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The nature of these systems can be complex and they are, for the most part, poorly understood at the polymicrobial level. The Pseudomonas Quinolone Signal (PQS) and its precursor 4-hydroxy-2-heptylquinoline (HHQ) are signal molecules produced by the important nosocomial pathogen <jats:italic>\n                     <jats:named-content content-type=\"species\">\n                        <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/doi.org\/10.1601\/nm.2553\" xlink:type=\"simple\">Pseudomonas aeruginosa<\/jats:ext-link>\n                     <\/jats:named-content>\n                  <\/jats:italic>. They are known to modulate the behaviour of co-colonizing bacterial and fungal pathogens such as <jats:italic>Bacillus atropheaus<\/jats:italic>, <jats:italic>Candida albicans<\/jats:italic> and <jats:italic>Aspergillus fumigatus<\/jats:italic>. While the structural basis for alkyl-quinolone signalling within <jats:italic>\n                     <jats:named-content content-type=\"species\">\n                        <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/doi.org\/10.1601\/nm.2553\" xlink:type=\"simple\">P. aeruginosa<\/jats:ext-link>\n                     <\/jats:named-content>\n                  <\/jats:italic> has been studied extensively, less is known about how structural derivatives of these molecules can influence multicellular behaviour and population-level decision-making in other co-colonizing organisms. In this study, we investigated a suite of small molecules derived initially from the HHQ framework, for anti-virulence activity against ESKAPE pathogens, at the species and strain levels. Somewhat surprisingly, with appropriate substitution, loss of the alkyl chain (present in HHQ and PQS) did not result in a loss of activity, presenting a more easily accessible synthetic framework for investigation. Virulence profiling uncovered significant levels of inter-strain variation among the responses of clinical and environmental isolates to small-molecule challenge. While several lead compounds were identified in this study, further work is needed to appreciate the extent of strain-level tolerance to small-molecule anti-infectives among pathogenic organisms.<\/jats:p>","DOI":"10.1099\/mic.0.001303","type":"journal-article","created":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T18:18:21Z","timestamp":1677781101000},"source":"Crossref","is-referenced-by-count":1,"title":["Structural modification of the Pseudomonas aeruginosa alkylquinoline cell\u2013cell communication signal, HHQ, leads to benzofuranoquinolines with anti-virulence behaviour in ESKAPE pathogens"],"prefix":"10.1099","volume":"169","author":[{"given":"Veronica","family":"Rossetto","sequence":"first","affiliation":[{"name":"School of Microbiology, University College Cork, Cork, Ireland"},{"name":"Faculty of Science and Technology, Universidade do Algarve, Algarve, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ay'sha","family":"Moore-Machacek","sequence":"additional","affiliation":[{"name":"School of Microbiology, University College Cork, Cork, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David F.","family":"Woods","sequence":"additional","affiliation":[{"name":"School of Microbiology, University College Cork, Cork, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helena M.","family":"Galv\u00e3o","sequence":"additional","affiliation":[{"name":"Faculty of Science and Technology, Universidade do Algarve, Algarve, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel M.","family":"Shanahan","sequence":"additional","affiliation":[{"name":"School of Chemistry and Analytical and Biological Chemistry Research Facility, University College Cork, Cork, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aobha","family":"Hickey","sequence":"additional","affiliation":[{"name":"School of Chemistry and Analytical and Biological Chemistry Research Facility, University College Cork, Cork, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niall","family":"O\u2019Leary","sequence":"additional","affiliation":[{"name":"School of Microbiology, University College Cork, Cork, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fergal","family":"O\u2019Gara","sequence":"additional","affiliation":[{"name":"Wal-yan Respiratory Research Centre, Telethon Kids Institute, Perth, WA, Australia"},{"name":"Biomerit Research Centre, School of Microbiology, University College Cork, Cork, Ireland"},{"name":"School of Microbiology, University College Cork, Cork, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerard P.","family":"McGlacken","sequence":"additional","affiliation":[{"name":"Synthesis and Solid State Pharmaceutical Centre, University College Cork, Cork, Ireland"},{"name":"School of Chemistry and Analytical and Biological Chemistry Research Facility, University College Cork, Cork, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7717-9892","authenticated-orcid":false,"given":"F. 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