Abstract
Horizontal gene transfer (HGT) plays a key role in bacterial evolution, especially with respect to antibiotic resistance. Fitness costs associated with mobile genetic elements (MGEs) are thought to constrain HGT, but our understanding of these costs remains fragmentary, making it difficult to predict the success of HGT events. Here we use the interaction between P. aeruginosa and a costly plasmid (pNUK73) to investigate the molecular basis of the cost of HGT. Using RNA-Seq, we show that the acquisition of pNUK73 results in a profound alteration of the transcriptional profile of chromosomal genes. Mutations that inactivate two genes encoded on chromosomally integrated MGEs recover these fitness costs and transcriptional changes by decreasing the expression of the pNUK73 replication gene. Our study demonstrates that interactions between MGEs can compromise bacterial fitness via altered gene expression, and we argue that conflicts between mobile elements impose a general constraint on evolution by HGT.
Highlights
Horizontal gene transfer (HGT) plays a key role in bacterial evolution, especially with respect to antibiotic resistance
As a first approach in understanding the molecular basis of the cost produced by pNUK73 in PAO1, we used RNA-Seq to analyse the genome-wide transcriptional profiles of PAO1 and PAO1 carrying PNUK73 plasmid (PAO1/pNUK73)
One compensatory mutation was found in a putative helicase gene (PA1372 with premature stop codon at position 378, Fig. 1), while the other was in a putative kinase gene (PA4673.15 with premature stop codon at position 95, Fig. 1)
Summary
Horizontal gene transfer (HGT) plays a key role in bacterial evolution, especially with respect to antibiotic resistance. Using RNA-Seq, we examine changes in the global transcriptional profile of the PAO1 host as a consequence of carrying the pNUK73 plasmid We find that this plasmid produces a highly significant impact on the transcriptional profile of the host, including the induction of the SOS response via the expression of the plasmid replication protein gene rep. Our results in the PAO1/pNUK73 system suggest that the interference between horizontally acquired elements drives the cost of HGT We propose that this type of costly interactions between recently acquired MGE may be a general phenomenon in prokaryotes
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