TABLE 1.
Major mutational variants detected in the course of the experimental evolution of ciprofloxacin resistancea
Target(s) |
E. coli |
A. baumannii |
P. aeruginosa |
||||||
---|---|---|---|---|---|---|---|---|---|
Variant | Max. freq. (%)b | No. of reactors (out of 10) | Variant | Max. freq. (%)b | No. of reactors (out of 5) | Variant | Max. freq. (%)b | No. of reactors (out of 12) | |
Primary | |||||||||
GyrA, DNA gyrase subunit A | Ser83Leu | 98 | 1 | Ser81Leu | 99 | 5 | Thr83Ile | 100 | 12 |
Asp87Asn | 17 | 1 | Asp87Asn | 79 | 2 | ||||
Asp87Tyr | 99 | 4 | Asp87Tyr | 52 | 1 | ||||
Asp87Gly | 74 | 6 | |||||||
Ala119Glu | 7 | 2 | |||||||
GyrB, DNA gyrase subunit B | Ser464Phe | 96 | 6 | Leu128Pro | 7 | 1 | |||
Ser464Tyr | 99 | 4 | Ser466Phe | 63 | 4 | ||||
Secondary | |||||||||
ParC, topoisomerase IV subunit A | Ser84Leu | 36 | 4 | Ser87Leu | 53 | 6 | |||
Glu88Lys | 86 | 2 | |||||||
Asn334Tyr | 4 | 1 | |||||||
ParE, topoisomerase IV subunit B | Leu121Pro | 8 | 1 | ||||||
Ser457Gly | 6 | 1 | |||||||
Ser457Cys | 17 | 1 | |||||||
Ser457_insArg | 9 | 1 | |||||||
Val460Gly | 62 | 2 | |||||||
Efflux pump deregulation | marRc | 86 | 9 | adeNc | 28 | 5 | nfxBc | 90 | 12 |
soxRc | 95 | 9 | adeSc | 72 | 4 | us_mexE | 39 | 1 | |
us_soxS | 10 | 2 | us_adeI | 36 | 4 | us_mexT | 12 | 5 | |
acrRc | 63 | 9 | mexT:G58D | 6 | 1 | ||||
us_acrA | 53 | 3 | mexSc | 94 | 7 | ||||
Other strongly implicated genes | pilBOPQRSTWZc | 98 | 11 | ||||||
mutLc | 37 | 2 | |||||||
mutSc | 27 | 3 |
Listed mutations that reached ≥5% in at least in one reactor and one time point.
Maximum observed frequency reached at any time point in any reactor.
Disruptive mutations (mainly frameshifts, stops, small indels, and IS elements).