Battle against Vancomycin-Resistant Bacteria: Recent Developments in Chemical Strategies

Abstract

Vancomycin, a natural glycopeptide antibiotic, was used as the antibiotic of last resort for the treatment of multidrug-resistant Gram-positive bacterial infections. However, almost 30 years after its use, resistance to vancomycin was first reported in 1986 in France. This became a major health concern, and alternative treatment strategies were urgently needed. New classes of molecules, including semisynthetic antibacterial compounds and newer generations of the previously used antibiotics, were developed. Semisynthetic derivatives of vancomycin with enhanced binding affinity, membrane disruption ability, and lipid binding properties have exhibited promising results against both Gram-positive and Gram-negative bacteria. Various successful approaches developed to overcome the acquired resistance in Gram-positive bacteria, intrinsic resistance in Gram-negative bacteria, and other forms of noninherited resistance to vancomycin have been discussed in this Perspective.

Ligands and Receptors with Broad Binding Capabilities Have Common Structural Characteristics: An Antibiotic Design Perspective

“…beta-lactam antibiotics, fluoroquinolones, (or target substrates rather than enzymes e.g. vancomycin 10 ), while resistance emerges much more quickly for antibiotics that target only a single protein (e.g. sulfonamides, trimetophrim), and such drugs are used mostly in combination with other drugs 7,11 .…”

Amphiphilic Cationic Macromolecules Highly Effective Against Multi-Drug Resistant Gram-Positive Bacteria and Fungi With No Detectable Resistance

“…In this direction, numerous AMP mimicking membrane active agents has been developed by various groups all over the world. Most of the cases, the potency of such membrane active molecules was investigated against a broad spectra of pathogenic bacteria (Dhanda et al, 2019;Ghosh et al, 2019;Gupta V. K. et al, 2019). Antifungal efficacy was documented for very few amphiphilic polymers such as poly β-lactam and peptidopolysaccharides (Li et al, 2012;Liu et al, 2015).…”

Indole/isatin‐containing hybrids as potential antibacterial agents

“…[ 1,2 ] Antibiotics play indispensable roles in the treatment of bacterial infections, but the frequent and inappropriate application of antibiotics contributes to the fast spread of antibiotic resistance, which results in the reduced effectiveness of empiric antimicrobial treatment. [ 3–6 ] Antibiotic resistance has been considered as an alarming concern in Europe (59%), followed by Southeast Asia (18%), Western Pacific (12%), the Americas (6%), and Africa (6%), and over 700,000 deaths occur annually worldwide due to antibiotic resistance. [ 7,8 ] Thus, drug‐resistant bacteria have already posed a serious threat to human health, and it is imperative to deliver potent and novel antibacterial drug candidates.…”