Fig. 2

Vancomycin dependence phenotype and its reversion mechanisms. A Vancomycin induces the activation by phosphorylation of the histidine kinase-type membranal sensor VanS, which in turns phosphorylates the VanR. Phospho-VanR is then able to activate expression of its own operon and of the genes required for the biosynthesis of the alternative cell wall precursor required to resist vancomycin. Vancomycin-dependent strains display an inactivated ddl gene for which they cannot synthesize the original substrate, thus depending on the activation of the whole system provided by vancomycin to thrive. B Vancomycin dependence can be reversed by mutations restoring the production of the WT Ddl or by compensatory mutations restoring Ddl activity. C Vancomycin dependence can also be reversed by mutations causing antibiotic-independent expression of the vancomycin resistance genes. This can be accomplished by mutations producing constitutively active VanS which activates VanR in the absence of the activation signal (top), mutations leading to constitutively active VanR (middle) or mutations (indicated in green) eliminating an RNA terminator structure downstream the vanRS operon, allowing the leaky transcription of resistance genes from the upstream promoter (bottom)