scholarly journals Antibiotic adjuvants to rescue Pseudomonas aeruginosa from tetracycline antibiotics resistance

2020 ◽  
Vol 18 ◽  
Author(s):  
Azza Troudi ◽  
Hana Douafer ◽  
Jean-Michel Bolla ◽  
Naouel Klibi ◽  
Jean Michel Brunel

Introduction: An attractive antibiotic-adjuvant strategy consisting in the design and synthesis of polyaminoisoprenyl molecules able to restore antibiotic activity of tetracycline antibiotics against resistant Pseudomonas aeruginosa bacterial strains has been developed. Methods: These chemo-sensitizers are readily prepared from geraniol and farnesol in an efficient two steps synthesis with good to moderate yields varying from 38 to 64% and leading to a significant decrease of antibiotic resistance. Results: Thus, the influence of the nature of the tetracycline antibiotic used as well as the structure of the polyaminoisoprenyl derivatives involved on the outcome of the antibiotic-adjuvant combination against P. aeruginosa resistance to tetracyclines were investigated. Conclusion: Additionally, our data suggested that their mechanism of action is closely associated with the increase of the outer-membrane permeability.

2018 ◽  
Vol 54 (99) ◽  
pp. 13929-13932 ◽  
Author(s):  
Max Purro ◽  
Jing Qiao ◽  
Zhi Liu ◽  
Morgan Ashcraft ◽  
May P. Xiong

The outer membrane ofPseudomonas aeruginosafunctions primarily as a permeability barrier and imparts a broad spectrum of intrinsic antibiotic resistance.


mSystems ◽  
2020 ◽  
Vol 5 (3) ◽  
Author(s):  
Daniel Bouzo ◽  
Nural N. Cokcetin ◽  
Liping Li ◽  
Giulia Ballerin ◽  
Amy L. Bottomley ◽  
...  

ABSTRACT Manuka honey has broad-spectrum antimicrobial activity, and unlike traditional antibiotics, resistance to its killing effects has not been reported. However, its mechanism of action remains unclear. Here, we investigated the mechanism of action of manuka honey and its key antibacterial components using a transcriptomic approach in a model organism, Pseudomonas aeruginosa. We show that no single component of honey can account for its total antimicrobial action, and that honey affects the expression of genes in the SOS response, oxidative damage, and quorum sensing. Manuka honey uniquely affects genes involved in the explosive cell lysis process and in maintaining the electron transport chain, causing protons to leak across membranes and collapsing the proton motive force, and it induces membrane depolarization and permeabilization in P. aeruginosa. These data indicate that the activity of manuka honey comes from multiple mechanisms of action that do not engender bacterial resistance. IMPORTANCE The threat of antimicrobial resistance to human health has prompted interest in complex, natural products with antimicrobial activity. Honey has been an effective topical wound treatment throughout history, predominantly due to its broad-spectrum antimicrobial activity. Unlike traditional antibiotics, honey-resistant bacteria have not been reported; however, honey remains underutilized in the clinic in part due to a lack of understanding of its mechanism of action. Here, we demonstrate that honey affects multiple processes in bacteria, and this is not explained by its major antibacterial components. Honey also uniquely affects bacterial membranes, and this can be exploited for combination therapy with antibiotics that are otherwise ineffective on their own. We argue that honey should be included as part of the current array of wound treatments due to its effective antibacterial activity that does not promote resistance in bacteria.


2006 ◽  
Vol 52 (5) ◽  
pp. 295-301 ◽  
Author(s):  
Christopher M. Runyan ◽  
John C. Carmen ◽  
Benjamin L. Beckstead ◽  
Jared L. Nelson ◽  
Richard A. Robison ◽  
...  

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