Mechanism of action
Vancomycin acts by inhibiting proper cell wall synthesis in Gram-positive bacteria. Due to the different mechanism by which Gram-negative bacteria produce their cell walls and the various factors related to entering the outer membrane of Gram-negative organisms, vancomycin is not active against them (except some nongonococcal species of Neisseria). The large hydrophilic molecule is able to form hydrogen bond interactions with the terminal D-alanyl-D-alanine moieties of the NAM/NAG-peptides. Under normal circumstances, this is a five-point interaction. This binding of vancomycin to the D-Ala-D-Ala prevents cell wall synthesis of the long polymers of N-acetylmuramic acid (NAM) and N-acetylglucosamine (NAG) that form the backbone strands of the bacterial cell wall, and it prevents the backbone polymers that do manage to form from cross-linking with each other. Plant tissue culture
Vancomycin is one of the few antibiotics used in plant tissue culture to eliminate Gram-positive bacterial infection. It has relatively low toxicity to plants. Antibiotic resistance
Intrinsic resistance
A few Gram-positive bacteria are intrinsically resistant to vancomycin: Leuconostoc and Pediococcus species, but these organisms rarely cause diseases in humans. Most Lactobacillus species are also intrinsically resistant to vancomycin, with the exception of L. acidophilus and L. delbrueckii, which are sensitive. Other Gram-positive bacteria with intrinsic resistance to vancomycin include Erysipelothrix rhusiopathiae, Weissella confusa, and Clostridium innocuum.Most Gram-negative bacteria are intrinsically resistant to vancomycin because their outer membranes are impermeable to large glycopeptide molecules (with the exception of some non-gonococcal Neisseria species). Acquired resistance
Evolution of microbial resistance to vancomycin is a growing problem, in particular, within healthcare facilities such as hospitals.
Three main resistance variants have been characterised to date among resistant Enterococcus faecium and E. faecalis populations:

VanA - enterococcal resistance to vancomycin and teicoplanin; inducible on exposure to these agents
VanB - lower-level enterococcal resistance; inducible by vancomycin, but strains may remain susceptible to teicoplanin
VanC - least clinically important; enterococci resistant only to vancomycin; constitutive resistanceVariant of vancomycin has been tested that binds to the resistant D-lactic acid variation in vancomycin-resistant bacterial cell walls, and also binds well to the original target (vancomycin-susceptible bacteria). "Re-gained" vancomycin
In 2020 a team at the University Hospital Heidelberg (Germany) re-gained the antibacterial power of vancomycin by modifying the molecule with a cationic oligopeptide. The oligopeptide consists of six arginin units in Position VN. In comparison to the unmodified vancomycin the activity against vancomycin-resistant bacteria could be enhanced by a factor of 1 000. This pharmacon is still in preclinical development. Therefore, a potential approval will take several more years. History
Vancomycin was first isolated in 1953 by Edmund Kornfeld (working at Eli Lilly) from a soil sample collected from the interior jungles of Borneo by a missionary, Rev. William M. Bouw (1918-2006). The organism that produced it was eventually named Amycolatopsis orientalis. The original indication for vancomycin was for the treatment of penicillin-resistant Staphylococcus aureus.The compound was initially called compound 05865, but was eventually given the generic name vancomycin, derived from the term "vanquish". One advantage that was quickly apparent was that staphylococci did not develop significant resistance, despite serial passage in culture media containing vancomycin.