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. 2017 Jul 19;7:5860. doi: 10.1038/s41598-017-06289-7

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© The Author(s) 2017

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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

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c-di-GMP increases M.sm resistance to ETH. (a). Antibioctic sensitive assay for the effects of c-di-GMP on different antibiotics. Different strains grew in serially diluted (128–0.125 μg/mL) antibiotics, i.e. ethionamide (ETH), rifampicin (RFP), or isoniazidea (INH). MIC represent the lowest concentration of drug under which strains can grow. (b). Time-Kill curve for M.sm during 60 h. The curve is depicted by the growth of M.sm-pMV261 and M.sm-pMV261-dgc under 120 μg/mL ETH at interval of 12 h. The concetration of ETH chosed is 15-fold MIC of M.sm-pMV261. (c,d). Growth curve for M.sm under 6 μg/mL during 60 h. The curves are depicted by the growth of M.sm-pMV261, M.sm-pMV261-dgc, M.sm-pMV261-ethr, and M.sm-ethr::hyg under 6 μg/mL ETH at interval of 12 h (c) and by the growth of M.sm-ethr::hyg-pMV261, M.sm-ethr::hyg-pMV261-dgc, M.sm-ethr::hyg-pMV261-ethr under 6 μg/mL ETH at interval of 12 h (d). Means ± standard deviation (S.D.) represent the variant range of the data derived from three biological replicates.