Some bacteria can rapidly multiply genes useful for their survival, particularly under the effect of an antibiotic. A study describes a gene amplification mechanism that has been underestimated until now, capable of promoting rapid and reversible adaptation.
Gene amplification corresponds to the creation of several copies of the same DNA region. The more a gene is copied, the more the cell can produce the associated protein. This gain is sometimes temporary, but it can provide an immediate advantage in a hostile environment.
E. coli bacterium
Photo by Eric Erbe, digital colorization by Christopher Pooley
The researchers developed a computer tool named AmpliFinder. It detects, in short sequencing data, the junctions left when small mobile DNA fragments move or copy regions of the bacterial chromosome.
The team analyzed 10,347 isolates obtained during laboratory evolution experiments. The set included 9,696 samples of Escherichia coli and 651 of Acinetobacter baumannii. The researchers identified 113 new amplifications associated with these mobile elements.
The majority did not follow the expected classic pattern. In E. coli, 81 amplifications out of 106 were called noncanonical, compared with 25 classic forms. These atypical structures were often shorter and present in more copies, which can concentrate the advantage on a few specific genes.
In experiments conducted with antibiotics, these noncanonical amplifications more often contained resistance genes than chance would predict: an enrichment reaching 3.4 times the expected value.
An experiment with chloramphenicol made it possible to directly follow this process. A region containing the mdfA resistance gene went from one copy to more than 13 copies during adaptation. This increase could then decrease when the selection pressure changed.
AmpliFinder will now make it possible to search for these structures in other genomic collections, notably clinical and environmental isolates. Researchers will then be able to measure their real frequency and determine their contribution to resistances encountered outside the laboratory.