Infection and immunity
September 1, 2026 · via Europe PMC
Chondroitin sulfate degradation bolsters <i>Proteus mirabilis</i> growth and colonization of the catheterized urinary tract.
Hunt BC, Brix V, Deka N, Learman BS, Brauer AL, Shipman BM, De Nisco NJ, Armbruster CE.
AI summary — for doctors, generated from the abstract only
Proteus mirabilis degrades bladder chondroitin sulfate for growth, and its endolyase contributes to colonization specifically in a mouse model of catheter-associated urinary tract infection.
What was studied
A preclinical study characterized putative chondroitin endolyase, exolyase, and sulfatase genes in P. mirabilis using mutant and complemented strains, assessing chondroitin sulfate degradation in culture and human urine and colonization in a murine catheter-associated urinary tract infection model.
Key findings
- Nearly all P. mirabilis urinary isolates carry the putative endolyase, exolyase, and sulfatase genes.
- Strain HI4320 degraded multiple chondroitin sulfate forms, including in human urine, and used degradation products as a carbon source.
- Sulfatase and endolyase activities were needed for efficient degradation of all chondroitin sulfate types; the exolyase contributed only to using CS-B or CS-C as carbon source.
- Only endolyase activity contributed to colonization in the catheter model, with a more pronounced defect when both endolyase and exolyase were disrupted; the defect was specific to the catheterized model.
Clinical relevance
These bacterial genetics and mouse-model findings propose chondroitin sulfate degradation as a possible target in catheter-associated infection, but no human or therapeutic evidence exists.
Who should care
Limitations
Single strain in in vitro assays and a murine catheter model, which may not reproduce human bladder conditions.
Breaking down the bladder's protective sugar layer appears to help Proteus establish catheter-associated infection in mice.
This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.
Abstract
Glycosaminoglycans (GAGs) are negatively charged polysaccharides composed of repeating disaccharide units and are essential components of the extracellular matrix throughout numerous tissues. 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 Proteus mirabilis, a common and persistent colonizer of the catheterized urinary tract. Almost all P. mirabilis 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 P. mirabilis 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 P. mirabilis may therefore reduce the risk of ascending infection in catheterized patients.
Glycosaminoglycans (GAGs) are negatively charged polysaccharides composed of repeating disaccharide units and are essential components of the extracellular matrix throughout numerous tissues. 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 Proteus mirabilis, a common and persistent colonizer of the catheterized urinary tract. Almost all P. mirabilis 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 P. mirabilis 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 P. mirabilis may therefore reduce the risk of ascending infection in catheterized patients.
DOI
10.1128/iai.00223-26
PMID
42684860
Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.
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