Abstract：
The purpose of this study was to evaluate the antimicrobial activity of indole-3-carbinol (I3C) with membrane-active agents, namely carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and ethylenediaminetetraacetic acid (EDTA) against multidrug-resistant (MDR) Gram-negative bacteria and bacterial persisters. The determination of minimal inhibitory concentration (MIC) showed that I3C was effective against Acinetobacter baumannii (3.13‒6.25 × 10-3 mol l-1), Klebsiella pneumoniae (8 × 10-3 mol l-1), Pseudomonas aeruginosa (6.25‒12.5 × 10-3 mol l-1), and Escherichia coli (6.25‒12.5 × 10-3 mol l-1). Our study demonstrated that EDTA synergistically enhanced the bactericidal activity of I3C against most MDR Gram-negative bacteria isolates and contributed to an 8- to 64-fold MIC reduction compared with that of I3C alone, yet CCCP only displayed synergy with I3C against P. aeruginosa and A. baumannii. The EDTA-I3C combination also significantly reduced the viable number of testing bacteria (P = 7.2E-05), effectively reduced bacterial persisters, and repressed bacterial growth compared with that the use of I3C alone. Our data demonstrate that use of EDTA as adjuvant molecules can effectively improve the antibacterial activity of I3C and may help to reduce the development of antimicrobial resistance.
摘要：
这项研究的目的是评估吲哚-3-甲醇（I3C）与膜活性剂的抗菌活性，即羰基氰化物3-氯苯腙（CCCP）和EDTA抗多药耐药（MDR）革兰氏阴性菌和细菌持久性。最小抑菌浓度(MIC)测定表明,I3C对鲍曼不动杆菌(3.13~6.25×10-3moll-1)有效,肺炎克雷伯菌（8×10-3moll-1），铜绿假单胞菌（6.25-12.5×10-3moll-1），和大肠杆菌（6.25~12.5×10-3moll-1）。我们的研究表明，EDTA协同增强了I3C对大多数MDR革兰氏阴性菌分离株的杀菌活性，与单独使用I3C相比，MIC降低了8到64倍。然而CCCP仅显示与I3C对铜绿假单胞菌和鲍曼不动杆菌的协同作用。EDTA-I3C组合也显著降低了检测细菌的活菌数(P=7.2E-05),有效减少细菌持久性，与单独使用I3C相比，抑制了细菌的生长。我们的数据表明，使用EDTA作为佐剂分子可以有效地提高I3C的抗菌活性，并可能有助于减少抗菌耐药性的发展。
