Conjugative plasmid-encoded toxin–antitoxin system PrpT/PrpA directly controls plasmid copy number

Songwei Ni, Baiyuan Li, Kaihao Tang, Jianyun Yao, Thomas K. Wood, Pengxia Wang, Xiaoxue Wang

Research output: Contribution to journalArticlepeer-review

Abstract

Toxin–antitoxin (TA) loci were initially identified on conjugative plasmids, and one function of plasmid-encoded TA systems is to stabilize plasmids or increase plasmid competition via postsegregational killing. Here, we discovered that the type II TA system, Pseudoalteromonas rubra plasmid toxin–antitoxin PrpT/PrpA, on a low-copy-number conjugative plasmid, directly controls plasmid replication. Toxin PrpT resembles ParE of plasmid RK2 while antitoxin PrpA (PF03693) shares no similarity with previously characterized antitoxins. Surprisingly, deleting this prpA-prpT operon from the plasmid does not result in plasmid segregational loss, but greatly increases plasmid copy number. Mechanistically, the antitoxin PrpA functions as a negative regulator of plasmid replication, by binding to the iterons in the plasmid origin that inhibits the binding of the replication initiator to the iterons. We also demonstrated that PrpA is produced at a higher level than PrpT to prevent the plasmid from overreplicating, while partial or complete degradation of labile PrpA derepresses plasmid replication. Importantly, the PrpT/PrpA TA system is conserved and is widespread on many conjugative plasmids. Altogether, we discovered a function of a plasmid-encoded TA system that provides new insights into the physiological significance of TA systems.

Original languageEnglish (US)
Article numbere2011577118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number4
DOIs
StatePublished - Jan 26 2021

All Science Journal Classification (ASJC) codes

  • General

Fingerprint Dive into the research topics of 'Conjugative plasmid-encoded toxin–antitoxin system PrpT/PrpA directly controls plasmid copy number'. Together they form a unique fingerprint.

Cite this