Hyperbranched Polylysine Exhibits a Collaborative Enhancement of the Antibiotic Capacity to Kill Gram-Negative Pathogens.

Yuxin Gong, Qing Peng, Yu Qiao, Dandan Tian, Yuwei Zhang, Xiaoyan Xiong, Mengxin He, Xiaoqing Xu, Bo Shi
Author Information
  1. Yuxin Gong: Feed Research Institute, Chinese Academy of Agricultural Sciences, No. 12 South Zhongguancun Street, Beijing 100081, China.
  2. Qing Peng: Feed Research Institute, Chinese Academy of Agricultural Sciences, No. 12 South Zhongguancun Street, Beijing 100081, China.
  3. Yu Qiao: Feed Research Institute, Chinese Academy of Agricultural Sciences, No. 12 South Zhongguancun Street, Beijing 100081, China.
  4. Dandan Tian: Feed Research Institute, Chinese Academy of Agricultural Sciences, No. 12 South Zhongguancun Street, Beijing 100081, China.
  5. Yuwei Zhang: Institute of Agro-Products Preservation and Processing Technology, Tianjin Academy of Agricultural Sciences, Tianjin 300380, China.
  6. Xiaoyan Xiong: Feed Research Institute, Chinese Academy of Agricultural Sciences, No. 12 South Zhongguancun Street, Beijing 100081, China.
  7. Mengxin He: Feed Research Institute, Chinese Academy of Agricultural Sciences, No. 12 South Zhongguancun Street, Beijing 100081, China.
  8. Xiaoqing Xu: Feed Research Institute, Chinese Academy of Agricultural Sciences, No. 12 South Zhongguancun Street, Beijing 100081, China. ORCID
  9. Bo Shi: Feed Research Institute, Chinese Academy of Agricultural Sciences, No. 12 South Zhongguancun Street, Beijing 100081, China.

Abstract

In recent years, traditional antibiotic efficacy outcomes have rapidly diminished due to the advent of drug resistance, and the dose limitation value has increased due to the severe side effect of globalized healthcare. Therefore, novel strategies are required to resensitize resistant pathogens to antibiotics existing in the field and prevent the emergence of drug resistance. In this study, cationic hyperbranched polylysine (HBPL-6) was synthesized using the one-pot polymerization method. HBPL-6 exhibited excellent non-cytotoxicity and bio-solubility properties. The present study also showed that HBPL-6 altered the outer membrane (OM) integrity of O157:H7, , and by improving their permeability levels. When administered at a safe dosage, HBPL-6 enhanced the accumulation of rifampicin (RIF) and erythromycin (ERY) in bacteria to restore the efficacy of the antibiotics used. Moreover, the combination of HBPL-6 with colistin (COL) reduced the antibiotic dosage, which was helpful in preventing further drug-resistance outcomes. Therefore, this research provides a new strategy for reducing the dosage of drugs used to combat Gram-negative (G) bacteria through their synergistic effects.

Keywords

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Grants

  1. 1610382023018/Basal Research Fund of Feed Research Institute, Chinese Academy of Agricultural Sciences
  2. 6232039/Beijing Natural Science Foundation
  3. 32072773/National Natural Science Foundation of China

Word Cloud

Created with Highcharts 10.0.0HBPL-6dosageantibioticefficacyoutcomesduedrugresistanceThereforeantibioticsstudyhyperbranchedpolylysinebacteriausedsynergisticrecentyearstraditionalrapidlydiminishedadventdoselimitationvalueincreasedseveresideeffectglobalizedhealthcarenovelstrategiesrequiredresensitizeresistantpathogensexistingfieldpreventemergencecationicsynthesizedusingone-potpolymerizationmethodexhibitedexcellentnon-cytotoxicitybio-solubilitypropertiespresentalsoshowedalteredoutermembraneOMintegrityO157:H7improvingpermeabilitylevelsadministeredsafeenhancedaccumulationrifampicinRIFerythromycinERYrestoreMoreovercombinationcolistinCOLreducedhelpfulpreventingdrug-resistanceresearchprovidesnewstrategyreducingdrugscombatGram-negativeGeffectsHyperbranchedPolylysineExhibitsCollaborativeEnhancementAntibioticCapacityKillGram-NegativePathogensadjuvantspermeabilizationantibacterialTHERAPY

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