{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T04:11:18Z","timestamp":1792642278961,"version":"4.5.0"},"reference-count":155,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T00:00:00Z","timestamp":1672790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000691","name":"Academy of Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000361","name":"Diabetes UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000361","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001704","name":"European Society of Clinical Microbiology and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001704","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000850","name":"National Heart and Lung Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000761","name":"Imperial College London","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000761","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000691","name":"Academy of Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000850","name":"National Heart and Lung Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000292","name":"Cystic Fibrosis Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000292","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p><jats:italic>Pseudomonas aeruginosa<\/jats:italic> is an opportunistic pathogen and a major driver of morbidity and mortality in people with Cystic Fibrosis (CF). The Type VI secretion system (T6SS) is a molecular nanomachine that translocates effectors across the bacterial membrane into target cells or the extracellular environment enabling intermicrobial interaction. <jats:italic>P. aeruginosa<\/jats:italic> encodes three T6SS clusters, the H1-, H2- and H3-T6SS, and numerous orphan islands. Genetic diversity of T6SS-associated effectors in <jats:italic>P. aeruginosa<\/jats:italic> has been noted in reference strains but has yet to be explored in clinical isolates. Here, we perform a comprehensive bioinformatic analysis of the pangenome and T6SS effector genes in 52 high-quality clinical <jats:italic>P. aeruginosa<\/jats:italic> genomes isolated from CF patients and housed in the Personalised Approach to <jats:italic>P. aeruginosa<\/jats:italic> strain repository. We confirm that the clinical CF isolate pangenome is open and principally made up of accessory and unique genes that may provide strain-specific advantages. We observed genetic variability in some effector\/immunity encoding genes and show that several well-characterised <jats:italic>vgrG<\/jats:italic> and <jats:italic>PAAR<\/jats:italic> islands are absent from numerous isolates. Our analysis shows clear evidence of disruption to T6SS genomic loci through transposon, prophage, and mobile genetic element insertions. We identified an orphan <jats:italic>vgrG<\/jats:italic> island in <jats:italic>P. aeruginosa<\/jats:italic> strain PAK and five clinical isolates using <jats:italic>in silico<\/jats:italic> analysis which we denote <jats:italic>vgrG7<\/jats:italic>, predicting a gene within this cluster to encode a Tle2 lipase family effector. Close comparison of T6SS loci in clinical isolates compared to reference <jats:italic>P. aeruginosa<\/jats:italic> strain PAO1 revealed the presence of genes encoding eight new T6SS effectors with the following putative functions: cytidine deaminase, lipase, metallopeptidase, NADase, and pyocin. Finally, the prevalence of characterised and putative T6SS effectors were assessed in 532 publicly available <jats:italic>P. aeruginosa<\/jats:italic> genomes, which suggests the existence of accessory effectors. Our <jats:italic>in silico<\/jats:italic> study of the <jats:italic>P. aeruginosa<\/jats:italic> T6SS exposes a level of genetic diversity at T6SS genomic loci not seen to date within <jats:italic>P. aeruginosa,<\/jats:italic> particularly in CF isolates. As understanding the effector repertoire is key to identifying the targets of T6SSs and its efficacy, this comprehensive analysis provides a path for future experimental characterisation of these mediators of intermicrobial competition and host manipulation.<\/jats:p>","DOI":"10.3389\/fmicb.2022.1042505","type":"journal-article","created":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T16:34:40Z","timestamp":1672850080000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":29,"title":["Diversity and prevalence of type VI secretion system effectors in clinical Pseudomonas aeruginosa isolates"],"prefix":"10.3389","volume":"13","author":[{"given":"Luca A.","family":"Robinson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice C. Z.","family":"Collins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronan A.","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane C.","family":"Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke P.","family":"Allsopp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,4]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1038\/s41586-019-1735-9","article-title":"An interbacterial toxin inhibits target cell growth by synthesizing (p)ppApp","volume":"575","author":"Ahmad","year":"2019","journal-title":"Nature"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1111\/J.1574-6968.2000.TB09345.X","article-title":"The NAD-glycohydrolase (nga) gene of streptococcus pyogenes","volume":"191","author":"Ajdic","year":"2000","journal-title":"FEMS Microbiol. 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