Global responses to oxytetracycline treatment in tetracycline-resistant Escherichia coli
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Global responses to oxytetracycline treatment in tetracycline-resistant Escherichia coli. / Møller, Thea S.B.; Liu, Gang; Hartman, Hassan B.; Rau, Martin H.; Mortensen, Sisse; Thamsborg, Kristian; Johansen, Andreas E.; Sommer, Morten O.A.; Guardabassi, Luca; Poolman, Mark G.; Olsen, John E.
In: Scientific Reports, Vol. 10, No. 1, 8438, 2020.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Global responses to oxytetracycline treatment in tetracycline-resistant Escherichia coli
AU - Møller, Thea S.B.
AU - Liu, Gang
AU - Hartman, Hassan B.
AU - Rau, Martin H.
AU - Mortensen, Sisse
AU - Thamsborg, Kristian
AU - Johansen, Andreas E.
AU - Sommer, Morten O.A.
AU - Guardabassi, Luca
AU - Poolman, Mark G.
AU - Olsen, John E.
PY - 2020
Y1 - 2020
N2 - We characterized the global transcriptome of Escherichia coli MG1655:: tetA grown in the presence of ½ MIC (14 mg/L) of OTC, and for comparison WT MG1655 strain grown with 1//2 MIC of OTC (0.25 mg/L OTC). 1646 genes changed expression significantly (FDR > 0.05) in the resistant strain, the majority of which (1246) were also regulated in WT strain. Genes involved in purine synthesis and ribosome structure and function were top-enriched among up-regulated genes, and anaerobic respiration, nitrate metabolism and aromatic amino acid biosynthesis genes among down-regulated genes. Blocking of the purine-synthesis- did not affect resistance phenotypes (MIC and growth rate with OTC), while blocking of protein synthesis using low concentrations of chloramphenicol or gentamicin, lowered MIC towards OTC. Metabolic-modeling, using a novel model for MG1655 and continuous weighing factor that reflected the degree of up or down regulation of genes encoding a reaction, identified 102 metabolic reactions with significant change in flux in MG1655:: tetA when grown in the presence of OTC compared to growth without OTC. These pathways could not have been predicted by simply analyzing functions of the up and down regulated genes, and thus this work has provided a novel method for identification of reactions which are essential in the adaptation to growth in the presence of antimicrobials.
AB - We characterized the global transcriptome of Escherichia coli MG1655:: tetA grown in the presence of ½ MIC (14 mg/L) of OTC, and for comparison WT MG1655 strain grown with 1//2 MIC of OTC (0.25 mg/L OTC). 1646 genes changed expression significantly (FDR > 0.05) in the resistant strain, the majority of which (1246) were also regulated in WT strain. Genes involved in purine synthesis and ribosome structure and function were top-enriched among up-regulated genes, and anaerobic respiration, nitrate metabolism and aromatic amino acid biosynthesis genes among down-regulated genes. Blocking of the purine-synthesis- did not affect resistance phenotypes (MIC and growth rate with OTC), while blocking of protein synthesis using low concentrations of chloramphenicol or gentamicin, lowered MIC towards OTC. Metabolic-modeling, using a novel model for MG1655 and continuous weighing factor that reflected the degree of up or down regulation of genes encoding a reaction, identified 102 metabolic reactions with significant change in flux in MG1655:: tetA when grown in the presence of OTC compared to growth without OTC. These pathways could not have been predicted by simply analyzing functions of the up and down regulated genes, and thus this work has provided a novel method for identification of reactions which are essential in the adaptation to growth in the presence of antimicrobials.
U2 - 10.1038/s41598-020-64995-1
DO - 10.1038/s41598-020-64995-1
M3 - Journal article
C2 - 32439837
AN - SCOPUS:85085156733
VL - 10
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 8438
ER -
ID: 242303548