Lab in Microbiology and Marine Biotechnology, Department of Biotechnology, School of Biological Sciences, Alagappa University, Karaikudi 630 003, India.
Lab in Microbiology and Marine Biotechnology, Department of Biotechnology, School of Biological Sciences, Alagappa University, Karaikudi 630 003, India; Department of Biotechnology, Vels Institute of Science, Technology & Advanced Studies (VISTAS), Chennai 600117, India.
Int J Biol Macromol. 2023 Jan 31;226:853-869. doi: 10.1016/j.ijbiomac.2022.12.045. Epub 2022 Dec 13.
Acinetobacter baumannii, a virulent uropathogen with widespread antibiotic resistance, has arisen as a critical scientific challenge, necessitating the development of innovative therapeutic agents. This is the first study reveal the proteomic changes in A. baumannii upon pyrogallol treatment for understanding the mechanisms using nano-LC-MS/MS-based quantitative proteomics and qPCR analysis. The obtained results found that pyrogallol treatment dramatically downregulated the expression level of several key proteins such as GroEL, DnaK, ClpB, SodB, KatE, Bap, CsuA/B, PgaA, PgaC, BfmR, OmpA, and SecA in A. baumannii, which are involved in chaperone-mediated oxidative stress responses, antioxidant defence system, biofilm formation, virulence enzyme production, bacterial adhesion, capsule formation, and antibiotic resistance. Accordingly, the pyrogallol dramatically enhanced the lifespan of A. baumannii-infected zebrafish by inhibiting bacterial colonization, demonstrating the anti-infective potential of pyrogallol against A. baumannii. Further, the histopathological results also demonstrated the disease protection efficacy of pyrogallol against the pathognomonic sign of A. baumannii infection. In addition, the pyrogallol treatment effectively improved the immune parameters such as serum myeloperoxidase activity, leukocyte respiratory burst activity, and serum lysozyme activity in zebrafish against A. baumannii infection. Based on the results, the present study strongly proposes pyrogallol as a promising therapeutic agent for treating A. baumannii infection.
鲍曼不动杆菌是一种具有广泛抗生素耐药性的毒力尿路病原体，已成为一个重大的科学挑战，需要开发创新的治疗药物。这是第一项研究，揭示了焦儿茶酚处理鲍曼不动杆菌时的蛋白质组变化，通过基于纳米 LC-MS/MS 的定量蛋白质组学和 qPCR 分析来了解其机制。获得的结果发现，焦儿茶酚处理显著下调了 GroEL、DnaK、ClpB、SodB、KatE、Bap、CsuA/B、PgaA、PgaC、BfmR、OmpA 和 SecA 等关键蛋白的表达水平，这些蛋白参与伴侣介导的氧化应激反应、抗氧化防御系统、生物膜形成、毒力酶产生、细菌黏附、荚膜形成和抗生素耐药性。因此，焦儿茶酚通过抑制细菌定植显著延长了感染鲍曼不动杆菌的斑马鱼的寿命，证明了焦儿茶酚对鲍曼不动杆菌的抗感染潜力。此外，组织病理学结果还证明了焦儿茶酚对鲍曼不动杆菌感染的特征性标志具有疾病保护作用。另外，焦儿茶酚处理有效改善了感染鲍曼不动杆菌的斑马鱼的免疫参数，如血清髓过氧化物酶活性、白细胞呼吸爆发活性和血清溶菌酶活性。基于这些结果，本研究强烈提出焦儿茶酚作为治疗鲍曼不动杆菌感染的有前途的治疗药物。
