Insertion of a Novel DNA Sequence, 1S1186, Upstream of the Silent Carbapenemase Gene cfiA, Promotes Expression of Carbapenem Resistance in Clinical Isolates of Bacteroides Fragilis

Mol Microbiol. 1994 Apr;12(1):105-14. doi: 10.1111/j.1365-2958.1994.tb00999.x.


A small number of isolates of Bacteroides fragilis, an anaerobic pathogen of the human intestinal flora, carries a copy (or copies) of the carbapenemresistance gene, cfiA, which may be silent or expressed. We have studied the mechanism of activation of the frequently silent gene in in vitro-selected mutants and in clinical isolates. In both types of strains, activation was observed as the consequence of the insertion, at several possible sites, of a novel 1.3 kb insertion sequence, IS1186, immediately upstream of the carbapenemase gene. IS1186 has two open reading frames, on opposite strands, with coding capacities for a 41.2 kDa (ORF1) and a 22.5kDa (ORF2) protein. The 41.2kDa protein has homology with some proteins predicted from open reading frames of IS elements or DNA direct repeats of aerobic, but not anaerobic, Gram-negative bacteria. Upon insertion, transcription of cfiA was found to be driven from a promoter identified on the right end of IS1186. In one instance, insertion occurred into the putative ribosome-binding site of cfiA, leaving intact the tetranucleotide AGAA which is concluded to be a fully functional ribosome-binding site. Between 3 and 14 copies of IS1186 were detected per genome and the element was found, within the species B. fragilis, almost exclusively in the subgroup carrying the cifA gene.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / biosynthesis*
  • Bacterial Proteins / genetics
  • Bacteroides fragilis / drug effects
  • Bacteroides fragilis / genetics*
  • Base Sequence
  • Carbapenems / pharmacology*
  • Cloning, Molecular
  • DNA Transposable Elements*
  • Drug Resistance, Microbial / genetics
  • Enzyme Induction
  • Gene Expression Regulation, Bacterial*
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • Ribosomes / metabolism
  • Transcription, Genetic
  • beta-Lactamases / biosynthesis*
  • beta-Lactamases / genetics


  • Bacterial Proteins
  • Carbapenems
  • DNA Transposable Elements
  • beta-Lactamases
  • carbapenemase

Associated data

  • GENBANK/X72300
  • GENBANK/X72301