Koul Vimarishi, Sharma Akshi, Kumari Diksha, Jamwal Vishwani, Palmo Tashi, Singh Kuljit
Infectious Diseases Division, CSIR- Indian Institute of Integrative Medicine, Jammu, 180001, India.
Department of Biological Sciences, Birla Institute of Technology and Sciences (BITS), Pilani campus, Pilani, Rajasthan, 333031, India.
Arch Microbiol. 2024 Dec 26;207(1):18. doi: 10.1007/s00203-024-04205-y.
Klebsiella pneumoniae is a leading cause of anti-microbial resistance in healthcare-associated infections that have posed a severe threat to neonatal and wider community. The escalating crises of antibiotic resistance have compelled researchers to explore an innovative arsenal beginning from natural resources to chemical modifications in order to overcome the ever-increasing resistance issues. The present review highlights the drug discovery efforts with a special focus on cutting-edge strategies in the hunt for potential drug candidates against MDR/XDR Klebsiella pneumoniae. Nature's bounty constituting plant extracts, essential oils, fungal extracts, etc. holds promising anti-bacterial potential especially when combined with existing antibiotics. Further, enhancing these natural products with synthetic moieties has improved their effectiveness, creating a bridge between the natural and synthetic world. Conversely, the synthetically modified novel scaffolds have been also designed to meticulously target specific sites. Furthermore, we have also elaborated various emerging strategies for broad-spectrum infections caused by K. pneumoniae, which include anti-microbial peptides, nanotechnology, drug repurposing, bacteriophage, photodynamic, and multidrug therapies. This review further addresses the challenges confronted by the research community and the future way forward in the field of drug discovery against multi-resistant bacterial infections.
肺炎克雷伯菌是医疗保健相关感染中抗菌药物耐药性的主要原因,对新生儿及更广泛的社区构成了严重威胁。抗生素耐药性危机不断升级,迫使研究人员探索从自然资源到化学修饰的创新武器库,以克服日益严重的耐药性问题。本综述重点介绍了药物发现方面的努力,特别关注寻找针对多重耐药/广泛耐药肺炎克雷伯菌潜在候选药物的前沿策略。大自然的馈赠,包括植物提取物、精油、真菌提取物等,具有可观的抗菌潜力,尤其是与现有抗生素联合使用时。此外,用合成部分增强这些天然产物提高了它们的有效性,在天然和合成世界之间架起了一座桥梁。相反,也设计了经过合成修饰的新型支架,以精确靶向特定部位。此外,我们还阐述了针对肺炎克雷伯菌引起的广谱感染的各种新兴策略,包括抗菌肽、纳米技术、药物再利用、噬菌体、光动力和多药疗法。本综述进一步探讨了研究界面临的挑战以及抗多重耐药细菌感染药物发现领域的未来发展方向。