Molecular gatekeepers in bacteria prevent the spread of antibiotic resistance

A new study finds that bacteria can actively block the transfer of beneficial genes to neighboring cells, using specialized proteins to specifically destroy shared DNA before it spreads. This challenges the long-held view that bacteria freely exchange genetic material and reveals a more competitive system in which microbes tightly control who gets access to valuable traits, an insight that could help scientists better understand and potentially limit the spread of antibiotic resistance.

A new study reveals that bacteria can actively limit the spread of antibiotic resistance genes, using a newly characterized mechanism that blocks DNA transfer between cells. The research, led by Prof. Sigal Ben-Yehuda and Prof. Ilan Rosenshine of Hebrew University-Hadassah Medical Center and published in Nature Microbiology, focuses on how bacteria exchange genetic material through tiny intercellular bridges known as nanotubes, a pathway the team previously identified as a mode of horizontal gene transfer.

These nanotubes allow bacteria to pass plasmids, small DNA molecules that often carry antibiotic resistance genes, directly from one cell to another. Unlike classical mechanisms such as transformation or conjugation, this nanotube-mediated exchange enables close, contact-dependent sharing of genetic traits in a bi-directional manner, allowing both the donor to deliver DNA or the recipient to actively acquire it.

The new study shows that this process is not unrestricted. The researchers discovered that a protein called YokF acts as a molecular “gatekeeper,” blocking specifically the transfer of plasmids through nanotubes. YokF functions as an enzyme that degrades DNA during transfer, effectively preventing neighboring bacteria from acquiring potentially beneficial traits.

This mechanism allows bacteria to keep valuable genes to themselves, giving them a competitive advantage in dense microbial communities. Importantly, the study demonstrates that this nanotube-based gene transfer, and its inhibition, plays a significant role in the spread of small plasmids, many of which carry antibiotic resistance. By limiting this transfer, YokF reduces how quickly these traits can move through bacterial populations.

Further analysis revealed that YokF-like proteins are widespread across many Gram-positive bacteria, suggesting that this is not an isolated phenomenon but a common strategy used to regulate gene flow.

The findings highlight a previously underappreciated layer of control in bacterial evolution. Microbes are not just sharing genes, they are actively managing their distribution. Understanding this process could open new avenues for tackling antibiotic resistance by targeting the mechanisms that enable or restrict the spread of resistance genes.