Translational demand is not a major source of plasmid-associated fitness costs

• Type of Material: Article
• Authors: Jerónimo Rodríguez-Beltrán, Ramón y Cajal University Hospital; Ricardo León-Sampedro, Ramón y Cajal University Hospital; Paula Ramiro-Martínez, Ramón y Cajal University Hospital; Carmen De La Vega, Ramón y Cajal University Hospital; Fernando Baquero, Ramón y Cajal University Hospital; Bruce Levin, Emory University; Álvaro San Millán, Ramón y Cajal University Hospital
• Language: English
• Date: 2022-01-01
• Publisher: Emory University Libraries
• Publication Version: Final Published Version
• Copyright Statement: © 2021 The Authors
• Final Published Version (URL): http://dx.doi.org/10.1098/rstb.2020.0463
• Title of Journal or Parent Work: Philosophical Transactions of the Royal Society B: Biological Sciences
• Volume: 377
• Issue: 1842
• Start Page: 20200463
• End Page: 20200463
• Grant/Funding Information: This work was supported by the European Research Council under the European Union's Horizon 2020 research and innovation programme (ERC grant agreement no. 757440-PLASREVOLUTION) and by the Instituto de Salud Carlos III (co-funded by European Development Regional Fund ‘a way to achieve Europe’) grant no. PI19/00749. J.R.-B. acknowledges financial support by a Miguel Servet contract from ISCIII (grant no. CP20/00154), co-funded by ESF, ‘Investing in your future’. B.R.L.'s work is funded by US National Institutes of General Medical Sciences, grant no. R35 GM 136407. F.B.'s work is funded by the Project ST131TS from H2020 JPIAMR Programme of the EU, InGEMICS-CM, funded by Comunidad de Madrid (Spain) and European Structural and Investment Funds, CIBER in Epidemiology and Public Health, CIBERESP; grant no. CB06/02/0053, 2013–2016 and co-funded by Instituto de Salud Carlos III and the European Regional Development Fund (ERDF, ‘A way to achieve Europe’).
• Keywords: Plasmids; codon usage; horizontal gene transfer; Gene Transfer, Horizontal; ribosome; translational demand; Drug Resistance, Microbial; Bacteria; plasmid; fitness cost
• Research Categories: Biology, Microbiology; Biology, Genetics

Abstract

Plasmids are key drivers of bacterial evolution because they are crucial agents for the horizontal transfer of adaptive traits, such as antibiotic resistance. Most plasmids entail a metabolic burden that reduces the fitness of their host if there is no selection for plasmid-encoded genes. It has been hypothesized that the translational demand imposed by plasmid-encoded genes is a major mechanism driving the fitness cost of plasmids. Plasmid-encoded genes typically present a different codon usage from host chromosomal genes. As a consequence, the translation of plasmid-encoded genes might sequestrate ribosomes on plasmid transcripts, overwhelming the translation machinery of the cell. However, the pervasiveness and origins of the translation-derived costs of plasmids are yet to be assessed. Here, we systematically altered translation efficiency in the host cell to disentangle the fitness effects produced by six natural antibiotic resistance plasmids. We show that limiting translation efficiency either by reducing the number of available ribosomes or their processivity does not increase plasmid costs. Overall, our results suggest that ribosomal paucity is not a major contributor to plasmid fitness costs. This article is part of the theme issue 'The secret lives of microbial mobile genetic elements'.