Plasmid Costs Explain Plasmid Maintenance, Irrespective of the Nature of Compensatory Mutations

Antibiotics (Basel). 2023 May 1;12(5):841. doi: 10.3390/antibiotics12050841.

Abstract

Conjugative plasmids often carry virulence and antibiotic-resistant genes. Therefore, understanding the behavior of these extra-chromosomal DNA elements gives insights into their spread. Bacteria frequently replicate slower after plasmids' entry, an observation inconsistent with the plasmids' ubiquity in nature. Several hypotheses explain the maintenance of plasmids among bacterial communities. However, the numerous combinations of bacterial species and strains, plasmids, and environments claim a robust elucidatory mechanism of plasmid maintenance. Previous works have shown that donor cells already adapted to the plasmid may use the plasmid as a 'weapon' to compete with non-adapted plasmid-free cells. Computer simulations corroborated this hypothesis with a wide range of parameters. Here we show that donor cells benefit from harboring conjugative plasmids even if compensatory mutations in transconjugant cells occur in the plasmid, not on chromosomes. The advantage's leading causes are as follows: mutations take time to appear, many plasmids remain costly, and re-transfer of mutated plasmids usually occurs in sites distant to the original donors, implying little competition between these cells. Research in previous decades cautioned against uncritical acceptance of the hypothesis that resistance cost helps to preserve antibiotics' effectiveness. This work gives a new twist to this conclusion by showing that costs help antibiotic-resistant bacteria to compete with plasmid-free cells even if compensatory mutations appear in plasmids.

Keywords: adaptation; antibiotic resistance; computer simulations; conjugation; conjugative plasmids; fitness cost.

Grants and funding

João S. Rebelo and Célia P. F. Domingues acknowledge FCT-Fundação para a Ciência e a Tecnologia, IP for their fellowships (PhD grants SFRH/BD/04631/2021 and UI/BD/153078/2022, respectively). FCT also supports cE3c by contract UIDP/00329/2020.