Renaissance of vancomycin: approaches for breaking antibiotic resistance in multidrug-resistant bacteria

Abstract

The emergence of multidrug-resistant bacteria demands innovations in the development of new antibiotics. For decades, the glycopeptide antibiotic vancomycin has been considered as the “last resort” treatment of severe infections caused by Gram-positive bacteria. Since the discovery of the first vancomycin-resistant enterococci strains in the late 1980s, the number of resistances has been steadily rising, with often life-threatening consequences. As an alternative to the generation of completely new substances, novel approaches focus on structural modifications of established antibiotics such as vancomycin to overcome these resistances. Here, we provide an overview of several promising modifications of vancomycin to restore its efficacy against vancomycin-resistant enterococci.

Exploring Beneficial Properties of the Bacteriocinogenic Enterococcus faecium ST10Bz Strain Isolated from Boza, a Bulgarian Cereal-Based Beverage

“…Enterococcus strains were generally considered as “prepared” for the antibiotic era, as they usually carry resistance genes intrinsic to their genetic make-up, reducing their sensitivity to a wide range of antibiotics and biocides [ 71 , 72 ]. The emergence of a specific group of (mainly nosocomial) enterococcal strains known as vancomycin-resistant enterococci (VRE), currently constitutes a serious health problem in medical (human and veterinary) practices [ 73 ].…”

Selective Modification of Streptozotocin at the C3 Position to Improve Its Bioactivity as Antibiotic and Reduce Its Cytotoxicity towards Insulin-Producing β Cells

“…In the same vein it is obvious that not only epimerization and hydroxy group removal are possible but also conversion of the keto function into other functional groups and handles. Of the prepared analogues, keto-STZ (2) showed the highest antimicrobial activity and largest delay in bacterial growth, albeit significantly lower than parent STZ (1). Moreover, the toxicity to β cells was similarly largest for keto-STZ (2), limiting the applicability of this compound as an antibiotic.…”

“…Derivatization may overcome the existing resistance towards the antibiotic, can reduce its toxicity, and may even result in analogues that inhibit bacterial growth via a new mode of action. The effectiveness of this approach has been illustrated by the synthesis of derivatives of vancomycin, a potent inhibitor of bacterial cell wall synthesis, that overcome vancomycin-resistant enterococci infections [1]. Major efforts have been directed towards the (semi) synthesis of analogues of carbohydrate-based antibiotics, and in particular aminoglycosides [2,3].…”

Bacterial pathogens: threat or treat (a review on bioactive natural products from bacterial pathogens)

“…Nevertheless, modications of the complex vancomycin antibiotic have been achieved by several groups to produce potent analogues with less propensity to antibiotic resistance. 354 Lead optimisation of the odilorhabdin scaffold was also achieved and identied NOSO-502 as a clinical candidate for carbapenemresistant Enterobacteriaceae. 128 Several other metabolites that possess potent in vitro activity can be chemically-modied to increase in vivo efficacy and further enhance pharmacokinetic properties without diminishing activity such as bottromycin, althiomycin, caryoynencin, nocardithiocin, lugdunin, nematophin, holomycin, and reutericyclin.…”