Viganor Livia, Galdino Anna Clara M, Nunes Ana Paula F, Santos Kátia R N, Branquinha Marta H, Devereux Michael, Kellett Andrew, McCann Malachy, Santos André L S
General Microbiology Department, Institute of Microbiology Paulo de Góes, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil The Inorganic Pharmaceutical and Biomimetic Research Centre, Focas Research Institute, Dublin Institute of Technology, Dublin, Ireland.
General Microbiology Department, Institute of Microbiology Paulo de Góes, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil Biochemistry Post-Graduation Programme, Chemistry Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
J Antimicrob Chemother. 2016 Jan;71(1):128-34. doi: 10.1093/jac/dkv292. Epub 2015 Sep 27.
The beneficial antimicrobial properties of 1,10-phenanthroline (phen)-based drugs, together with the imperative need to develop new chemotherapeutic options for prevention/treatment of infections caused by MDR Gram-negative bacteria, led us to evaluate the effects of phen, 1,10-phenanthroline-5,6-dione (phendione), [Ag(phendione)2]ClO4 and Cu(phendione)32·4H2O on planktonic- and biofilm-growing Pseudomonas aeruginosa.
Thirty-two non-duplicated Brazilian clinical isolates of P. aeruginosa with distinct genetic backgrounds were used in all experiments. The effect of test compounds on planktonic bacterial proliferation was determined as recommended by CLSI protocol. The effect on biofilm formation was evaluated by crystal violet incorporation (biomass determination) and XTT (viability assay). Mature biofilm disorganization was evidenced by staining with crystal violet.
Phen-based compounds presented anti-P. aeruginosa activity, but with different potencies concerning the geometric mean MIC: Cu(phendione)3 (7.76 μM) > Ag(phendione)2 (14.05 μM) > phendione (31.15 μM) > phen (579.28 μM). MICs of each compound were similar irrespective of whether the P. aeruginosa isolates were susceptible or resistant to classical antimicrobials (ceftazidime, meropenem and imipenem). The pretreatment of bacteria with phen, phendione and phendione's metal derivatives at 0.5 × MIC value inhibited biofilm formation, particularly the use of Cu(phendione)3 and Ag(phendione)2, which significantly reduced both biomass (48% and 44%, respectively) and viability (78% and 77%, respectively). The compounds studied also disrupted mature biofilm in a dose-dependent manner, especially Ag(phendione)2 and Cu(phendione)3 (IC50, 9.39 and 10.16 μM, respectively).
Coordination of phendione to Ag(+) and Cu(2+) represents a new promising group of anti-infective agents, which revealed a potent anti-P. aeruginosa action against both planktonic- and biofilm-growing cells.
1,10 - 菲咯啉（phen）类药物具有有益的抗菌特性，同时迫切需要开发新的化疗方案来预防/治疗由多重耐药革兰氏阴性菌引起的感染，这促使我们评估phen、1,10 - 菲咯啉 - 5,6 - 二酮（phendione）、[Ag(phendione)₂]ClO₄和Cu(phendione)₃₂·4H₂O对浮游生长和生物膜生长的铜绿假单胞菌的影响。
在所有实验中使用了32株具有不同遗传背景的非重复巴西临床分离铜绿假单胞菌。按照CLSI协议推荐的方法测定受试化合物对浮游细菌增殖的影响。通过结晶紫掺入法（生物量测定）和XTT法（活力测定）评估对生物膜形成的影响。用结晶紫染色证明成熟生物膜的解体。
基于phen的化合物呈现出抗铜绿假单胞菌活性，但就几何平均MIC而言效力不同：Cu(phendione)₃（7.76 μM）＞Ag(phendione)₂（14.05 μM）＞phendione（31.15 μM）＞phen（579.28 μM）。无论铜绿假单胞菌分离株对经典抗菌药物（头孢他啶、美罗培南和亚胺培南）敏感或耐药，每种化合物的MIC均相似。用phen、phendione及其金属衍生物以0.5×MIC值预处理细菌可抑制生物膜形成，特别是Cu(phendione)₃和Ag(phendione)₂的使用，它们分别显著降低了生物量（分别为48%和44%）和活力（分别为78%和77%）。所研究的化合物还以剂量依赖性方式破坏成熟生物膜，尤其是Ag(phendione)₂和Cu(phendione)₃（IC₅₀分别为9.39和10.16 μM）。
phendione与Ag(+)和Cu(2+)的配位代表了一类新的有前景的抗感染剂，其对浮游生长和生物膜生长的细胞均显示出强大的抗铜绿假单胞菌作用。
