antibiotics shaping bacterial genome deletion of an is91 flanked virulence determinant upon exposure to subinhibitory antibiotic concentrations抗生素形成细菌基因组的删除is91在毒性行列式在接触subinhibitory抗生素浓度.pdfVIP

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antibiotics shaping bacterial genome deletion of an is91 flanked virulence determinant upon exposure to subinhibitory antibiotic concentrations抗生素形成细菌基因组的删除is91在毒性行列式在接触subinhibitory抗生素浓度.pdf

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antibiotics shaping bacterial genome deletion of an is91 flanked virulence determinant upon exposure to subinhibitory antibiotic concentrations抗生素形成细菌基因组的删除is91在毒性行列式在接触subinhibitory抗生素浓度

Antibiotics Shaping Bacterial Genome: Deletion of an IS91 Flanked Virulence Determinant upon Exposure to Subinhibitory Antibiotic Concentrations ´ 1 ˜ 1 2 2 2 ´ 1,2 Laura Pedro , Rosa C. Banos , Sonia Aznar , Cristina Madrid , Carlos Balsalobre , Antonio Juarez * ´ 1 Institut de Bioenginyeria de Catalunya, Parc Cientıfic de Barcelona, Barcelona, Spain, 2 Departament de Microbiologia, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain Abstract The nucleoid-associated proteins Hha and YdgT repress the expression of the toxin a-hemolysin. An Escherichia coli mutant lacking these proteins overexpresses the toxin a-hemolysin encoded in the multicopy recombinant plasmid pANN202-312R. Unexpectedly, we could observe that this mutant generated clones that no further produced hemolysin (Hly-). Generation of Hly- clones was dependent upon the presence in the culture medium of the antibiotic kanamycin (km), a marker of the hha allele (hha::Tn5). Detailed analysis of different Hly- clones evidenced that recombination between partial IS91 sequences that flank the hly operon had occurred. A fluctuation test evidenced that the presence of km in the culture medium was underlying the generation of these clones. A decrease of the km concentration from 25 mg/l to 12.5 mg/l abolished the appearance of Hly- derivatives. We considered as a working hypothesis that, when producing high levels of the toxin (combination of the hha ydgT mutations with the presence of the multicopy hemolytic plasmid pANN202-312R), the concentration of km of 25 mg/l resulted subinhibitory and stimulat