{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T02:43:58Z","timestamp":1768790638626,"version":"3.49.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T00:00:00Z","timestamp":1632182400000},"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>Background<\/jats:title><jats:p>Bacterial biofilms generally contribute to chronic infections and complicate effective treatment outcomes. To date, there have been no reports describing biofilm formation in animal models of septic arthritis caused by <jats:italic>Pseudomonas aeruginosa<\/jats:italic> (<jats:italic>P. aeruginosa<\/jats:italic>). <jats:italic>P. aeruginosa<\/jats:italic> is an opportunistic pathogenic bacterium which can lead to septic arthritis. The purpose of this study was to establish a rabbit model of septic arthritis caused by <jats:italic>P. aeruginosa<\/jats:italic> to determine whether it leads to biofilm formation in the knee joint cavity. In addition, we explored the role of cyclic di-GMP (c-di-GMP) concentrations in biofilm formation in rabbit models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twenty rabbits were randomly assigned to five groups: PAO1 (n = 4), PAO1<jats:italic>\u0394wspF<\/jats:italic> (n = 4), PAO1<jats:italic>\/p<jats:sub>lac<\/jats:sub>-yhjH<\/jats:italic> (n = 4) infection group, Luria\u2013Bertani (LB) broth (n\u00a0= 4), and magnesium tetrasilicate (talc) (n = 4) control groups. Inoculation in the rabbit knee of <jats:italic>P. aeruginosa<\/jats:italic> or with the same volume of sterile LB or talc in suspension (control group) was used to induce septic arthritis in the animal model. In the infection groups, septic arthritis was caused by PAO1, PAO1<jats:italic>\u0394wspF<\/jats:italic>, and PAO1<jats:italic>\/p<jats:sub>lac<\/jats:sub>-yhjH<\/jats:italic> strains, respectively. Rabbits were euthanized after 7 days, and pathological examination of synovial membrane was performed. The biofilms on the surface of the synovial membrane were observed by scanning electron microscopy, while the biofilms\u2019 fiber deposition was discriminated using peptide nucleic acid-fluorescence <jats:italic>in situ<\/jats:italic> hybridization (PNA-FISH).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A rabbit model for knee septic arthritis induced by <jats:italic>P. aeruginosa<\/jats:italic> was successfully established. Scanning electron microscopy revealed that PAO1 strains were surrounded in a self-produced extracellular matrix on the surface of synovial membrane and showed biofilm structures. The biofilms in the fibrous deposition were also observed by PNA-FISH. The PNA-FISH assay revealed that the red fluorescence size in the PAO1<jats:italic>\u0394wspF<\/jats:italic> group was greater than in PAO1 and PAO1<jats:italic>\/p<jats:sub>lac<\/jats:sub>-yhjH<\/jats:italic> groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This is the first study to provide evidence that <jats:italic>P. aeruginosa<\/jats:italic> forms biofilms in a rabbit model for septic knee arthritis. The rabbit model can be used to investigate new approaches to treatment of biofilms in septic arthritis. Furthermore, c-di-GMP is a key signaling molecule which impacts on biofilm formation in rabbit models of knee septic\u00a0arthritis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2021.724113","type":"journal-article","created":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T05:16:49Z","timestamp":1632201409000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Biofilm Formation by Pseudomonas aeruginosa in a Novel Septic Arthritis Model"],"prefix":"10.3389","volume":"11","author":[{"given":"Dingbin","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinhua","family":"Liang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wusheng","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingjun","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,21]]},"reference":[{"key":"B3","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/s1473-3099(19)30419-0","article-title":"Mortality and Adverse Joint Outcomes Following Septic Arthritis of the Native Knee: A Longitudinal Cohort Study of Patients Receiving Arthroscopic Washout","volume":"20","author":"Abram","year":"2020","journal-title":"Lancet Infect. 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