Prior to the introduction of linezolid and synercid, VRE
were the first hospital bacteria to become resistant to all
available antibiotics. These organisms, often identified
as commensals of the human gastrointestinal tract, were
found to be the second most prevalent pathogen in
intensive care units in the United States. The vancomycin
resistance was initially identified to be conferred by an
operon of eight genes (Figure 1). Vancomycin resistance
is known to be transferable [2] and many transferable
resistance mechanisms are the result of single genes;
vancomycin resistance thus showed a quantum leap in
the sophistication of resistance determinants. The original
operon was bound by insertion sequences encoding
transposon Tn1546 [3]. The two genes of a classic class II
transposon ensure the migration of the gene between
replicons and different strains. Three essential genes
(vanH, vanA and vanX) are responsible for initiating an
alternative route to peptidoglycan synthesis that removes
the glycopeptide binding site of the D-alanyl-D-alanine
group on the pentapeptide. This alternative route involves
reversing the formation of the D-alanyl-D-alanine
moiety (VanX) to release free D-alanine, hydrogenating
pyruvate to form lactate (VanH), which is then ligated
with the freed D-alanine to provide D-alanyl-lactate