Scribano Daniela, Pasqua Martina, Limongi Dolores, Nencioni Lucia, Palamara Anna Teresa, Ambrosi Cecilia
Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185, Rome, Italy.
Department of Biology and Biotechnologies "Charles Darwin", Institute Pasteur Italia, Sapienza University of Rome, 00185, Rome, Italy.
Biol Res. 2025 Jan 10;58(1):2. doi: 10.1186/s40659-025-00584-8.
Acinetobacter baumannii poses a significant threat globally, causing infections primarily in healthcare settings, with high mortality rates. Its adaptability to antibiotic resistance and tolerance to various stresses, including reactive oxygen species (ROS), contribute to its persistence in healthcare environments. Previous evidence suggested that the periplasmic heat shock protein, HslJ-like protein (ABUW_2868), could be involved in oxidative stress defense in A. baumannii. In this study, we demonstrate the pivotal function of HslJ as the first line of defense against oxidative damage induced by hydrogen peroxide (HO).
An isogenic site-specific hslJ mutant of A. baumannii AB5075 was used to evaluate its sensitivity to HO, survival rate in human macrophages, biofilm, cell surface hydrophobicity, and motility. Additionally, the hslJ expression profile was measured under stress conditions and its OxyR-dependent regulation was assessed both in vitro and in a heterologous host.
Herein, we report that HslJ is under the positive regulatory control of OxyR, which upregulates its expression in response to imipenem (IMP) and HO, thereby underscoring its importance in A. baumannii survival strategy. In addition, our findings revealed that the hslJ mutant displayed abrogated surface-associated motility accompanied by increased cell surface hydrophobicity (CSH), indicating also a role in maintaining cell membrane properties.
This comprehensive understanding of HslJ multifaceted role not only enriches our knowledge of A. baumannii stress response mechanisms but also provides valuable insights for developing targeted strategies to eradicate this deadly resilient pathogen in healthcare settings.
鲍曼不动杆菌在全球构成重大威胁，主要在医疗环境中引起感染，死亡率很高。它对抗生素耐药性的适应性以及对包括活性氧（ROS）在内的各种应激的耐受性，使其在医疗环境中得以持续存在。先前的证据表明，周质热休克蛋白，即类HslJ蛋白（ABUW_2868），可能参与鲍曼不动杆菌的氧化应激防御。在本研究中，我们证明了HslJ作为抵御过氧化氢（HO）诱导的氧化损伤的第一道防线的关键作用。
使用鲍曼不动杆菌AB5075的同基因位点特异性hslJ突变体来评估其对HO的敏感性、在人巨噬细胞中的存活率、生物膜、细胞表面疏水性和运动性。此外，在应激条件下测量hslJ的表达谱，并在体外和异源宿主中评估其OxyR依赖性调控。
在此，我们报告HslJ受OxyR的正调控，OxyR在亚胺培南（IMP）和HO刺激下上调其表达，从而突出了其在鲍曼不动杆菌生存策略中的重要性。此外，我们的研究结果表明，hslJ突变体表现出表面相关运动能力丧失，同时细胞表面疏水性（CSH）增加，这也表明其在维持细胞膜特性方面发挥作用。
对HslJ多方面作用的全面理解不仅丰富了我们对鲍曼不动杆菌应激反应机制的认识，也为制定有针对性的策略以根除医疗环境中这种致命的耐药病原体提供了有价值的见解。
