In vivo increase in resistance to ciprofloxacin in Escherichia coli associated with deletion of the C-terminal part of MarR.
We recovered two isolates (EP1 and EP2) of Escherichia coli from the same patient that had identical pulsed-field gel electrophoresis patterns but required different MICs of ciprofloxacin (CIP): 16 and 256 mg/liter for EP1 and EP2, respectively. Both isolates had mutations in the quinolone resistance-determining regions of GyrA (Ser83Leu and Asp87Tyr) and ParC (Ser80Ile), but not in those regions of GyrB or ParE. Isolate EP2 was also more resistant to chloramphenicol, tetracyclines, cefuroxime, and organic solvents. A deletion of adenine (A) 1821 was found in marR of isolate EP2, which resulted in an 18-amino-acid C-terminal deletion in the MarR protein. The causative relationship between DeltaA1821 and the Mar phenotype was demonstrated both by the replacement of the wild-type marR by marR DeltaA1821 in isolate EP1 and by complementation with the wild-type marR in trans in isolate EP2. In isolate EP2 complemented with wild-type marR, susceptibility to chloramphenicol was restored completely, whereas susceptibility to CIP was restored only incompletely. Northern blotting demonstrated increased expression of marA and acrAB but not of soxS in isolate EP2 compared to EP1. In conclusion, the deletion of A1821 in marR in the clinical isolate EP2 caused an increase in the MICs of CIP and unrelated antibiotics. Presumably, the C-terminal part of MarR is necessary for proper repressor function.
Linde
H J
HJ
Institute for Medical Microbiology and Hygiene, University of Regensburg, Regensburg, Germany.
Notka
F
F
Metz
M
M
Kochanowski
B
B
Heisig
P
P
Lehn
N
N
D000890:Anti-Infective Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics* / Q000502:physiology; D002939:Ciprofloxacin / Q000494:pharmacology*; D004352:Drug Resistance, Microbial / Q000235:genetics / Q000502:physiology; D016521:Electrophoresis, Gel, Pulsed-Field; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins; D017353:Gene Deletion; D006801:Humans; D012097:Repressor Proteins / Q000235:genetics* / Q000502:physiology
D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; C080004:MarR protein, E coli; D012097:Repressor Proteins; D002939:Ciprofloxacin