title: Expression of marA is remarkably increased from the early stage of development of fluoroquinolone-resistance in uropathogenic Escherichia coli.
abstract: BACKGROUND
  Analyses of efflux pumps overexpression and mutations in quinolone resistance determining region (QRDR) in early stage of development of resistance to fluoroquinolones (FQs) are valuable to discuss countermeasures against them. We induced levofloxacin (LVFX)-resistant strains from susceptible uropathogenic Escherichia coli in vitro to analyze the mechanisms of development of FQs-resistance.
  
  
  METHODS
  89 strains were exposed to discontinuous elevation of LVFX dose, and mRNA level of efflux pumps and their regulators as well as mutations developed in QRDR of LVFX-resistant strains were analyzed.
  
  
  RESULTS
  In 5 strains, a stepwise increase in MIC to LVFX (up to >128 μg/ml)was observed. Compared to the parent strains, additional mutations in QRDR were observed in the strains developing high MIC. Remarkable increase of marA expression was observed even in the early stage of LVFX-resistance development, and it lasted until high-level resistance was developed. On the other hand, moderate increase in acrB expression but only low increase in yhiU, yhiV, mdfA, tolC and sdiA were observed.
  
  
  CONCLUSIONS
  These results suggested that marA expression is a sensitive marker for early detection of development of LVFX-resistance.
authors.affiliation: Division of Food Hygiene, Department of Animal and Food Hygiene, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan. Electronic address: yamasakie@obihiro.ac.jp.
authors.forename: Eiki
authors.initials: E
authors.lastname: Yamasaki
authors.affiliation: The Department of Urology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Yamada
authors.affiliation: The Department of Urology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Xinghua
authors.initials: X
authors.lastname: Jin
authors.affiliation: Translational Health Science and Technology Institute, Gurgaon, Haryana, India.
authors.forename: G Balakrish
authors.initials: GB
authors.lastname: Nair
authors.affiliation: Division of Food Hygiene, Department of Animal and Food Hygiene, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Kurazono
authors.affiliation: The Department of Urology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Yamamoto
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D004927:Escherichia coli Infections / Q000382:microbiology; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D024841:Fluoroquinolones / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D056689:Uropathogenic Escherichia coli / Q000187:drug effects* / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D024841:Fluoroquinolones; C080002:MarA protein, E coli
keywords: Efflux pump; Fluoroquinolones-resistant Escherichia coli; Quinolone resistant determining region; Urinary tract infection