What causes plasmid incompatibility?

Plasmids are incompatible when they share replicons with identical Rep protein specificity or controlling factors. Plasmids sharing identical replicons are incompatible because they compete for the same cellular replication control mechanisms. Typically, plasmids have a system that regulates replication negatively, involving either iterons or antisense RNAs. These components prevent excessive replication when plasmid numbers are high but allow it when numbers drop too low. Antisense RNAs hinder replication either indirectly by impeding the translation of replication proteins. They can also directly bind to the replication origin. As plasmid numbers rise, the increased presence of these antisense RNAs inhibit further replication.

Incompatibility may also arise from competition between similar or closely related partitioning systems. The similarity in partitioning can lead to competition for crucial proteins (NTPase and centromere-like region binding protein) involved in plasmid segregation during cell division. Insufficient quantities of these proteins result in unorganized plasmid distribution among daughter cells, ultimately causing plasmid loss.