1887

Abstract

Primary antibiotic treatment of intestinal diseases requires metronidazole or vancomycin therapy. A cluster of genes homologous to enterococcal glycopeptides resistance genes was found in the genome of 630, although this strain remains sensitive to vancomycin. This -like gene cluster was found to consist of five ORFs: the regulatory region consisting of and and the effector region consisting of , and . We found that 57 out of 83 strains, representative of the main lineages of the species, harbour this -like cluster. The cluster is expressed as an operon and, when present, is found at the same genomic location in all strains. The , and homologues in 630 are co-transcribed and expressed to a low level throughout the growth phases in the absence of vancomycin. Conversely, the expression of these genes is strongly induced in the presence of subinhibitory concentrations of vancomycin, indicating that the -like operon is functional at the transcriptional level in . Hydrophilic interaction liquid chromatography (HILIC-HPLC) and MS analysis of cytoplasmic peptidoglycan precursors of 630 grown without vancomycin revealed the exclusive presence of a UDP-MurNAc-pentapeptide with an alanine at the C terminus. UDP-MurNAc-pentapeptide [-Ala] was also the only peptidoglycan precursor detected in grown in the presence of vancomycin, corroborating the lack of vancomycin resistance. Peptidoglycan structures of a -like mutant strain and of a strain lacking the -like cluster did not differ from the 630 strain, indicating that the -like cluster also has no impact on cell-wall composition.

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2013-07-01
2019-10-15
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