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The bladder urothelium has a protective GAG layer that primarily consists of chondroitin sulfate (CS), heparan sulfate (HS), and hyaluronic acid (HA), and urinary tract pathogens must either degrade or otherwise circumvent this layer to infect the urothelium. In this study, we investigated GAG degradation by\n                      <jats:italic toggle=\"yes\">Proteus mirabilis,<\/jats:italic>\n                      a common and persistent colonizer of the catheterized urinary tract. Almost all\n                      <jats:italic toggle=\"yes\">P. mirabilis<\/jats:italic>\n                      urinary tract isolates harbor a putative chondroitin endolyase (PMI2127), exolyase (PMI2128), and sulfatase (PMI2124). By generating mutant and complemented strains of these genes, we determined that\n                      <jats:italic toggle=\"yes\">P. mirabilis<\/jats:italic>\n                      strain HI4320 degrades multiple forms of CS under numerous culture conditions, including during growth in human urine, and can use CS degradation products as a carbon source. Sulfatase and endolyase activities were required for efficient degradation of all CS types, while the exolyase only contributed to using CS-B or CS-C as a carbon source. Interestingly, only endolyase activity contributed to colonization in a murine model of catheter-associated urinary tract infection (CAUTI), although the colonization defect was even more pronounced when both the endolyase and exolyase were disrupted. The colonization defect was specific to the CAUTI model, likely due to the impact of catheterization on the GAG landscape of the bladder. Limiting CS degradation by\n                      <jats:italic toggle=\"yes\">P. mirabilis<\/jats:italic>\n                      may therefore reduce the risk of ascending infection in catheterized patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/iai.00223-26","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T16:29:31Z","timestamp":1788366571000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Chondroitin sulfate degradation bolsters\n                    <i>Proteus mirabilis<\/i>\n                    growth and colonization of the catheterized urinary tract"],"prefix":"10.1128","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-5944-7066","authenticated-orcid":false,"given":"Benjamin 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