Growth-stage-dependent regulation of conjugation

Plasmid conjugation is a driving force behind the spread of antibiotic resistance genes. While problematic for medical purposes, conjugation can be used for delivery of target genes in microbial communities, for example, for bioremediation. Physiological state of the host bacterial cell strongly affects the transfer of the prototypic F-plasmid of Escherichia coli, but it remains unclear whether such modulation is wide-spread. We tested a broad range of Enterobacteriaceae conjugative plasmids for their sensitivity to the growth stage of the donors and identified three distinct regulation types. As many of the domesticated conjugative plasmids have been considered de-regulated, we tested transfer of conjugative plasmids from clinical E. coli strains and found that they undergo growth-stage regulation, similar to the F plasmid. We identified that transcription regulation is behind the transfer modulation. The observed diversity of conjugation regulation can be used in engineering bacterial communities to spread and maintain genes of interest.