This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Enterococcus faecium, an opportunistic pathogen, causes a substantial proportion of enterococcal human infections, particularly in hospitals. Due to the intrinsic resistance that enterococci demonstrate towards many categories of antibiotics (e.g., penicillins), the most successful treatment has been glycopeptides. Glycopeptides cause bacterial cell death by perturbing the integrity of the cell wall. The most powerful glycopeptide, the so-called "drug of last resort," is vancomycin. However, the incidence of infections resistant to vancomycin has increased rapidly since 1988. Solving the problem of enterococcal resistance requires an understanding of the biosynthesis and organization of the cell-wall peptidoglycan, a potential binding site of vancomycin.