Pangenome Analysis Reveals Novel Contact-Dependent Growth Inhibition System and Phenazine Biosynthesis Operons in Proteus mirabilis BL95 That Are Located in An Integrative and Conjugative Element

Proteus mirabilis is a leading cause of urinary tract infections and a common commensal of the gastrointestinal tract. Our recent study (JB) showed that P. mirabilis strain BL95 employs a novel contact-dependent killing system against enteric bacteria in the mouse gut and in vitro. To uncover the genetic determinants of this system, we performed whole-genome sequencing of BL95 and compared it with 98 complete genomes of P. mirabilis. BL95 carries 56 coding sequences (CDSs) not found in other P. mirabilis. Over half of these unique genes are located on a novel integrative conjugative element (ICE) named ICEPm2, inserted in tRNA-Phe and exclusive to BL95. ICEPm2 has integration, conjugation, and DNA replication modules nearly identical to ICEPm1 (common in P. mirabilis), but ICEPm2 of BL95 carries two unique operons for P. mirabilis—a phenazine biosynthesis and a contact-dependent growth inhibition (CDI) system. ICEPm2 is absent in the P. mirabilis (AR₀156) closest to BL95 and it is present in the genomes of several Escherichia coli from mouse intestines, indicating its recent horizontal mobilization. BL95 shares over 100 genes of five different secretion systems with other P. mirabilis, mostly poorly studied, making a large pool of candidate genes for the contact-dependent growth inhibition.