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鲍曼不动杆菌 OmpA 样孔蛋白:细菌生理学、抗生素耐药性和毒力的功能特征。

Acinetobacter baumannii OmpA-like porins: functional characterization of bacterial physiology, antibiotic-resistance, and virulence.

机构信息

Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.

Research Laboratories, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

出版信息

Commun Biol. 2024 Aug 6;7(1):948. doi: 10.1038/s42003-024-06645-0.

Abstract

Acinetobacter baumannii is a critical opportunistic pathogen associated with nosocomial infections. The high rates of antibiotic-resistance acquisition make most antibiotics ineffective. Thus, new medical countermeasures are urgently needed. Outer membrane proteins (OMPs) are prime candidates for developing novel drug targets and antibacterial strategies. However, there are substantial gaps in our knowledge of A. baumannii OMPs. This study reports the impact of OmpA-like protein on bacterial physiology and virulence in A. baumannii strain AB5075. We found that PsaB (ABUW_0505) negatively correlates to stress tolerance, while ArfA (ABUW_2730) significantly affects bacterial stiffness, cell shape, and cell envelope thickness. Furthermore, we expand our knowledge on YiaD (ABUW_3045), demonstrating structural and virulence roles of this porin, in addition to meropenem resistance. This study provides solid foundations for understanding how uncharacterized OMPs contribute to A. baumannii's physiological and pathological processes, aiding the development of innovative therapeutic strategies against A. baumannii infections.

摘要

鲍曼不动杆菌是一种与医院感染相关的重要机会性病原体。其对抗生素的高耐药率使得大多数抗生素无效。因此,迫切需要新的医疗对策。外膜蛋白(OMPs)是开发新型药物靶点和抗菌策略的首选候选物。然而,我们对鲍曼不动杆菌 OMPs 的了解还存在很大的差距。本研究报告了 OmpA 样蛋白对鲍曼不动杆菌 AB5075 株细菌生理和毒力的影响。我们发现 PsaB(ABUW_0505)与应激耐受性呈负相关,而 ArfA(ABUW_2730)显著影响细菌的刚性、细胞形状和细胞包膜厚度。此外,我们扩展了对 YiaD(ABUW_3045)的认识,除了对美罗培南的耐药性外,还证明了这种孔蛋白在结构和毒力方面的作用。本研究为理解未表征的 OMPs 如何促进鲍曼不动杆菌的生理和病理过程提供了坚实的基础,有助于开发针对鲍曼不动杆菌感染的创新治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0a0/11303520/d15c6c02cc9a/42003_2024_6645_Fig1_HTML.jpg

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