Use of ceragenins as a potential treatment for urinary tract infections.

Urszula Wnorowska, Ewelina Piktel, Bonita Durnaś, Krzysztof Fiedoruk, Paul B Savage, Robert Bucki
Author Information
  1. Urszula Wnorowska: Department of Microbiological and Nanobiomedical Engineering, Medical University of Bialystok, Mickiewicza 2c, 15-222, Bialystok, Poland.
  2. Ewelina Piktel: Department of Microbiological and Nanobiomedical Engineering, Medical University of Bialystok, Mickiewicza 2c, 15-222, Bialystok, Poland.
  3. Bonita Durnaś: Department of Microbiology and Immunology, The Faculty of Health Sciences of the Jan Kochanowski University in Kielce, 25-001, Kielce, Poland.
  4. Krzysztof Fiedoruk: Department of Microbiology, Medical University of Bialystok, Bialystok, Poland.
  5. Paul B Savage: Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, 84602, USA.
  6. Robert Bucki: Department of Microbiological and Nanobiomedical Engineering, Medical University of Bialystok, Mickiewicza 2c, 15-222, Bialystok, Poland. buckirobert@gmail.com. ORCID

Abstract

BACKGROUND: Urinary tract infections (UTIs) are one of the most common bacterial infections. High recurrence rates and the increasing antibiotic resistance among uropathogens constitute a large social and economic problem in current public health. We assumed that combination of treatment that includes the administration ceragenins (CSAs), will reinforce the effect of antimicrobial LL-37 peptide continuously produced by urinary tract epithelial cells. Such treatment might be an innovative approach to enhance innate antibacterial activity against multidrug-resistant E. coli.
METHODS: Antibacterial activity measured using killing assays. Biofilm formation was assessed using crystal violet staining. Viability of bacteria and bladder epithelial cells subjected to incubation with tested agents was determined using MTT assays. We investigated the effects of chosen molecules, both alone and in combinations against four clinical strains of E. coli, obtained from patients diagnosed with recurrent UTI.
RESULTS: We observed that the LL-37 peptide, whose concentration increases at sites of urinary infection, exerts increased bactericidal effect against E. coli when combined with ceragenins CSA-13 and CSA-131.
CONCLUSION: We suggest that the employment of combination of natural peptide LL-37 with synthetic analogs might be a potential solution to treat urinary tract infections caused by drug-resistant bacteria.

Keywords

References

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Grants

  1. UMO-2016/21/N/NZ6/02213/Narodowe Centrum Nauki
  2. N/ST/ZB/18/005/1162/Uniwersytet Medyczny w Bialymstoku

MeSH Term

Anti-Bacterial Agents
Antimicrobial Cationic Peptides
Biofilms
Cell Line
Cell Survival
Drug Resistance, Multiple, Bacterial
Escherichia coli
Humans
Steroids
Urinary Tract Infections
Cathelicidins

Chemicals

Anti-Bacterial Agents
Antimicrobial Cationic Peptides
Steroids
ceragenins
Cathelicidins

Word Cloud

Created with Highcharts 10.0.0tractinfectionsLL-37peptideurinarytreatmentcerageninsEcoliusingUrinaryresistancecombinationeffectepithelialcellsmightactivityassaysbacteriainfectionpotentialBACKGROUND:UTIsonecommonbacterialHighrecurrenceratesincreasingantibioticamonguropathogensconstitutelargesocialeconomicproblemcurrentpublichealthassumedincludesadministrationCSAswillreinforceantimicrobialcontinuouslyproducedinnovativeapproachenhanceinnateantibacterialmultidrug-resistantMETHODS:AntibacterialmeasuredkillingBiofilmformationassessedcrystalvioletstainingViabilitybladdersubjectedincubationtestedagentsdeterminedMTTinvestigatedeffectschosenmoleculesalonecombinationsfourclinicalstrainsobtainedpatientsdiagnosedrecurrentUTIRESULTS:observedwhoseconcentrationincreasessitesexertsincreasedbactericidalcombinedCSA-13CSA-131CONCLUSION:suggestemploymentnaturalsyntheticanalogssolutiontreatcauseddrug-resistantUseBacterialdrugCeragenins

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