Differential CTX-M Expression from a Conserved Promoter: Role of Promoter-Associated Spacer Sequences Downstream of the blaCTX-M Regulon

J Mol Microbiol Biotechnol. 2016;26(4):284-90. doi: 10.1159/000445950. Epub 2016 Jun 8.

Abstract

Aims: The aim of this project was to explore the different CTX-M expression levels occurring from a single conserved promoter with different spacer sequences, the variation of which is hypothesized to be a key factor in fluctuating levels of CTX-M.

Methods: The blaCTX-M promoter fragments with five different spacer sequences were amplified, sequenced and cloned into the pUA66 expression vector carrying the green fluorescent protein (GFP) gene. The expression of blaCTX-M in the transconjugants was analyzed using fluorescence microscopy, flow cytometry and qRT-PCR.

Results: The promoters of all the blaCTX-M genes were provided by ISEcp1 and were extremely conserved. The promoter-associated spacer sequences varied from 42 to 127 bp and variations in GFP expression in the five transconjugants were observed. A nucleic acid deletion and point mutation were detected in the spacer sequences by variations in which the expression of blaCTX-M was influenced.

Conclusion: The different spacer sequences have a significant impact on the activity of the conserved promoter. The shorter spacer sequence between the conserved promoter and the blaCTX-M gene does not specifically enhance the expression of blaCTX-M, contrary to previous reports. The expression of blaCTX-M may be regulated by changes in promoter activity caused by diverse spacer sequences.

MeSH terms

  • Flow Cytometry
  • Gene Expression Profiling
  • Gene Expression*
  • Genes, Reporter
  • Green Fluorescent Proteins / analysis
  • Green Fluorescent Proteins / genetics
  • Humans
  • Klebsiella Infections / microbiology
  • Klebsiella pneumoniae / enzymology
  • Klebsiella pneumoniae / isolation & purification
  • Microscopy, Fluorescence
  • Promoter Regions, Genetic*
  • Real-Time Polymerase Chain Reaction
  • beta-Lactamases / biosynthesis*
  • beta-Lactamases / genetics*

Substances

  • Green Fluorescent Proteins
  • beta-Lactamases