Effect of unsymmetrical oligo-phenylene-ethynylene OPE3 against multidrug-resistant bacteria in vitro and in vivo

Abstract

The rapid proliferation of multidrug-resistant (MDR) bacterial infections has posed the serious health threats. Photodynamic therapy is considered one of the most promising therapeutic strategies for combating bacterial resistance. In the present study, we synthesized an unsymmetrical oligo-p-phenylene ethynylene (OPE), namely OPE3, and investigated its antimicrobial activity against gram-negative and gram-positive MDR bacteria in vitro and in vivo. The results showed that OPE3 had marked antibacterial activity against MDR bacteria under light irradiation conditions. OPE3 exerted a slightly greater effect on gram-positive bacteria than gram-negative bacteria. Biofilm assay results showed that OPE3 could not inhibit biofilm formation at sub-minimum inhibitory concentrations (MICs), whereas a significant decrease in preformed biofilms was observed when they were treated with OPE3 at concentrations ≥2 × MIC. OPE3 had no hemolytic activity or cytotoxicity in mammalian cells at low concentrations. In the mouse model of burn infection caused by Pseudomonas aeruginosa and Staphylococcus aureus, the treatment of infected wounds with OPE3 resulted in a significant dose-dependent reduction in the bacterial load and caused smaller skin lesions. In addition, the levels of the inflammatory cytokines TNF-α and IL-6 in the serum were also significantly reduced. The present study results indicate that OPE3 may serve as a potent antimicrobial molecule for the treatment of MDR bacterial infections.

Keywords:

• Oligo-p-phenylene ethynylenes;
• Multidrug resistance;
• Antimicrobial activity;
• Biofilm;
• Toxicity

Conflict of interest

The authors report no conflict of interest.

Additional information

Funding

This work was supported by National Key Research and Development Plan of China [Number 2017YFC1200400].

Notes on contributors

Qian Yuan

Qian Yuan is an assistant researcher. Her research interests concentrate on the interaction of pathogenic bacteria with host cells.

Yu Wang is a pharmacist. She studied the new nano-preparations in the treatment of clinical anti-infection.

Pu Yao is a pharmacist. Her research interests concentrate on pharmacokinetics and pharmacodynamics study.

Jun Lv is an assistant researcher. He studied the anti-inflammatory and immunopharmacology of traditional Chinese medicine.

Qianmei Wang is a researcher of organic chemistry. She is mainly responsible for the synthesis of nanomaterials and exploring the role in anti-tumor therapy.

Fengjun Sun is a clinical pharmacist and associate professor. His research interests concentrate on molecular characteristics and infection prevention of multidrug-resistant bacteria.

Wei Feng is a microbiological technician. Her research interests concentrate on bacterial resistance and pathogenic mechanism.