{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:55:00Z","timestamp":1789016100672,"version":"build-2803163510"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T00:00:00Z","timestamp":1741824000000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The World Health Organization has identified multi-drug resistant <jats:italic>Klebsiella pneumoniae<\/jats:italic> strains as the highest priority in 2024. Understanding the regulatory routes of virulence features is crucial for the development of novel anti-virulence strategies. SdiA, a LuxR-like quorum sensing (QS) receptor that responds to <jats:italic>N-<\/jats:italic>acyl-homoserine lactones (AHLs), is involved in the regulation of virulence traits in some Gram-negative bacteria. The function of this receptor in the virulence of <jats:italic>K. pneumoniae<\/jats:italic> remains uncertain. The objective of the present study was to elucidate the function of SdiA in <jats:italic>K. pneumoniae<\/jats:italic> biofilm formation and virulence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To this end, a genetic knockout of <jats:italic>sdiA<\/jats:italic> was conducted, and virulence-related phenotypic studies were performed following AHL provision.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and Discussion<\/jats:title><jats:p>The results demonstrate that <jats:italic>sdiA<\/jats:italic> deficiency increases susceptibility to phage infection and human serum resistance, and promotes biofilm maturation and cell filamentation, although no effect on virulence was observed <jats:italic>in vivo<\/jats:italic> in the <jats:italic>Galleria mellonella<\/jats:italic> infection model. On the other hand, C6-HSL promoted <jats:italic>sdiA<\/jats:italic>-dependent biofilm maturation, capsule production and serum resistance while reducing virulence against <jats:italic>G. mellonella<\/jats:italic> in the absence of <jats:italic>sdiA<\/jats:italic>. The addition of C6-HSL did not affect phage susceptibility. The results of this study demonstrate that AHLs and SdiA exert a dual influence on virulence phenotypes, operating both independently and hierarchically. These findings provide new insights into the virulence of <jats:italic>K. pneumoniae<\/jats:italic> and its regulation by SdiA.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2025.1562402","type":"journal-article","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T07:04:26Z","timestamp":1741849466000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Regulatory effects on virulence and phage susceptibility revealed by sdiA mutation in Klebsiella pneumoniae"],"prefix":"10.3389","volume":"15","author":[{"given":"Sergio","family":"Silva-Bea","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Maseda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Otero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Romero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010950","article-title":"Bacterial filamentation during urinary tract infections","volume":"18","author":"Abell-King","year":"2022","journal-title":"PLoS Pathog."},{"key":"B2","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1111\/j.1365-2958.2004.04054.x","article-title":"Cell-to-cell signalling in Escherichia coli and Salmonella enterica","volume":"52","author":"Ahmer","year":"2004","journal-title":"Mol. 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