Project description:Plasmids are extrachromosomal genetic elements commonly found in bacteria. Plasmids are known to fuel bacterial evolution through horizontal gene transfer (HGT), but recent analyses indicate that they can also promote intragenomic adaptations. However, the role of plasmids as catalysts of bacterial evolution beyond HGT remains poorly explored. In this study, we investigate the impact of a widespread conjugative plasmid, pOXA-48, on the evolution of various multidrug-resistant clinical enterobacteria. Combining experimental and within-patient evolution analyses, we unveil that plasmid pOXA-48 promotes bacterial evolution through the transposition of plasmid-encoded IS1 elements. Specifically, IS1-mediated gene inactivations expedite the adaptation rate of clinical strains in vitro and foster within-patient adaptation in the gut. We decipher the mechanism underlying the plasmid-mediated surge in IS1 transposition, revealing a negative feedback loop regulated by the genomic copy number of IS1. Given the overrepresentation of IS elements in bacterial plasmids, our findings propose that plasmid-mediated IS transposition represents a crucial mechanism for swift bacterial adaptation.
Project description:The rapid pace of evolution in bacteria is widely attributed to the promiscuous horizontal transfer and recombination of protein-coding genes. However, it is not known whether the same forces also drive the evolution of non-coding regulatory regions. Here we demonstrate that regulatory region can M-bM-^@M-^XswitchM-bM-^@M-^Y between non-homologous alternatives and that such switching is ubiquitous, occurring across the bacterial domain. We show that such regulatory switching strongly impacts promoter architecture and expression divergence. We further show that regulatory transfer facilitates rapid phenotypic diversification of a human pathogen. This regulatory mobility enables bacterial genes to access a vast pool of potential regulatory elements, facilitating efficient exploration of the regulatory landscape. Examination of 2 E. coli strains in 2 conditions
Project description:Plasmid fitness is directed by two orthogonal processes—vertical transfer through cell division and horizontal transfer through conjugation. When considered individually, improvements in either mode of transfer can promote how well a plasmid spreads and persists. Together, however, the metabolic cost of conjugation could create a tradeoff that constrains plasmid evolution. Here we present evidence for the presence, consequences, and molecular basis of a conjugation-growth tradeoff across 40 plasmids derived from clinical E. coli pathogens. We discover that most plasmids operate below a conjugation efficiency threshold for major growth effects, indicating strong natural selection for vertical transfer. Below this threshold, E. coli demonstrates a remarkable growth tolerance to over four orders of magnitude change in conjugation efficiency. This tolerance fades as nutrients become scarce and horizontal transfer attracts a greater share of host resources. Our results provide insight into evolutionary constraints directing plasmid fitness and strategies to combat the spread of antibiotic resistance.
Project description:The rapid pace of evolution in bacteria is widely attributed to the promiscuous horizontal transfer and recombination of protein-coding genes. However, it is not known whether the same forces also drive the evolution of non-coding regulatory regions. Here we demonstrate that regulatory region can ‘switch’ between non-homologous alternatives and that such switching is ubiquitous, occurring across the bacterial domain. We show that such regulatory switching strongly impacts promoter architecture and expression divergence. We further show that regulatory transfer facilitates rapid phenotypic diversification of a human pathogen. This regulatory mobility enables bacterial genes to access a vast pool of potential regulatory elements, facilitating efficient exploration of the regulatory landscape.