Abstract
The glycopeptide vancomycin was until recently considered a drug of last resort against Gram-positive bacteria. Increasing numbers of bacteria, however, are found to carry genes that confer resistance to this antibiotic. So far, 10 different vancomycin resistance clusters have been described. A chromosomal vancomycin resistance gene cluster was previously described for the anaerobic Desulfitobacterium hafniense Y51. We demonstrate that this gene cluster, characterized by its d-Ala-d-Lac ligase-encoding vanI gene, is present in all strains of D. hafniense, D. chlororespirans and some strains of Desulfosporosinus spp. This gene cluster was not found in vancomycin-sensitive Desulfitobacterium or Desulfosporosinus spp., and we show that this antibiotic resistance can be exploited as an intrinsic selection marker for Desulfitobacterium hafniense and D. chlororespirans. The gene cluster containing vanI is phylogenetically only distantly related with those described from soil and gut bacteria, but clusters instead with vancomycin resistance genes found within the phylum Actinobacteria that include several vancomycin-producing bacteria. It lacks a vanH homologue, encoding a D-lactate dehydrogenase, previously thought to always be present within vancomycin resistance gene clusters. The location of vanH outside the resistance gene cluster likely hinders horizontal gene transfer. Hence, the vancomycin resistance cluster in D. hafniense should be regarded a novel one that we here designated vanI after its unique d-Ala-d-Lac ligase.
Highlights
Chromosomal DNA was isolated from 13 Desulfitobacterium spp. strains, covering the majority of the currently described species of this genus
All nine polymerase chain reaction (PCR)-positive isolates were strains of D. hafniense, with the exception of D. chlororespirans, which is the closest relative of D. hafniense based on 16S rRNA gene similarity (Fig. 2)
It is clear that the D-Ala-D-Lac ligase gene found in Desulfitobacterium spp. and Desulfosporosinus spp. does not belong to the vanA cluster, but instead is part of a distinct vancomycin resistance cluster, which we propose to name vanI after its unique D-Ala-D-Lac ligase
Summary
The glycopeptides vancomycin and teicoplanin are widely used antibiotics for treatment of infections with Gram-positive bacteria. They act by binding to the D-alanyl-D-alanine (D-Ala-D-Ala) terminus of intermediates in peptidoglycan formation, thereby inhibiting cell wall cross-linking (Courvalin, 2006). Vancomycin resistance is classified into clusters based on the DNA sequence of the ligase gene vanA and its homologues that encode the key enzyme in the synthesis of D-Ala-D-Lac or D-Ala-D-Ser. Currently, 10 different types of vancomycin resistance gene clusters have been identified. D-Ala-D-Lac type resistance is associated with clusters vanA, vanB, vanD, vanF and vanM, whereas D-Ala-D-Ser resistance is linked to clusters vanC, vanE, vanG, vanL and vanN (Fraimow et al, 2005; Depardieu et al, 2007; Boyd et al, 2008; Xu et al, 2010; Lebreton et al, 2011). The vanA cluster confers a high level of resistance to teicoplanin, whereas the other gene clusters of the D-Ala-D-Lac type give less or no resistance to teicoplanin (Kalan et al, 2009; Xu et al, 2010)
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