Open AccessIn Vivo Increase in Resistance to Ciprofloxacin in Escherichia coli Associated with Deletion of the C-Terminal Part of MarR
Author(s) -
Hans-Jörg Linde,
Frank Notka,
Michaela Metz,
Bernd Kochanowski,
Peter Heisig,
Norbert Lehn
Publication year - 2000
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.44.7.1865-1868.2000
Subject(s) - complementation , escherichia coli , biology , microbiology and biotechnology , ciprofloxacin , chloramphenicol , nalidixic acid , wild type , phenotype , antibiotics , genetics , gene , mutant
We recovered two isolates (EP1 and EP2) ofEscherichia 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 inmarR of isolate EP2, which resulted in an 18-amino-acid C-terminal deletion in the MarR protein. The causative relationship between ΔA1821 and the Mar phenotype was demonstrated both by the replacement of the wild-typemarR bymarR ΔA1821 in isolate EP1 and by complementation with the wild-typemarR intrans in isolate EP2. In isolate EP2 complemented with wild-typemarR , susceptibility to chloramphenicol was restored completely, whereas susceptibility to CIP was restored only incompletely. Northern blotting demonstrated increased expression ofmarA andacrAB but not ofsoxS in isolate EP2 compared to EP1. In conclusion, the deletion of A1821 inmarR 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.