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Updated: May 5, 2026
High-throughput Identification of Bacteria Repellent Polymers for Medical Devices
Published on: November 5, 2016
Phosphate-containing polyethylene glycol polymers prevent lethal sepsis by multidrug-resistant pathogens
Alexander Zaborin1, Jennifer R Defazio, Matthew Kade
1University of Chicago, Chicago, Illinois, USA.
Abstract:
Antibiotic resistance among highly pathogenic strains of bacteria and fungi is a growing concern in the face of the ability to sustain life during critical illness with advancing medical interventions. The longer patients remain critically ill, the more likely they are to become colonized by multidrug-resistant (MDR) pathogens. The human gastrointestinal tract is the primary site of colonization of many MDR pathogens and is a major source of life-threatening infections due to these microorganisms. Eradication measures to sterilize the gut are difficult if not impossible and carry the risk of further antibiotic resistance. Here, we present a strategy to contain rather than eliminate MDR pathogens by using an agent that interferes with the ability of colonizing pathogens to express virulence in response to host-derived and local environmental factors. The antivirulence agent is a phosphorylated triblock high-molecular-weight polymer (here termed Pi-PEG 15-20) that exploits the known properties of phosphate (Pi) and polyethylene glycol 15-20 (PEG 15-20) to suppress microbial virulence and protect the integrity of the intestinal epithelium. The compound is nonmicrobiocidal and appears to be highly effective when tested both in vitro and in vivo. Structure functional analyses suggest that the hydrophobic bis-aromatic moiety at the polymer center is of particular importance to the biological function of Pi-PEG 15-20, beyond its phosphate content. Animal studies demonstrate that Pi-PEG prevents mortality in mice inoculated with multiple highly virulent pathogenic organisms from hospitalized patients in association with preservation of the core microbiome.
Insights
A novel polymer, Pi-PEG 15-20, contains multidrug-resistant (MDR) pathogens by suppressing virulence, not killing microbes. This strategy protects the gut microbiome and prevents mortality in animal models.
Area of Science:
- Microbiology
- Polymer Science
- Critical Care Medicine
Background:
- Antibiotic resistance in pathogenic bacteria and fungi is a growing global health concern.
- Multidrug-resistant (MDR) pathogens frequently colonize the gastrointestinal tract of critically ill patients, leading to life-threatening infections.
- Current gut sterilization methods are often ineffective and risk exacerbating antibiotic resistance.
Purpose of the Study:
- To introduce a novel strategy for managing MDR pathogens by containing them rather than eliminating them.
- To investigate the efficacy of a phosphorylated triblock high-molecular-weight polymer (Pi-PEG 15-20) as an antivirulence agent.
- To assess the compound's ability to suppress pathogen virulence and protect intestinal epithelial integrity.
Main Methods:
- Development and characterization of Pi-PEG 15-20, a polymer designed to interfere with pathogen virulence factor expression.
- In vitro and in vivo testing of Pi-PEG 15-20's efficacy against MDR pathogens.
- Structure-function analysis to identify key components of the polymer responsible for its biological activity.
- Animal studies using mice challenged with virulent pathogens to evaluate mortality and microbiome preservation.
Main Results:
- Pi-PEG 15-20 effectively suppresses the virulence of colonizing MDR pathogens without being microbiocidal.
- The compound demonstrates efficacy in both in vitro and in vivo experimental models.
- Structure-function studies highlight the importance of the polymer's hydrophobic bis-aromatic moiety for its biological activity.
- In vivo studies showed Pi-PEG 15-20 prevented mortality in mice infected with virulent pathogens and preserved the gut microbiome.
Conclusions:
- Pi-PEG 15-20 represents a promising antivirulence strategy for managing MDR pathogen colonization in critically ill patients.
- This non-microbiocidal approach offers a potential alternative to traditional antibiotics, mitigating the risk of further resistance.
- The preservation of the host microbiome alongside virulence suppression is a key advantage of this novel therapeutic agent.
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