Das Theerthankar, Das Biswanath, Young Brandon Clark, Aldilla Vina, Sabir Shekh, Almohaywi Basmah, Willcox Mark, Manefield Mike, Kumar Naresh
Infection Immunity and Inflammation, Charles Perkins Centre, School of Medical Science, The University of Sydney, Sydney, NSW, Australia.
Sydney Institute for Infectious Diseases, School of Medical Science, The University of Sydney, Sydney, NSW, Australia.
Front Microbiol. 2023 Jul 13;14:1166607. doi: 10.3389/fmicb.2023.1166607. eCollection 2023.
The production of pyocyanin by increases its virulence, fitness and biofilm formation. Pyocyanin is also a redox molecule and we hypothesize that ascorbic acid being an antioxidant will interact with pyocyanin. The main objective of this study was to investigate the potential interaction of ascorbic acid with pyocyanin, and also to investigate the impact of ascorbic acid in combination with Furanone-30 on quorum sensing and biofilm formation of . When incubated with ascorbic acid, hyperchromic and hypsochromic shifts in pyocyanin absorbance peaks at 385 nm and 695 nm were observed. In the presence of dehydroascorbic acid and citric acid, these shifts were absent, indicating that the intrinsic antioxidant property of ascorbic acid was probably essential in binding to pyocyanin. NMR spectroscopy showed shifts in H NMR pyocyanin peaks between 8.2 to 5.8 ppm when incubated in the presence of ascorbic acid. Density Functional Theory (DFT) supported potential interactions between the -CHOH or -OH moieties of ascorbic acid with the -C=O moiety of pyocyanin. The pyocyanin-ascorbic acid complex impaired pyocyanin binding to DNA. Ascorbic acid combined with furanone-30 elevated quorum-sensing inhibition in , which was directly associated with significantly reduced virulence, adhesion, aggregation and biofilm formation and enhanced antibiotic-mediated bacterial killing. This study demonstrated that the antioxidant ascorbic acid directly binds to pyocyanin, modulates its structure and results in disruption of biofilm formation and associated tolerance to antibiotics.
绿脓菌素的产生会增加其毒力、适应性和生物膜形成能力。绿脓菌素也是一种氧化还原分子，我们推测作为抗氧化剂的抗坏血酸会与绿脓菌素相互作用。本研究的主要目的是研究抗坏血酸与绿脓菌素之间的潜在相互作用，以及抗坏血酸与呋喃酮 - 30联合使用对群体感应和生物膜形成的影响。当与抗坏血酸一起孵育时，观察到绿脓菌素在385 nm和695 nm处吸光度峰出现增色和减色位移。在脱氢抗坏血酸和柠檬酸存在的情况下，这些位移不存在，表明抗坏血酸的固有抗氧化特性可能是与绿脓菌素结合的关键。核磁共振光谱显示，当在抗坏血酸存在下孵育时，绿脓菌素的氢核磁共振峰在8.2至5.8 ppm之间发生位移。密度泛函理论（DFT）支持抗坏血酸的 -CHOH或 -OH基团与绿脓菌素的 -C=O基团之间的潜在相互作用。绿脓菌素 - 抗坏血酸复合物会损害绿脓菌素与DNA的结合。抗坏血酸与呋喃酮 - 30联合使用可提高群体感应抑制作用，这与显著降低毒力、黏附、聚集和生物膜形成以及增强抗生素介导的细菌杀伤直接相关。本研究表明，抗氧化剂抗坏血酸直接与绿脓菌素结合，调节其结构，并导致生物膜形成和相关抗生素耐受性的破坏。
