Cooperative antibiotic resistance facilitates horizontal gene transfer

Area of Science:

• Microbiology
• Evolutionary Biology
• Genetics

Background:

• Antibiotic resistance, particularly beta-lactam resistance, is a global health crisis driven by horizontal gene transfer of beta-lactamases.
• Beta-lactamases protect not only producing bacteria but also neighboring sensitive cells, a cooperative trait whose impact on plasmid dynamics is unclear.

Purpose of the Study:

• To investigate how cooperative beta-lactamase activity influences plasmid transmission and maintenance.
• To compare the fitness and transfer efficiency of cooperative (KPC-2 encoding) versus non-cooperative plasmids under varying antibiotic conditions.

Main Methods:

• Experimental evolution and conjugation assays were used to study plasmid dynamics.
• Comparative analysis of plasmid-encoded KPC-2 beta-lactamase expression and extracellular activity versus chromosomal expression.
• Competition experiments between strains with cooperative and non-cooperative plasmids in the presence and absence of beta-lactam antibiotics.

Main Results:

• Plasmid-encoded KPC-2 beta-lactamase showed higher expression and extracellular activity, leading to enhanced rescue of sensitive non-producer cells.
• Cooperative beta-lactamase activity facilitated efficient plasmid transfer to rescued non-producers, expanding the recipient pool and enabling transfer to new genotypes.
• Cooperative plasmids were outcompeted by non-cooperative ones without antibiotics but were strongly favored in the presence of beta-lactams, while plasmid-free cells showed higher fitness than plasmid-carrying cells.

Conclusions:

• Cooperative antibiotic resistance mechanisms, like beta-lactamase activity, significantly enhance the fitness and horizontal transfer of mobile genetic elements such as conjugative plasmids.
• This cooperative trait plays a critical role in the spread and maintenance of antibiotic resistance genes within bacterial populations.
• Understanding these cooperative dynamics is essential for developing strategies to control the spread of antimicrobial resistance.