{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T19:10:49Z","timestamp":1787771449181,"version":"build-2784847793"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T00:00:00Z","timestamp":1698278400000},"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>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Proteus mirabilis<\/jats:italic>\n                      is a key pathobiont in catheter-associated urinary tract infections (CA-UTIs), which is well known to form crystalline biofilms that occlude catheters. Urease activity alkylates urine through the release of ammonia, consequentially resulting in higher levels of Mg\n                      <jats:sup>2+<\/jats:sup>\n                      and Ca\n                      <jats:sup>2+<\/jats:sup>\n                      and formation of crystals. In this study, we showed that\n                      <jats:italic>N<\/jats:italic>\n                      -acetyl cysteine (NAC), a thiol antioxidant, is a potent urease inhibitor that prevents crystalline biofilm formation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To quantify urease activity, Berthelot\u2019s method was done on bacterial extracts treated with NAC. We also used an\n                      <jats:italic>in vitro<\/jats:italic>\n                      catheterised glass bladder model to study the effect of NAC treatment on catheter occlusion and biofilm encrustation in\n                      <jats:italic>P. mirabilis<\/jats:italic>\n                      infections. Inductively-coupled plasma mass spectrometry (ICP-MS) was performed on catheter samples to decipher elemental profiles.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      NAC inhibits urease activity of clinical\n                      <jats:italic>P. mirabilis<\/jats:italic>\n                      isolates at concentrations as low as 1 mM, independent of bacterial killing. The study also showed that NAC is bacteriostatic on\n                      <jats:italic>P. mirabilis<\/jats:italic>\n                      , and inhibited biofilm formation and catheter occlusion in an\n                      <jats:italic>in vitro<\/jats:italic>\n                      . A significant 4-8\n                      <jats:sub>log10<\/jats:sub>\n                      reduction in viable bacteria was observed in catheters infected in this model. Additionally, biofilms in NAC treated catheters displayed a depletion of calcium, magnesium, or phosphates (&amp;gt;10 fold reduction), thus confirming the absence of any urease activity in the presence of NAC. Interestingly, we also showed that not only is NAC anti-inflammatory in bladder epithelial cells (BECs), but that it mutes its inflammatory response to urease and\n                      <jats:italic>P. mirabilis<\/jats:italic>\n                      infection by reducing the production of IL-6, IL-8 and IL-1b.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Using biochemical, microbiological and immunological techniques, this study displays the functionality of NAC in preventing catheter occlusion by inhibiting urease activity. The study also highlights NAC as a strong anti-inflammatory antibiofilm agent that can target both bacterial and host factors in the treatment of CA-UTIs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2023.1216798","type":"journal-article","created":{"date-parts":[[2023,10,28]],"date-time":"2023-10-28T17:38:45Z","timestamp":1698514725000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["N-acetylcysteine prevents catheter occlusion and inflammation in catheter associated-urinary tract infections by suppressing urease activity"],"prefix":"10.3389","volume":"13","author":[{"given":"Arthika","family":"Manoharan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Farrell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vina R.","family":"Aldilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Whiteley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Kriel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor","family":"Glasbey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naresh","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate H.","family":"Moore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jim","family":"Manos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theerthankar","family":"Das","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,10,26]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/5584_2016_197","article-title":"Inhibition of Urease Enzyme Production and some Other Virulence Factors Expression in Proteus mirabilis by N-Acetyl Cysteine and Dipropyl Disulphide","volume-title":"Advances in Microbiology, Infectious Diseases and Public Health: Volume 7","author":"Abdel-Baky","year":"2017"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.3390\/antibiotics10101176","article-title":"Effect of N-acetylcysteine in combination with antibiotics on the biofilms of three cystic fibrosis pathogens of emerging importance","volume":"10","author":"Aiyer","year":"2021","journal-title":"Antibiotics"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1093\/infdis\/169.5.1155","article-title":"The role of swarm cell differentiation and multicellular migration in the uropathogenicity of Proteus mirabilis","volume":"169","author":"Allison","year":"1994","journal-title":"J. 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