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To understand how and why LTTR proteins evolved with such frequency and to establish whether any relationships exist within the distribution we set out to identify the patterns underpinning LTTR distribution in <jats:italic>P. aeruginosa<\/jats:italic> and to uncover cluster-based relationships within the pangenome. Comparative genomic studies revealed that in the JGI IMG database alone ~86\u200a000 LTTRs are present across the sequenced genomes (<jats:italic>n<\/jats:italic>=699). They are widely distributed across the species, with core LTTRs present in &gt;93\u200a% of the genomes and accessory LTTRs present in &lt;7\u200a%. Analysis showed that subsets of core LTTRs can be classified as either variable (typically specific to <jats:italic>P. aeruginosa<\/jats:italic>) or conserved (and found to be distributed in other <jats:italic>Pseudomonas<\/jats:italic> species). Extending the analysis to the more extensive Pseudomonas database, PA14 rooted analysis confirmed the diversification patterns and revealed PqsR, the receptor for the Pseudomonas quinolone signal (PQS) and 2-heptyl-4-quinolone (HHQ) quorum-sensing signals, to be amongst the most variable in the dataset. Successful complementation of the PAO1 <jats:italic>pqsR<\/jats:italic>\n                  <jats:sup>-<\/jats:sup> mutant using representative variant <jats:italic>pqsR<\/jats:italic> sequences suggests a degree of structural promiscuity within the most variable of LTTRs, several of which play a prominent role in signalling and communication. These findings provide a new insight into the diversification of LTTR proteins within the <jats:italic>P. aeruginosa<\/jats:italic> species and suggests a functional significance to the cluster, conservation and distribution patterns identified.<\/jats:p>","DOI":"10.1099\/mgen.0.001205","type":"journal-article","created":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T15:17:00Z","timestamp":1709219820000},"source":"Crossref","is-referenced-by-count":2,"title":["Comparative genomics reveals distinct diversification patterns among LysR-type transcriptional regulators in the ESKAPE pathogen Pseudomonas aeruginosa"],"prefix":"10.1099","volume":"10","author":[{"given":"Jamie","family":"Deery","sequence":"first","affiliation":[{"name":"School of Microbiology, University College Cork, Cork, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muireann","family":"Carmody","sequence":"additional","affiliation":[{"name":"School of Chemistry, University College Cork, Cork, Ireland"},{"name":"School of Microbiology, University College Cork, Cork, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhiannon","family":"Flavin","sequence":"additional","affiliation":[{"name":"School of Microbiology, University College Cork, Cork, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malwina","family":"Tomanek","sequence":"additional","affiliation":[{"name":"School of Microbiology, University College Cork, Cork, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"O'Keeffe","sequence":"additional","affiliation":[{"name":"School of Microbiology, University College Cork, Cork, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard P.","family":"McGlacken","sequence":"additional","affiliation":[{"name":"Synthesis and Solid State Pharmaceutical Centre, University College Cork, Cork, Ireland"},{"name":"School of Chemistry, University College Cork, Cork, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7717-9892","authenticated-orcid":false,"given":"F. 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