Glycopeptide Antibiotic Resistance

Abstract

Glycopeptide antibiotics are integral components of the current antibiotic arsenal that is under strong pressures as a result of the emergence of a variety of resistance mechanisms over the past 15 years. Resistance has manifested itself largely through the expression of genes that encode proteins that reprogram cell wall biosynthesis and thus evade the action of the antibiotic in the enterococci, though recently new mechanisms have appeared that afford resistance and tolerance in the more virulent staphylococci and streptococci. Overcoming glycopeptide resistance will require innovative approaches to generate new antibiotics or otherwise to inhibit the action of resistance elements in various bacteria. The chemical complexity of the glycopeptides, the challenges of discovering and successfully exploiting new targets, and the growing number of distinct resistance types all increase the difficulty of the current problem we face as a result of the emergence of glycopeptide resistance.

Genome Sequence-Based Discriminator for Vancomycin-Intermediate Staphylococcus aureus

“…Indeed, VISA isolates appear to have thicker cell walls (12) along with an increase in the D-alanyl-D-alanine cell wall constituent residues, which are thought to be the target for the vancomycin glycopeptide, thereby reducing its efficacy (13). SNPs within several classes of cell wall-related genes have been associated with reduced vancomycin susceptibility, including a number of transcriptional regulators, agrA, agrC, and rpoB; members of two-component regulatory systems, vraSR, graSR, and walKR; penicillin binding proteins pbp4 and pbpB; and the phosphatase stp1 (10,(13)(14)(15)(16)(17)(18)(19)(20)(21).…”

Assembling the glycopeptide antibiotic scaffold: The biosynthesis of from Streptomyces toyocaensis NRRL15009

“…Clinical resistance to GPAs was first described in the enterococci in 1988 (3), and resistance has now manifested itself in the more virulent streptococci and staphylococci (reviewed in ref. 4). GPA resistance is now a significant worldwide phenomenon that has severely impacted the health care sector both in increased mortality and morbidity, and economically (5).…”

“…They are comprised of a heptapeptide core consisting of both common and unusual amino acids (4). Crosslinking of the amino acids through aryl ether and carbon-carbon bonds provides rigidity to the peptide.…”

N-acetylcysteine and vancomycin alone and in combination against staphylococci biofilm

“…NAC affects several processes that are important for bacterial biofilm formation on stainless steel surfaces, including a drastic reduction in extracellular polysaccharide production, and thus acts as an antibiofilm substance (Olofsson et al, 2003). On the other hand, vancomycin is a glycopeptide that inhibit cell wall synthesis of S. aureus and other Gram-positive organisms (Pootoolal et al, 2002). Then, the aim of this work was to determine the in vitro effect of two antimicrobial agents with different mode of action, alone and in combination, against biofilms of S. epidermidis and S. aureus.…”