Abstract
BackgroundUrinary 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.MethodsAntibacterial 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.ResultsWe 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.ConclusionWe 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.
Highlights
Urinary tract infections (UTIs) are one of the most common bacterial infections
Antimicrobial activity of LL-37, DOX and ceragenins agents against extracellular bacteria To determine the bactericidal activities of LL-37, DOX and ceragenins against extracellular E.coli strains, we used a conventional bacterial killing assay (Fig. 1) and Minimal inhibitory concentrations (MIC)/Minimal bactericidal concentration (MBC) measurements (Table 2)
Susceptibility data from our experiments demonstrate that ceragenins (CSA-13, CSA-131) have stronger bactericidal activities against E. coli than LL-37 or doxycycline against clinical strains of pathogen
Summary
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 multidrugresistant E. coli. High recurrence rates and progressively increasing resistance of microorganisms to conventional antibiotics, especially among carbapenem-resistant Enterobacteriaceae, makes UTIs a serious social and economic problem [4,5,6]. It should be noted that some conventional antibiotics used conventionally to fight UTIs, such as fluoroquinolones or
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