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ESKAPE 病原体中激酶的治疗干预见解。

Insights into Kinases of ESKAPE Pathogens for Therapeutic Interventions.

机构信息

Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Canada.

Department of Biotechnology, Jaypee Institute of Information Technology, Sector-62, Noida, U.P., 201307, India.

出版信息

Cardiovasc Hematol Agents Med Chem. 2024;22(3):276-297. doi: 10.2174/0118715257267497231128093529.

Abstract

Multidrug-resistant ESKAPE pathogens are the leading cause of hospital-acquired infections across the globe, posing challenges for clinicians. Random genetic mutations and constant exposure to antibiotics in healthcare settings result in strains resistant to commonly used antibiotics, creating life-threatening conditions. If the magic of "antibiotics" is to be sustained, a new class of antimicrobials against novel targets is urgently needed. This necessitates understanding and identifying novel biochemical pathways and bacterial virulence factors that can be targeted for therapeutic interventions. Keeping in view the unambiguous role of the kinome in bacterial survival and virulence, this review provides a survey of effector bacterial kinases involved in evading host immune responses and drug resistance. The formation of biofilms is a critical feature associated with the pathogenesis and survival of ESKAPE organisms in the hostile host milieu. Hence, kinases involved in the biofilm pathway are also elucidated for clinical relevance. In addition, endeavors in the development of therapeutics against ESKAPE kinases are also summarized to provide direction to researchers pursuing the field.

摘要

耐多药 ESKAPE 病原体是全球医院获得性感染的主要原因,给临床医生带来了挑战。随机的基因突变和在医疗机构中持续接触抗生素导致了对常用抗生素产生耐药性的菌株,从而造成危及生命的情况。如果要维持“抗生素”的神奇效果,就迫切需要针对新靶点的新型抗菌药物。这就需要了解和确定可用于治疗干预的新型生化途径和细菌毒力因子。鉴于激酶组在细菌存活和毒力中的明确作用,本综述提供了对逃避宿主免疫反应和耐药性的细菌效应激酶的调查。生物膜的形成是与 ESKAPE 生物体在恶劣宿主环境中发病和存活相关的关键特征。因此,还阐明了与生物膜途径相关的激酶的临床相关性。此外,还总结了针对 ESKAPE 激酶的治疗药物开发方面的努力,为从事该领域的研究人员提供了方向。

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