The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection
Abstract
The urinary tract functions in close proximity to the outside environment, yet must remain free of microbial colonization to avoid disease. The mechanisms for establishing an antimicrobial barrier in this area are not completely understood. Here, we describe the production and function of the cathelicidin antimicrobial peptides LL-37, its precursor hCAP-18 and its ortholog CRAMP in epithelial cells of human and mouse urinary tract, respectively. Bacterial contact with epithelial cells resulted in rapid production and secretion of the respective peptides, and in humans LL-37/hCAP-18 was released into urine. Epithelium-derived cathelicidin substantially contributed to the protection of the urinary tract against infection, as shown using CRAMP-deficient and neutrophil-depleted mice. In addition, clinical E. coli strains that were more resistant to LL-37 caused more severe urinary tract infections than did susceptible strains. Thus, cathelicidin seems to be a key factor in mucosal immunity of the urinary tract.
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The antibacterial peptide LL-37 from humans has broad-spectrum antibacterial activity by increasing the membrane permeability of bacteria, neutralizing endotoxins, and suppressing the production of proinflammatory factors.
“The antibacterial peptide LL-37 from humans was found to have broad-spectrum antibacterial activity31–34 by increasing the membrane permeability of bacteria, neutralizing endotoxins, and suppressing the production of proinflammatory factors.35”
From Identification of heptapeptides targeting a lethal bacterial strain in septic mice through an integrative approach (2022) · cites this paper as [34]
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- Authors
- Chromek, M., Slamová, Z., Bergman, P., Kovács, L., Podracká, L., Ehrén, I., Hökfelt, T., Gudmundsson, G. H., Gallo, R. L., Agerberth, B., & Brauner, A.
- Affiliations
- Karolinska University Hospital (SE)
- Karolinska Institutet (SE)
- Comenius University Bratislava (SK)
- University of Iceland (IS)
- University of California San Diego (US)
- Corresponding author
- Brauner, Annelie
- ORCID
- Venue
- Nature Medicine
- Published
- 2006-06
- Volume
- 12
- Issue
- 6
- Pages
- 636-641
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2060483617
- Cited by
- 652
- References
- 45
- Citations by year
- 2026: 18 · 2025: 21 · 2024: 28 · 2023: 25 · 2022: 23 · 2021: 22 · 2020: 25 · 2019: 32 · 2018: 32 · 2017: 29 · 2016: 42 · 2015: 39 · 2014: 44 · 2013: 47 · 2012: 34
- FWCI
- 35.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
- Health Sciences › Medicine › Epidemiology › Urinary Tract Infections Management
- Physical Sciences › Chemistry › Organic Chemistry › Antimicrobial agents and applications
- Keywords
- cathelicidin, LL-37, cramps, antimicrobial peptides, urinary tract infection, epithelial cells, mucosal immunity, Escherichia coli, antimicrobial resistance, neutrophils, innate immunity, urine
- MeSH terms
- Animals, Anti-Infective Agents, Child, Epithelial Cells, Escherichia coli, Escherichia coli Infections, Humans, Kidney Cortex, Mice, Inbred C57BL, Microbial Sensitivity Tests, Neutrophils, Urinary Tract, Urinary Tract Infections, Mice, Knockout, Immunity, Mucosal, Urothelium, Antimicrobial Cationic Peptides, Drug Resistance, Bacterial, Mice, Cathelicidins
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