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Published on: July 7, 2020
Fluoroamphiphilic polymers exterminate multidrug-resistant Gram-negative ESKAPE pathogens while attenuating drug
Qian Zhou1, Kunpeng Li1, Kun Wang1
1Frontiers Science Center for Flexible Electronics, (FSCFE), Xi'an Institute of Flexible Electronics (IFE) and Xi'an Institute of Biomedical Materials & Engineering (IBME), Ningbo Institute, Northwestern Polytechnical University, 127 West Youyi Road, Xi'an 710072, China.
Abstract:
ESKAPE pathogens are a panel of most recalcitrant bacteria that could "escape" the treatment of antibiotics and exhibit high incidence of drug resistance. The emergence of multidrug-resistant (MDR) ESKAPE pathogens (particularly Gram-negative bacteria) accounts for high risk of mortality and increased resource utilization in health care. Worse still, there has been no new class of antibiotics approved for exterminating the Gram-negative bacteria for more than 50 years. Therefore, it is urgent to develop novel antibacterial agents with low resistance and potent killing efficacy against Gram-negative ESKAPE pathogens. Herein, we present a class of fluoropolymers by mimicking the amphiphilicity of cationic antimicrobial peptides. Our optimal fluoroamphiphilic polymer (PD45HF5) displayed selective antimicrobial ability for all MDR Gram-negative ESAKPE pathogens, low resistance, high in vitro cell selectivity, and in vivo curative efficacy. These findings implied great potential of fluoroamphiphilic cationic polymers as promising antibacterial agents against MDR Gram-negative ESKAPE bacteria and alleviating antibiotic resistance.
Insights
New fluoroamphiphilic polymers show potent activity against multidrug-resistant (MDR) ESKAPE pathogens. This breakthrough offers a promising alternative to combat Gram-negative bacterial infections and address the urgent need for novel antibiotics.
Area of Science:
- Polymer Chemistry
- Antimicrobial Research
- Infectious Diseases
Background:
- ESKAPE pathogens are a major cause of hospital-acquired infections.
- Multidrug-resistant (MDR) Gram-negative bacteria, including ESKAPE pathogens, pose a significant threat due to limited treatment options.
- There has been a lack of new antibiotic classes for Gram-negative bacteria in over 50 years.
Purpose of the Study:
- To develop novel antibacterial agents effective against MDR Gram-negative ESKAPE pathogens.
- To explore fluoroamphiphilic polymers as a potential solution to antibiotic resistance.
- To evaluate the efficacy and safety of a new class of polymers against resistant bacteria.
Main Methods:
- Synthesis of fluoroamphiphilic polymers mimicking cationic antimicrobial peptides.
- Testing the optimal polymer (PD45HF5) against a panel of MDR Gram-negative ESKAPE pathogens.
- Assessing antimicrobial activity, resistance development, in vitro cell selectivity, and in vivo efficacy.
Main Results:
- The optimal fluoroamphiphilic polymer (PD45HF5) demonstrated selective antimicrobial activity against all tested MDR Gram-negative ESKAPE pathogens.
- The polymer exhibited low potential for resistance development.
- High in vitro cell selectivity and significant in vivo curative efficacy were observed.
Conclusions:
- Fluoroamphiphilic cationic polymers represent a promising new class of antibacterial agents.
- These polymers show potential for combating MDR Gram-negative ESKAPE bacteria.
- This approach could help alleviate the global crisis of antibiotic resistance.
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