{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:29:13Z","timestamp":1780446553437,"version":"3.54.1"},"reference-count":72,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,18]],"date-time":"2022-03-18T00:00:00Z","timestamp":1647561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Engineered liposomes composed of the naturally occurring lipids sphingomyelin (Sm) and cholesterol (Ch) have been demonstrated to efficiently neutralize toxins secreted by Gram-positive bacteria such as <jats:italic>Streptococcus pneumoniae<\/jats:italic> and <jats:italic>Staphylococcus aureus<\/jats:italic>. Here, we hypothesized that liposomes are capable of neutralizing cytolytic virulence factors secreted by the Gram-negative pathogen <jats:italic>Pseudomonas aeruginosa<\/jats:italic>. We used the highly virulent cystic fibrosis <jats:italic>P. aeruginosa<\/jats:italic> Liverpool Epidemic Strain LESB58 and showed that sphingomyelin (Sm) and a combination of sphingomyelin with cholesterol (Ch:Sm; 66\u2009mol\/% Ch and 34\u2009mol\/% Sm) liposomes reduced lysis of human bronchial and red blood cells upon challenge with the <jats:italic>Pseudomonas<\/jats:italic> secretome. Mass spectrometry of liposome-sequestered <jats:italic>Pseudomonas<\/jats:italic> proteins identified the virulence-promoting hemolytic phospholipase C (PlcH) as having been neutralized. <jats:italic>Pseudomonas aeruginosa<\/jats:italic> supernatants incubated with liposomes demonstrated reduced PlcH activity as assessed by the <jats:italic>p<\/jats:italic>-nitrophenylphosphorylcholine (NPPC) assay. Testing the <jats:italic>in vivo<\/jats:italic> efficacy of the liposomes in a murine cutaneous abscess model revealed that Sm and Ch:Sm, as single dose treatments, attenuated abscesses by &amp;gt;30%, demonstrating a similar effect to that of a mutant lacking <jats:italic>plcH<\/jats:italic> in this infection model. Thus, sphingomyelin-containing liposome therapy offers an interesting approach to treat and reduce virulence of complex infections caused by <jats:italic>P. aeruginosa<\/jats:italic> and potentially other Gram-negative pathogens expressing <jats:italic>PlcH<\/jats:italic>.<\/jats:p>","DOI":"10.3389\/fmicb.2022.867449","type":"journal-article","created":{"date-parts":[[2022,3,18]],"date-time":"2022-03-18T08:55:05Z","timestamp":1647593705000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Targeting the Pseudomonas aeruginosa Virulence Factor Phospholipase C With Engineered Liposomes"],"prefix":"10.3389","volume":"13","author":[{"given":"Heidi","family":"Wolfmeier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel J. T.","family":"Wardell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo T.","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Falsafi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Draeger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduard B.","family":"Babiychuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Pletzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert E. 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