Plasmid interference for curing antibiotic resistance plasmids in vivo

Area of Science:

• Microbiology
• Molecular Biology
• Genetics

Background:

• Antibiotic resistance is a growing global health threat, increasing mortality from common bacterial infections.
• Antibiotic resistance genes frequently spread via conjugative plasmids within and between bacterial species.
• Plasmids utilize incompatibility (Inc) and addiction systems to ensure their persistence within bacterial populations.

Purpose of the Study:

• To investigate the potential of exploiting plasmid incompatibility and addiction systems for antibiotic resistance eradication.
• To develop and test 'interference plasmids' capable of eliminating antibiotic resistance plasmids from bacteria.

Main Methods:

• Engineered conjugative plasmids ('interference plasmids') by removing toxin and antibiotic resistance genes from target plasmids.
• Tested the efficacy of interference plasmids in curing antibiotic resistance plasmids from Enterobacteriaceae in vitro.
• Evaluated the restoration of antibiotic susceptibility in vivo using a mouse gut model.

Main Results:

• Interference plasmids successfully and completely eradicated target antibiotic resistance plasmids from various Enterobacteriaceae strains in vitro.
• Treatment with interference plasmids restored antibiotic susceptibility in bacterial populations in a mouse gut model.
• Demonstrated the potential for safe and complete removal of antibiotic resistance.

Conclusions:

• Exploiting plasmid incompatibility and addiction systems offers a promising strategy for eradicating antibiotic resistance.
• This approach could be valuable for treating individuals at risk of sepsis and for bioremediation applications.
• Further research is warranted to explore the generalizability and applications of this method in diverse microbiomes.