Vancomycin-dependent enterococci

An interesting phenomenon that has developed in some strains of VanA- and VanB-type VRE is that of vancomycin dependence. These enterococci are not just resistant to vancomycin but now require it for growth. Vancomycin-dependent enterococci have been recovered from apparently culture-negative clinical samples by plating them onto vancomycin-containing agar, such as that used for isolation of Campylobacter or gonococci. A likely explanation for the phenomenon of vancomycin dependence is that these enterococci turn off their normal production of D-Ala–D-Ala and then can grow only if a substitute dipeptide like structure is made. With most VanA- and VanB-type enterococci, this occurs only in the presence of vancomycin, which induces the synthesis of associated dehydrogenase (VanH) and ligase (VanA or VanB) that make D-Ala–D-Lac. The reason for the cell turning off the synthesis of D-Ala–D-Ala is that as long as vancomycin is present, D-Ala–D-Ala is not necessary for cell wall synthesis by VRE. Indeed, it is being destroyed by the action of VanX. Once the vancomycin is removed, D-Ala–D-Lac is no longer synthesized, and without either D-Ala–D-Ala or D-Ala–D-Lac, the cell cannot continue to grow or replicate. Reversion to vancomycin independence has been observed; it probably occurs by either a mutation that leads to constitutive production of D-Ala–D-Lac or one that restores the synthesis of D-Ala–D-Ala. Case reports, however, describe nosocomial infections caused by enterococci that require vancomycin for growth.