Rampant Parasexuality Evolves in a Hospital Pathogen during Antibiotic Selection

Area of Science:

• Microbiology
• Genetics
• Evolutionary Biology

Background:

• Horizontal gene transfer (HGT) is a major driver of antibiotic resistance dissemination among bacteria.
• The conjugative transposon Tn916 facilitates tetracycline resistance (tetM) and is found in diverse pathogens.
• Understanding adaptive mechanisms of resistance is crucial for combating clinical threats.

Purpose of the Study:

• To investigate adaptive evolution leading to tigecycline resistance in Enterococcus faecalis.
• To identify genetic mechanisms conferring resistance and their impact on HGT.
• To predict the emergence of resistance in clinical settings.

Main Methods:

• Experimental evolution of Enterococcus faecalis under tigecycline selection.
• Allelic frequency measurements to track resistance and HGT.
• Identification of specific mutations conferring resistance.

Main Results:

• Antibiotic selection rapidly fixed adaptive alleles that enhanced TetM expression and Tn916 transfer.
• Conjugation rates increased over 1,000-fold upon selection for resistance.
• Tigecycline selected for a mutation in the ribosomal S10 protein, conferring resistance.
• Observed mutations simultaneously conferred antibiotic resistance and constitutive conjugal transfer of resistance alleles.

Conclusions:

• Antibiotic use can directly drive the proliferation of resistance by selecting for mutations that enhance HGT.
• This study demonstrates a novel mechanism where resistance acquisition promotes further spread.
• The findings highlight the potential for rapid evolution of antibiotic resistance in pathogens.