Antimicrobial Research Laboratory, New Chemistry Unit, Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Jakkur, Bengaluru 560064, Karnataka, India.
Biochemistry and Molecular Biology Program, Departments of Chemistry and Biology, College of Arts and Science, Boston University, Boston, Massachusetts 02215, United States.
ACS Infect Dis. 2022 Jan 14;8(1):1-28. doi: 10.1021/acsinfecdis.1c00367. Epub 2021 Dec 8.
Glycopeptides, a class of cell wall biosynthesis inhibitors, have been the antibiotics of choice against drug-resistant Gram-positive bacterial infections. Their unique mechanism of action involving binding to the substrate of cell wall biosynthesis and substantial longevity in clinics makes this class of antibiotics an attractive choice for drug repurposing and reprofiling. However, resistance to glycopeptides has been observed due to alterations in the substrate, cell wall thickening, or both. The emergence of glycopeptide resistance has resulted in the development of synthetic and semisynthetic glycopeptide analogues to target acquired resistance. Recent findings demonstrate that these derivatives, along with some of the FDA approved glycopeptides have been shown to have antimicrobial activity against Gram-negative bacteria, Mycobacteria, and viruses thus expanding their spectrum of activity across the microbial kingdom. Additional mechanisms of action and identification of novel targets have proven to be critical in broadening the spectrum of activity of glycopeptides. This review focuses on the applications of glycopeptides beyond their traditional target group of Gram-positive bacteria. This will aid in making the scientific community aware about the nontraditional activity profiles of glycopeptides, identify the existing loopholes, and further explore this antibiotic class as a potential broad-spectrum antimicrobial agent.
糖肽类，一类细胞壁生物合成抑制剂，一直是治疗耐药革兰氏阳性菌感染的首选抗生素。它们独特的作用机制涉及与细胞壁生物合成的底物结合，以及在临床上的长期存在，使这类抗生素成为药物重新利用和重新定位的有吸引力的选择。然而，由于底物的改变、细胞壁增厚或两者兼而有之，已经观察到对糖肽类的耐药性。糖肽类耐药性的出现导致了合成和半合成糖肽类似物的开发，以针对获得性耐药。最近的研究结果表明，这些衍生物以及一些已获 FDA 批准的糖肽类药物已被证明对革兰氏阴性菌、分枝杆菌和病毒具有抗菌活性，从而扩大了它们在微生物界的作用范围。额外的作用机制和新靶点的鉴定已被证明在扩大糖肽类的作用谱方面至关重要。本综述重点介绍了糖肽类在其传统的革兰氏阳性菌靶群之外的应用。这将有助于科学界了解糖肽类的非传统活性特征，发现现有漏洞，并进一步探索这类抗生素作为一种潜在的广谱抗菌药物。
