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      Bacterial aggregation triggered by low-level antibiotic-mediated lysis

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          Abstract

          Suspended bacterial aggregates play a central role in ocean biogeochemistry, industrial processes and probably many clinical infections – yet the factors that trigger aggregation remain poorly understood, as does the relationship between suspended aggregates and surface-attached biofilms. Here we show that very low doses of cell-wall targeting antibiotic, far below the minimal inhibitory concentration, can trigger aggregation of Escherichia coli cells. This occurs when a few cells lyse, releasing extracellular DNA – thus, cell-to-cell variability in antibiotic response leads to population-level aggregation. Although lysis-triggered aggregation echoes known trigger mechanisms for surface-attached biofilms, these aggregates may have different ecological implications since they do not show increased biofilm-forming potential or increased antibiotic resistance. Our work contributes to understanding the nature of bacterial aggregates and the factors that trigger their formation, and the possible consequences of widespread low-dose antibiotic exposure in the environment and in the body.

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          Most cited references65

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          Microbiological effects of sublethal levels of antibiotics.

          The widespread use of antibiotics results in the generation of antibiotic concentration gradients in humans, livestock and the environment. Thus, bacteria are frequently exposed to non-lethal (that is, subinhibitory) concentrations of drugs, and recent evidence suggests that this is likely to have an important role in the evolution of antibiotic resistance. In this Review, we discuss the ecology of antibiotics and the ability of subinhibitory concentrations to select for bacterial resistance. We also consider the effects of low-level drug exposure on bacterial physiology, including the generation of genetic and phenotypic variability, as well as the ability of antibiotics to function as signalling molecules. Together, these effects accelerate the emergence and spread of antibiotic-resistant bacteria among humans and animals.
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            Distinguishing between resistance, tolerance and persistence to antibiotic treatment.

            Antibiotic tolerance is associated with the failure of antibiotic treatment and the relapse of many bacterial infections. However, unlike resistance, which is commonly measured using the minimum inhibitory concentration (MIC) metric, tolerance is poorly characterized, owing to the lack of a similar quantitative indicator. This may lead to the misclassification of tolerant strains as resistant, or vice versa, and result in ineffective treatments. In this Opinion article, we describe recent studies of tolerance, resistance and persistence, outlining how a clear and distinct definition for each phenotype can be developed from these findings. We propose a framework for classifying the drug response of bacterial strains according to these definitions that is based on the measurement of the MIC together with a recently defined quantitative indicator of tolerance, the minimum duration for killing (MDK). Finally, we discuss genes that are associated with increased tolerance - the 'tolerome' - as targets for treating tolerant bacterial strains.
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              Microtitre plate-based antibacterial assay incorporating resazurin as an indicator of cell growth, and its application in the in vitro antibacterial screening of phytochemicals

              The resazurin assay utilising microtitre-plate, described by Drummond and Waigh in 2000, has been modified to achieve more accuracy in the determination of the minimum inhibitory concentration (MIC) values of natural products, including crude extracts, chromatographic fractions or purified compounds against various bacterial strains. This modified resazurin method is simple, sensitive, rapid, robust and reliable, and could be used successfully to assess antibacterial properties of natural products.
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                Author and article information

                Contributors
                rosalind.allen@uni-jena.de
                Journal
                NPJ Biofilms Microbiomes
                NPJ Biofilms Microbiomes
                NPJ Biofilms and Microbiomes
                Nature Publishing Group UK (London )
                2055-5008
                26 September 2024
                26 September 2024
                2024
                : 10
                : 90
                Affiliations
                [1 ]School of Physics and Astronomy, University of Edinburgh, ( https://ror.org/01nrxwf90) Edinburgh, UK
                [2 ]Theoretical Microbial Ecology, Institute of Microbiology, Faculty of Biological Sciences, Friedrich Schiller University Jena, ( https://ror.org/05qpz1x62) Jena, Germany
                [3 ]Cluster of Excellence Balance of the Microverse, Friedrich Schiller University Jena, ( https://ror.org/05qpz1x62) Jena, Germany
                Author information
                http://orcid.org/0000-0003-4110-2962
                Article
                553
                10.1038/s41522-024-00553-1
                11427687
                39327479
                997f3ef7-bc5f-4c7f-b47a-91b987715901
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 11 November 2023
                : 20 August 2024
                Funding
                Funded by: FundRef 100010663, EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council);
                Award ID: 682237
                Funded by: FundRef 501100000268, RCUK | Biotechnology and Biological Sciences Research Council (BBSRC);
                Award ID: BB/R012415/1
                Funded by: FundRef 501100001659, Deutsche Forschungsgemeinschaft (German Research Foundation);
                Award ID: 390713860
                Funded by: FundRef 100010687, EC | EU Framework Programme for Research and Innovation H2020 | H2020 Euratom (H2020 Euratom Research and Training Programme 2014-2018);
                Award ID: 682237
                Funded by: FundRef 100010687, EC | EU Framework Programme for Research and Innovation H2020 | H2020 Euratom (H2020 Euratom Research and Training Programme 2014-2018);
                Award ID: 682237
                Categories
                Article
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                © Springer Nature Limited 2024

                biofilms,antimicrobials
                biofilms, antimicrobials

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