Fig 1.
Spontaneous mutation rate per 108 cells to quinolone resistance among E. coli K-12 (MG1655).
Mutation rates were estimated from 30 independent cultures at 1x and 2x MIC. Error bars represent 95% confidence intervals. Note that no colonies were obtained at 2xMIC for Nal.
Table 1.
Spontaneous mutation rates to quinolone resistance in E. coli K-12 (MG1655).
Fig 2.
The domain structures of Gyrase A, B, and MarR.
Mutations obtained in this study are indicated in bold above. Panel A: Arrangement of GyrA. This subunit of DNA gyrase consists of the breakage-reunion (BRD) domain, and the quinolone resistance determining region (QRDR-A) site. Panel B: Arrangement of GyrB, with the ATPase, Transducer (221–392), and Toprim (418–533) regions. The QRDR-B is shown within the Toprim domain of GyrB [73]. Panel C. MarR domain structure, comprising four helices (H) and three ß-sheets (B). H3 and H4 (57–80) are the recognition and DNA binding motifs containing H-T-H motifs and the ß-sheet winged structure. H1, H5, and H6 are associated with dimerization [42,74–76].
Table 2.
MIC fold-increase and mutations in gyrA, gyrB and marR among nalR, cipR, and levoR mutants of E. coli K-12 (MG1655).
Fig 3.
Direct responses to selection.
Changes in MIC for resistant mutants towards the drug on which they were selected: nal (A), cip (B), and levo (C). The boxplot presents the median, first, and third quartiles, with whiskers showing either the maximum (minimum) value or 1.5 times the interquartile range of the data, whichever is smaller (larger).
Table 3.
Two-way analysis of variance (ANOVA) for the effects of antibiotic and gene on levels of resistance.
Fig 4.
Cross-resistance between antibiotics.
Fold-increase in MIC of resistant mutants isolated on nal (A), cip (B), and levo (C) against all three antibiotics. The boxplot presents the median, first, and third quartiles, with whiskers showing either the maximum (minimum) value or 1.5 times the interquartile range of the data, whichever is smaller (larger).
Fig 5.
Costs of resistance of quinolone resistant mutants.
The fitness components measured are growth rate, cell density, and lag time between gyrA, gyrB, and marR resistance mutations. All the fitness components are compared to control E. coli K-12 (MG1655). The boxplot presents the median, first, and third quartiles, with whiskers showing either the maximum (minimum) value or 1.5 times the interquartile range of the data, whichever is smaller (larger).
Table 4.
Effects of resistance mutations on growth parameters.
Fig 6.
No correlation between level of resistance (fold-increase in MIC) and growth rate, cell density or length of lag phase for all mutants.