing and full eradication of Acinetobacter spp. and E. coli. In addition, garvicin KS and nisin also acted synergistically against Staphylococcus aureus, indicating different in modes of action between the two bacteriocins. Both bacteriocins showed synergy with farnesol, and the combination of low concentrations of garvicin KS, nisin and farnesol caused rapid eradication of all the S. aureus strains tested. Its broad inhibitory spectrum, rapid killing, and synergy with other antimicrobials makes garvicin KS a promising antimicrobial.

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          Most cited references25

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          Outer membrane permeability and antibiotic resistance.

          To date most antibiotics are targeted at intracellular processes, and must be able to penetrate the bacterial cell envelope. In particular, the outer membrane of gram-negative bacteria provides a formidable barrier that must be overcome. There are essentially two pathways that antibiotics can take through the outer membrane: a lipid-mediated pathway for hydrophobic antibiotics, and general diffusion porins for hydrophilic antibiotics. The lipid and protein compositions of the outer membrane have a strong impact on the sensitivity of bacteria to many types of antibiotics, and drug resistance involving modifications of these macromolecules is common. This review will describe the molecular mechanisms for permeation of antibiotics through the outer membrane, and the strategies that bacteria have deployed to resist antibiotics by modifications of these pathways.
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            Toxicity of polymyxins: a systematic review of the evidence from old and recent studies

            Background The increasing problem of multidrug-resistant Gram-negative bacteria causing severe infections and the shortage of new antibiotics to combat them has led to the re-evaluation of polymyxins. These antibiotics were discovered from different species of Bacillus polymyxa in 1947; only two of them, polymyxin B and E (colistin), have been used in clinical practice. Their effectiveness in the treatment of infections due to susceptible Gram-negative bacteria, including Pseudomonas aeruginosa and Acinetobacter baumannii, has not been generally questioned. However, their use was abandoned, except in patients with cystic fibrosis, because of concerns related to toxicity. Methods We reviewed old and recent evidence regarding polymyxin-induced toxicity by searching Pubmed (from 1950 until May 2005). Results It was reported in the old literature that the use of polymyxins was associated with considerable toxicity, mainly nephrotoxicity and neurotoxicity, including neuromuscular blockade. However, recent studies showed that the incidence of nephrotoxicity is less common and severe compared to the old studies. In addition, neurotoxic effects of polymyxins are usually mild and resolve after prompt discontinuation of the antibiotics. Furthermore, cases of neuromuscular blockade and apnea have not been reported in the recent literature. Conclusion New evidence shows that polymyxins have less toxicity than previously reported. The avoidance of concurrent administration of nephrotoxic and/or neurotoxic drugs, careful dosing, as well as more meticulous management of fluid and electrolyte abnormalities and use of critical care services may be some of the reasons for the discrepancy between data reported in the old and recent literature.
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              Antimicrobial interactions: mechanisms and implications for drug discovery and resistance evolution.

              Combining antibiotics is a promising strategy for increasing treatment efficacy and for controlling resistance evolution. When drugs are combined, their effects on cells may be amplified or weakened, that is the drugs may show synergistic or antagonistic interactions. Recent work revealed the underlying mechanisms of such drug interactions by elucidating the drugs' joint effects on cell physiology. Moreover, new treatment strategies that use drug combinations to exploit evolutionary tradeoffs were shown to affect the rate of resistance evolution in predictable ways. High throughput studies have further identified drug candidates based on their interactions with established antibiotics and general principles that enable the prediction of drug interactions were suggested. Overall, the conceptual and technical foundation for the rational design of potent drug combinations is rapidly developing.
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                Author and article information

                Contributors
                +47 67232486 , helge.holo@nmbu.no
                Journal
                Curr Microbiol
                Curr. Microbiol
                Current Microbiology
                Springer US (New York )
                0343-8651
                1432-0991
                20 October 2017
                20 October 2017
                2018
                : 75
                : 3
                : 272-277
                Affiliations
                ISNI 0000 0004 0607 975X, GRID grid.19477.3c, Faculty of Chemistry, Biotechnology and Food Science, , Norwegian University of Life Sciences, ; POB 5003, 1432 Ås, Norway
                Article
                1375
                10.1007/s00284-017-1375-y
                5809525
                29058043
                ef001133-1f89-4679-b726-f4401479a640
                © The Author(s) 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 25 April 2017
                : 12 October 2017
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                © Springer Science+Business Media, LLC, part of Springer Nature 2018

                Microbiology & Virology
                synergy effect,bacteriocin,garvicin ks,antimicrobials,pathogens
                Microbiology & Virology
                synergy effect, bacteriocin, garvicin ks, antimicrobials, pathogens

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