Genome-wide transcriptome analysis of fluoroquinolone resistance in clinical isolates of Escherichia coli

Int J Urol. 2012 Apr;19(4):360-8. doi: 10.1111/j.1442-2042.2011.02933.x. Epub 2011 Dec 29.

Abstract

Objectives: Coincident with their worldwide use, resistance to fluoroquinolones in Escherichia coli has increased. To identify the gene expression profiles underlying fluoroquinolone resistance, we carried out genome-wide transcriptome analysis of fluoroquinolone-sensitive E. coli.

Methods: Four fluoroquinolone-sensitive E. coli and five fluoroquinolone-resistant E. coli clinical isolates were subjected to complementary deoxyribonucleic acid microarray analysis. Some upregulated genes' expression was verified by real-time polymerase chain reaction using 104 E. coli clinical isolates, and minimum inhibitory concentration tests were carried out by using their transformants.

Results: A total of 40 genes were significantly upregulated in fluoroquinolone-resistant E. coli isolates (P < 0.05). The expression of phage shock protein operons, which are involved in biofilm formation, was markedly upregulated in our profile of fluoroquinolone-resistant E. coli. One of the phage shock protein operons, pspC, was significantly upregulated in 50 fluoroquinolone-resistant E. coli isolates (P < 0.0001). The expression of type I fimbriae genes, which are pilus operons involved in biofilm formation, were markedly downregulated in fluoroquinolone-resistant E. coli. Deoxyribonucleic acid adenine methyltransferase (dam), which represses type I fimbriae genes, was significantly upregulated in the clinical fluoroquinolone-resistant E. coli isolates (P = 0.007). We established pspC- and dam-expressing E. coli transformants from fluoroquinolone-sensitive E. coli, and the minimum inhibitory concentration tests showed that the transformants acquired fluoroquinolone resistance, suggesting that upregulation of these genes contributes to acquiring fluoroquinolone resistance.

Conclusions: Upregulation of psp operones and dam underlying pilus operons downregulation might be associated with fluoroquinolone resistance in E. coli.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Child
  • Child, Preschool
  • Ciprofloxacin / pharmacology
  • Ciprofloxacin / therapeutic use
  • Drug Resistance, Bacterial / genetics
  • Escherichia coli / drug effects*
  • Escherichia coli / genetics*
  • Escherichia coli Infections / drug therapy*
  • Escherichia coli Infections / genetics*
  • Female
  • Fluoroquinolones / pharmacology*
  • Fluoroquinolones / therapeutic use
  • Gene Expression Regulation, Bacterial / drug effects
  • Genome, Bacterial
  • Humans
  • Infant
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Ofloxacin / pharmacology
  • Ofloxacin / therapeutic use
  • Transcriptome
  • Young Adult

Substances

  • Anti-Bacterial Agents
  • Fluoroquinolones
  • Ciprofloxacin
  • Ofloxacin