An In Vitro Study on the Effects of Nisin on the Antibacterial Activities of 18 Antibiotics against Enterococcus faecalis

Zhongchun Tong,Lijia Huang,Yuejiao Zhang,Jinglei Ma,Luodan Zhang,Junqi Ling,Lynn E Hancock

doi:10.1371/journal.pone.0089209

Abstract

Enterococcus faecalis rank among the leading causes of nosocomial infections worldwide and possesses both intrinsic and acquired resistance to a variety of antibiotics. Development of new antibiotics is limited, and pathogens continually generate new antibiotic resistance. Many researchers aim to identify strategies to effectively kill this drug-resistant pathogen. Here, we evaluated the effect of the antimicrobial peptide nisin on the antibacterial activities of 18 antibiotics against E. faecalis. The MIC and MBC results showed that the antibacterial activities of 18 antibiotics against E. faecalis OG1RF, ATCC 29212, and strain E were significantly improved in the presence of 200 U/ml nisin. Statistically significant differences were observed between the results with and without 200 U/ml nisin at the same concentrations of penicillin or chloramphenicol (p<0.05). The checkerboard assay showed that the combination of nisin and penicillin or chloramphenicol had a synergetic effect against the three tested E. faecalis strains. The transmission electron microscope images showed that E. faecalis was not obviously destroyed by penicillin or chloramphenicol alone but was severely disrupted by either antibiotic in combination with nisin. Furthermore, assessing biofilms by a confocal laser scanning microscope showed that penicillin, ciprofloxacin, and chloramphenicol all showed stronger antibiofilm actions in combination with nisin than when these antibiotics were administered alone. Therefore, nisin can significantly improve the antibacterial and antibiofilm activities of many antibiotics, and certain antibiotics in combination with nisin have considerable potential for use as inhibitors of this drug-resistant pathogen.

Highlights

Antibiotics have saved the lives of millions of people, greatly improving human and animal health in the twentieth century.bacterial pathogens commonly develop resistance to many antibiotics due to the extensive use of these antibiotics for human and animal health
Penicillin, ampicillin, gentamicin, kanamycin, roxithromycin, sulfapyridine, streptomycin, vancomycin, chloramphenicol, cefuroxime, cephazolin, ceftriaxone, cefepime, metronidazole, ciprofloxacin, polymyxin, imipenem, and linezolid were prepared at the concentration of 4,096 mg/L
Of the 18 tested antibiotics, 3, 5, and 9 antibiotics did not result in detectable Minimum Bactericidal Concentration (MBC) against OG1RF, ATCC 29212, and strain E, respectively, and E. faecalis strains exhibited a high level of resistance to the antibiotics

Summary

Introduction

Antibiotics have saved the lives of millions of people, greatly improving human and animal health in the twentieth century. Bacterial pathogens commonly develop resistance to many antibiotics due to the extensive use of these antibiotics for human and animal health. Hundreds of thousands of deaths occur annually due to antibiotic treatment failures [1]. The routine approach to addressing this crisis is to develop novel antibiotics. Novel antibiotics are limited, and pathogens will gradually evolve resistance to these novel antibiotics [2]. Based on the inevitable trend towards bacterial resistance, it is necessary to explore new treatment strategies for effectively killing and eliminating bacterial pathogens. Limiting the evolution of bacterial resistance and using new and existing antibiotics may constitute a new strategy for antibacterial therapy

Methods

Results

Conclusion