Reprogrammed SimCells for antimicrobial therapy

Area of Science:

• Synthetic Biology
• Microbiology
• Biotechnology

Background:

• Antimicrobial resistance (AMR) poses a significant global health threat.
• Existing treatments face challenges in specificity and efficacy against resistant pathogens.

Purpose of the Study:

• To develop a novel platform for targeted pathogen elimination using engineered simple cells (SimCells) and mini-SimCells.
• To engineer SimCells and mini-SimCells with nanobodies for specific bacterial antigen recognition.

Main Methods:

• Development of chromosome-free, nonreplicating SimCells and mini-SimCells.
• Surface display of nanobodies for targeted binding to bacterial antigens (e.g., OmpA in E. coli).
• Implementation of two antimicrobial mechanisms: type VI secretion system (T6SS) for effector injection and salicylate hydroxylase for H2O2 production.

Main Results:

• Engineered SimCells and mini-SimCells demonstrated high specificity and efficiency in eliminating target E. coli.
• Mini-SimCells achieved a 10^3-fold reduction of targeted bacteria in mixed communities with minimal impact on non-target species.
• Reprogrammed mini-SimCells targeting multidrug-resistant E. coli ST131 showed over 97% elimination efficiency within 48 hours.

Conclusions:

• The modular SimCell and mini-SimCell platform offers a highly specific and efficient approach to combating AMR pathogens.
• This adaptable technology presents a versatile solution for targeted elimination of diverse bacterial threats.
• The study highlights the potential of engineered simple cells as a next-generation antimicrobial strategy.