Abstract
Plasmids play a major role in bacterial evolution and rapid adaptation by facilitating the horizontal transfer of diverse genes. Understanding how plasmids are transferred and maintained in bacterial populations is important, especially given the increasing plasmid-mediated spread of antibiotic-resistance genes to human pathogens. We investigated why broad-host range plasmid pBP136, originally isolated from clinical samples of
quickly became extinct in laboratory
populations. We found that the inactivation of a previously uncharacterized plasmid gene,
, drastically improved long-term maintenance of the plasmid in
. Loss of this single gene was associated with decreased transcription of numerous genes in the plasmid
,
and
regulons, as well as changes in many chromosomal genes primarily related to metabolism. This change in transcriptome is likely initiated by Upf31 interacting with one of these major plasmid regulators, KorB. Expression of
not only negatively affected the persistence of a pBP136
deletion mutant, but also of the closely related archetype IncPβ plasmid R751, which is stable in
and natively encodes an internally truncated
allele. This suggests that whereas the
allele in pBP136 might advantageously modulate gene expression in its original host,
, the same function can have harmful effects in
. Thus, using multiple hosts to study the effects of knockouts in broad-host-range plasmid genes of unknown function may reveal unexpected mechanisms that determine the fate of that plasmid in bacterial communities.