Targeting plasmid-encoded proteins that contain immunoglobulin-like domains to combat antimicrobial resistance

Area of Science:

• Microbiology
• Immunology
• Molecular Biology

Background:

• Antimicrobial resistance (AMR) is a global health crisis.
• Bacterial plasmids are key drivers of AMR transmission.
• Identifying novel AMR targets is critical.

Purpose of the Study:

• To investigate bacterial surface proteins encoded by IncHI plasmids as potential AMR targets.
• To assess the immunogenicity and protective efficacy of these proteins.
• To develop targeted interventions against AMR plasmid transfer.

Main Methods:

• Identification of IncHI plasmid-encoded surface proteins with immunoglobulin-like domains.
• Immunization of mice with identified antigens and challenge with AMR *Salmonella*.
• Generation and characterization of nanobodies targeting these surface proteins.
• Assessment of nanobody efficacy in inhibiting plasmid conjugation.

Main Results:

• The identified surface proteins are antigenic and elicit protective immunity in mice against AMR *Salmonella* infection.
• Nanobodies targeting these proteins effectively inhibit IncHI plasmid conjugative transfer.
• These proteins are conserved across different plasmid groups (IncA/C, IncP2), suggesting broad applicability.

Conclusions:

• Bacterial surface proteins encoded by AMR plasmids represent a promising new strategy for combating AMR.
• Targeting these conserved antigens offers a broad-spectrum approach against diverse AMR-harboring bacteria.
• Nanobody-based interventions can disrupt AMR transmission by inhibiting plasmid transfer.