Remotely Controllable Engineered Bacteria for Targeted Therapy of Pseudomonas aeruginosa Infection
Yanmei Gao1,2, Jingjing Wei3, Lu Pu4
1Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, No. 96, JinZhai Road, Baohe District, Hefei, Anhui 230026, P. R. China.
Abstract:
Pseudomonas aeruginosa (P. aeruginosa) infection has become an intractable problem worldwide due to the decreasing efficacy of the mainstay therapy, antibiotic treatment. Hence, exploring new drugs and therapies to address this issue is crucial. Here, we construct a chimeric pyocin (ChPy) to specifically kill P. aeruginosa and engineer a near-infrared (NIR) light-responsive strain to produce and deliver this drug. Our engineered bacterial strain can continuously produce ChPy in the absence of light and release it to kill P. aeruginosa via remotely and precisely controlled bacterial lysis induced by NIR light. We demonstrate that our engineered bacterial strain is effective in P. aeruginosa-infected wound therapy in the mouse model, as it eradicated PAO1 in mouse wounds and shortened the wound healing time. Our work presents a potentially spatiotemporal and noninvasively controlled therapeutic strategy of engineered bacteria for the targeted treatment of P. aeruginosa infections.
Insights
Researchers engineered a bacterial strain to produce a pyocin drug that specifically targets Pseudomonas aeruginosa infections. Near-infrared light controls drug release, showing effectiveness in mouse wound healing models.
Area of Science:
- Synthetic biology and antimicrobial therapy.
- Bacteriophage-derived proteins for targeted bacterial killing.
Background:
- Pseudomonas aeruginosa infections pose a significant global health challenge due to widespread antibiotic resistance.
- Current antibiotic treatments are becoming less effective, necessitating novel therapeutic approaches.
Purpose of the Study:
- To develop a novel therapeutic strategy for Pseudomonas aeruginosa infections.
- To engineer a bacterial strain capable of producing and delivering a targeted antimicrobial agent.
- To enable spatiotemporal and non-invasive control over drug delivery using near-infrared light.
Main Methods:
- Construction of a chimeric pyocin (ChPy) specifically targeting P. aeruginosa.
- Engineering of a bacterial strain to produce and release ChPy upon near-infrared (NIR) light stimulation.
- Evaluation of the engineered strain's efficacy in a P. aeruginosa-infected mouse wound model.
Main Results:
- The engineered bacterial strain successfully produced and delivered ChPy to kill P. aeruginosa.
- NIR light enabled precise, remote control over bacterial lysis and drug release.
- Treatment with the engineered strain eradicated PAO1 in mouse wounds and accelerated wound healing.
Conclusions:
- Engineered bacteria offer a promising platform for targeted antimicrobial drug delivery.
- NIR-inducible bacterial lysis provides a non-invasive method for controlling therapeutic agent release.
- This strategy demonstrates potential for effective treatment of P. aeruginosa wound infections.
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