PAβN dihydrochloride (MC-207,110 dihydrochloride) is a peptide mimetic compound that is a broad-spectrum bacterial efflux pump inhibitor (EPI)[1]. PAβN dihydrochloride is the first inhibitor of the resistance nodule cell differentiation (RND) family of efflux pumps in Gram-negative bacteria[2]. PAβN dihydrochloride reduces the resistance of Pseudomonas aeruginosa to fluoroquinolones[3]. PAβN dihydrochloride can cause a 2- to 2048-fold decrease in the MIC of antimicrobial agents known to be substrates of the CmeABC pump in all Campylobacter strains[4]. PAβN dihydrochloride can be used to evaluate the efficacy of new EPI candidates[5].
In vitro, treatment of Salmonella typhimurium cells with PAβN dihydrochloride (32μM) inhibited efflux activity, increased the accumulation of ethidium (Et+) and tetraphenylphosphine (TPP+) in cells, and stimulated Et+ fluorescence[6].
References:
[1] Y Mahmood H, Jamshidi S, Mark Sutton J, et al. Current advances in developing inhibitors of bacterial multidrug efflux pumps[J]. Current medicinal chemistry, 2016, 23(10): 1062-1081.
[2] Compagne N, Vieira Da Cruz A, Müller R T, et al. Update on the discovery of efflux pump inhibitors against critical priority Gram-negative bacteria[J]. Antibiotics, 2023, 12(1): 180.
[3] Rahbar M, Hamidi-Farahani R, Asgari A, et al. Expression of RND efflux pumps mediated antibiotic resistance in Pseudomonas aeruginosa clinical strains[J]. Microbial Pathogenesis, 2021, 153: 104789.
[4] Martinez A, Lin J. Effect of an efflux pump inhibitor on the function of the multidrug efflux pump CmeABC and antimicrobial resistance in Campylobacter[J]. Foodbourne Pathogens & Disease, 2006, 3(4): 393-402.
[5] Blankson G A. Structure-activity studies on bacterial efflux inhibitors[M]. Rutgers The State University of New Jersey, School of Graduate Studies, 2016.
[6] Sakalauskaitė S, Mikalayeva V, Daugelavičius R. Ethidium binding to Salmonella enterica ser. Typhimurium Cells and Salmon sperm DNA[J]. Molecules, 2021, 26(11): 3386.
PAβN dihydrochloride (MC-207,110 dihydrochloride)是一种肽模拟化合物，是一种广谱细菌外排泵抑制剂（EPI）[1]。PAβN dihydrochloride是革兰氏阴性菌中耐药结节细胞分化家族（RND）外排泵的第一个抑制剂[2]。PAβN dihydrochloride降低铜绿假单胞菌对氟喹诺酮类药物的耐药性[3]。PAβN dihydrochloride能够导致所有弯曲杆菌菌株中已知为CmeABC泵底物的抗菌剂的MIC降低2至2048倍[4]。PAβN dihydrochloride能够用于评估新EPI候选物的效率[5]。
在体外，PAβN dihydrochloride（32μM）处理鼠伤寒沙门氏菌细胞，可抑制外排活性，增加细胞中乙锭（Et+）和四苯基磷（TPP+）的积累并刺激Et+荧光[6]。