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

• 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
• Journal Title: Philosophical Transactions of the Royal Society B: Biological Sciences
• Volume: Volume 377, Number 1842
• Publisher: (publisher) | 2022-01-01, Pages 20200463-20200463
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1098/rstb.2020.0463
• Keywords: codon usage; fitness cost; horizontal gene transfer; plasmid; ribosome; translational demand; Bacteria; Drug Resistance, Microbial; Gene Transfer, Horizontal; Plasmids

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'.