Synergistic effect of two antimicrobial peptides, Nisin and P10 with conventional antibiotics against extensively drug-resistant Acinetobacter baumannii and colistin-resistant Pseudomonas aeruginosa isolates,Microbial Pathogenesis

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Synergistic effect of two antimicrobial peptides, Nisin and P10 with conventional antibiotics against extensively drug-resistant Acinetobacter baumannii and colistin-resistant Pseudomonas aeruginosa isolates
Microbial Pathogenesis ( IF 3.3 ) Pub Date : 2020-12-17 , DOI: 10.1016/j.micpath.2020.104700
Abolfazl Jahangiri ₁ , Alireza Neshani ₂ , Seyed Ali Mirhosseini ₁ , Kiarash Ghazvini ₃ , Hosna Zare ₄ , Hamid Sedighian ₁

Affiliation

Background

Infections caused by drug-resistant strains of Acinetobacter baumannii and Pseudomonas aeruginosa are now a global problem that requires the immediate development of new antimicrobial drugs. Combination therapy and using antimicrobial peptides are two strategies with high potential to solve this issue. By these strategies, this study aimed to determine the antimicrobial effect of Nisin and P10 antimicrobial peptides on extensively drug-resistant Acinetobacter baumannii and colistin-resistant Pseudomonas aeruginosa isolates, and investigate the most effective combination of an antimicrobial peptide with an antibiotic.

Material and methods

This study was performed on five resistant clinical isolates and one standard strain for each kind of bacterium. First, the minimum inhibitory concentrations of two antimicrobial peptides (Nisin and P10) and five common antibiotics for the treatment of Gram-negative bacteria (ceftazidime, tobramycin, ciprofloxacin, doripenem, and colistin) was determined using Scanner-Assisted Colorimetric MIC Method. Then, the combination effect of P10+Nisin, P10+antibiotics, Nisin + antibiotics was investigated using checkerboard method.

Results

The MIC value of Nisin and P10 against studied pathogens were 64–256 and 8–32 μg/ml, respectively. P10+Nisin combination showed synergistic effect against standard strains and additive effect against drug-resistant clinical isolates. It was also found that the combination effect of P10+ceftazidim, P10+doripenem, and Nisin + colistin was synergistic in most cases. Nisin + tobramycin combination showed synergistic effect in exposure to standard strains, while the synergy is strain-dependent against drug-resistant clinical isolates.

Conclusion

In conclusion, the synergism of Nisin + colistin and P10+ceftazidime/doripenem could be of great therapeutic value as antimicrobial drugs against infections caused by colistin-resistant P.aeruginosa and XDR A. baumannii.

中文翻译：

Nisin和P10这两种抗菌肽与常规抗生素对广泛耐药的鲍曼不动杆菌和大肠菌素耐药的铜绿假单胞菌分离株的协同作用

背景

由鲍曼不动杆菌和铜绿假单胞菌的耐药菌株引起的感染现在是一个全球性问题，需要立即开发新的抗菌药物。联合疗法和使用抗菌肽是解决这一问题的两种潜在方法。通过这些策略，本研究旨在确定Nisin和P10抗菌肽对广泛耐药的鲍曼不动杆菌和大肠菌素耐药性铜绿假单胞菌分离物的抗菌效果，并研究抗菌肽与抗生素的最有效组合。

材料与方法

这项研究是针对每种细菌对五种耐药临床分离株和一种标准菌株进行的。首先，使用扫描仪辅助比色MIC方法确定了两种抗菌肽（乳酸链球菌素和P10）和五种常见的革兰氏阴性细菌（头孢他啶，妥布霉素，环丙沙星，多利培南和粘菌素）的最小抑菌浓度。然后，采用棋盘法研究了P10 +乳链菌肽，P10 +抗生素，乳链菌肽+抗生素的联合作用。

结果

Nisin和P10对研究的病原体的MIC值分别为64–256和8–32μg/ ml。P10 + Nisin组合物对标准菌株具有协同作用，对耐药性临床分离株具有累加作用。还发现，在大多数情况下，P10 +头孢他啶，P10 +多洛培南和乳链菌肽+粘菌素的组合作用是协同的。Nisin +妥布霉素组合在暴露于标准菌株中显示出协同作用，而协同作用则对耐药的临床分离株具有菌株依赖性。