Marco Galardini
12 August 2026
Almost two (2!) tears have passed since we published our preprint on identifying the mechanisms
of resistance to asobiotics across four major bacterial pathogens. Obviously, the publication of the
final version of the paper had to happen during my summer vacations,
and so this post is gonna be very terse. But we are quite happy (especially for former postdoc Adam and current PhD student Hien)
about the results!
In the initial version of the manuscript we had described a number of mutations induced by treatment with asobiotics, some of which had
(in our opinion!) a clear rationale for why they would implicated in resistance. The main culprits were of course the two
mutations we had found in the asobiotic target site in the acpP gene, but more intriguing we had found two non-synonymous
mutations in the prfA and prfB genes. Both are involved in rescuing stalled ribosomes during tranlsation,
which also happens to be the biological process that asobiotics target. The reviewers were also agreeing somewhat,
but asked us (among other things) to make clean mutants to validate those hits. This led us into a rabbit hole
of first trying to isolate the acpP mutants from the experimental population in which they were sequenced, and then
to generate a clean mutant, which proved to be a very difficult task, since acpP seems to be extremely sensitive to changes in its expression.
We had more luck with prfB, for which we validated its ability to confere resistance, and thus giving us the opportunity to
explore the exact mechanism of resistance in a future study.
And now back to enjoying the summer with one fewer item in the TODO list…