Ammendola Serena, Secli Valerio, Pacello Francesca, Mastropasqua Maria Chiara, Romão Mariana A, Gomes Cláudio M, Battistoni Andrea
Department of Biology, Università of Rome ''Tor Vergata'', Via della Ricerca Scientifica, 00133 Rome, Italy.
Biosystems and Integrative Sciences Institute, Faculdade de Ciências, Universidade de Lisboa, Lisbon, Portugal.
FEMS Microbiol Lett. 2022 Aug 16;369(1). doi: 10.1093/femsle/fnac071.
Pseudomonas aeruginosa is known to exhibit considerable resistance to the antimicrobial activity of the metal-sequestering protein calprotectin (CP). In this study, we demonstrate that although CP induces zinc deficiency in P. aeruginosa, a strain unable to import zinc through the two most important metal acquisition systems, namely ZnuABC and ZrmABCD, maintains significant growth capacity in the presence of high concentrations of CP. Furthermore, we have shown that nicotianamine, a molecule structurally similar to the metallophore pseudopaline, can favor the acquisition of the metal even in the presence of CP. To gain insights into the mechanisms through which metallophores can promote zinc acquisition, we analyzed the effect of nicotianamine on the activity of the metallo-β-lactamase VIM-1. Our data suggest that metallophores released by bacteria in response to zinc deficiency can extract the protein-bound metal. The ability to interfere with the binding of metals to proteins, as well as favoring the acquisition of zinc, may contribute to increasing the resistance of P. aeruginosa to the antimicrobial action of CP.
已知铜绿假单胞菌对金属螯合蛋白钙卫蛋白（CP）的抗菌活性表现出相当大的抗性。在本研究中，我们证明，尽管CP会导致铜绿假单胞菌出现锌缺乏，但一株无法通过两个最重要的金属获取系统（即ZnuABC和ZrmABCD）导入锌的菌株，在高浓度CP存在的情况下仍保持显著的生长能力。此外，我们还表明，烟酰胺是一种在结构上与金属载体假巴马亭相似的分子，即使在CP存在的情况下，它也能促进金属的获取。为了深入了解金属载体促进锌获取的机制，我们分析了烟酰胺对金属β-内酰胺酶VIM-1活性的影响。我们的数据表明，细菌在锌缺乏时释放的金属载体可以提取与蛋白质结合的金属。干扰金属与蛋白质结合的能力以及促进锌的获取，可能有助于增加铜绿假单胞菌对CP抗菌作用的抗性。
