The main mechanism of resistance against vancomycin consists in the mutation of the terminal dipeptide in lipid II from D-Ala-D-Ala to D-Ala-D-Lac (shown in Figure and D, respectively), and emerged in Vancomycin Resistant Enterococcus (VRE) . This structural change eliminates one of the five hydrogen bonds between vancomycin and its target and increases the dissociation constant (Kd) by approximately 1,000-fold . This small yet significant change underscores how minor structural alterations can drastically impact antibiotic potency.