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针对多药耐药鲍曼不动杆菌潜在抗生物膜靶点的治疗策略。

Therapeutic strategies against potential antibiofilm targets of multidrug-resistant Acinetobacter baumannii.

机构信息

Department of Biochemistry, Central University of Rajasthan, Ajmer, India.

出版信息

J Cell Physiol. 2022 Apr;237(4):2045-2063. doi: 10.1002/jcp.30683. Epub 2022 Jan 26.

Abstract

Acinetobacter baumannii is the causative agent of various hospital-acquired infections. Biofilm formation is one of the various antimicrobial resistance (AMR) strategies and is associated with high mortality and morbidity. Hence, it is essential to review the potential antibiofilm targets in A. baumannii and come up with different strategies to combat these potential targets. This review covers different pathways involved in the regulation of biofilm formation in A. baumannii like quorum sensing (QS), cyclic-di-GMP signaling, two-component system (TCS), outer-membrane protein (ompA), and biofilm-associated protein (BAP). A newly discovered mechanism of electrical signaling-mediated biofilm formation and contact-dependent biofilm modulation has also been discussed. As biofilm formation and its maintenance in A. baumannii is facilitated by these potential targets, the detailed study of these targets and pathways can bring light to different therapeutic strategies such as anti-biofilm peptides, natural and synthetic molecule inhibitors, QS molecule degrading enzymes, and other strategies. These strategies may help in suppressing the lethality of biofilm-mediated infections. Targeting essential proteins/targets which are crucial for biofilm formation and regulation may render new therapeutic strategies that can aid in combating biofilm, thus reducing the recalcitrant infections and morbidity associated with the biofilm of A. baumannii.

摘要

鲍曼不动杆菌是各种医院获得性感染的病原体。生物膜形成是多种抗菌药物耐药(AMR)策略之一,与高死亡率和高发病率有关。因此,有必要审查鲍曼不动杆菌中潜在的抗生物膜靶标,并制定不同的策略来对抗这些潜在的靶标。这篇综述涵盖了参与鲍曼不动杆菌生物膜形成调节的不同途径,如群体感应(QS)、环二鸟苷酸信号转导、双组分系统(TCS)、外膜蛋白(ompA)和生物膜相关蛋白(BAP)。还讨论了一种新发现的电信号介导生物膜形成和接触依赖性生物膜调节的机制。由于这些潜在的靶标促进了鲍曼不动杆菌生物膜的形成和维持,因此详细研究这些靶标和途径可以为不同的治疗策略带来启示,如抗生物膜肽、天然和合成分子抑制剂、QS 分子降解酶等。这些策略可能有助于抑制生物膜介导感染的致死性。针对对生物膜形成和调节至关重要的必需蛋白/靶标,可能会产生新的治疗策略,有助于对抗生物膜,从而减少与鲍曼不动杆菌生物膜相关的难治性感染和发病率。

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