Ceragenins exhibit bactericidal properties that are independent of the ionic strength in the environment mimicking cystic fibrosis sputum

Skłodowski, Karol; Suprewicz, Łukasz; Chmielewska-Deptuła, Sylwia Joanna; Kaliniak, Szczepan; Okła, Sławomir; Zakrzewska, Magdalena; Minarowski, Łukasz; Mróz, Robert; Daniluk, Tamara; Savage, Paul B.; Fiedoruk, Krzysztof; Bucki, Robert

doi:10.3389/fmicb.2023.1290952

Cited by 2 publications

(1 citation statement)

References 82 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nevertheless, for a more reliable assessment of ceragenin antibiofilm efficacy, experiments must be performed under conditions mimicking CF lungs, such as artificial sputum media (ASM), synthetic cystic fibrosis media (SCFM), or CF sputum samples. Accordingly, we recently reported that ceragenins preserve bactericidal activity in the environment mimicking CF sputum irrespective of its ionic strength [ 66 ]. Furthermore, the effect of the microbial cell morphology [ 56 ] and Pf bacteriophages representing various phylogenetic lineages [ 21 ] on the viscoelastic properties of biofilms should be addressed in further studies.…”

Section: Discussionmentioning

confidence: 99%

Ceragenin-mediated disruption of Pseudomonas aeruginosa biofilms

Wnorowska,

Łysik,

Piktel

et al. 2024

PLoS ONE

Self Cite

View full text Add to dashboard Cite

Background Microbial biofilms, as a hallmark of cystic fibrosis (CF) lung disease and other chronic infections, remain a desirable target for antimicrobial therapy. These biopolymer-based viscoelastic structures protect pathogenic organisms from immune responses and antibiotics. Consequently, treatments directed at disrupting biofilms represent a promising strategy for combating biofilm-associated infections. In CF patients, the viscoelasticity of biofilms is determined mainly by their polymicrobial nature and species-specific traits, such as Pseudomonas aeruginosa filamentous (Pf) bacteriophages. Therefore, we examined the impact of microbicidal ceragenins (CSAs) supported by mucolytic agents–DNase I and poly-aspartic acid (pASP), on the viability and viscoelasticity of mono- and bispecies biofilms formed by Pf-positive and Pf-negative P. aeruginosa strains co-cultured with Staphylococcus aureus or Candida albicans. Methods The in vitro antimicrobial activity of ceragenins against P. aeruginosa in mono- and dual-species cultures was assessed by determining minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC). Inhibition of P. aeruginosa mono- and dual-species biofilms formation by ceragenins alone and in combination with DNase I or poly-aspartic acid (pASP) was estimated by the crystal violet assay. Additionally, the viability of the biofilms was measured by colony-forming unit (CFU) counting. Finally, the biofilms’ viscoelastic properties characterized by shear storage (G’) and loss moduli (G”), were analyzed with a rotational rheometer. Results Our results demonstrated that ceragenin CSA-13 inhibits biofilm formation and increases its fluidity regardless of the Pf-profile and species composition; however, the Pf-positive biofilms are characterized by elevated viscosity and elasticity parameters. Conclusion Due to its microbicidal and viscoelasticity-modifying properties, CSA-13 displays therapeutic potential in biofilm-associated infections, especially when combined with mucolytic agents.

show abstract

Section: Discussionmentioning

confidence: 99%

Ceragenin-mediated disruption of Pseudomonas aeruginosa biofilms

Wnorowska,

Łysik,

Piktel

et al. 2024

PLoS ONE

Self Cite

View full text Add to dashboard Cite

show abstract

Efficacy of Tamoxifen Metabolites in Combination with Colistin and Tigecycline in Experimental Murine Models of Escherichia coli and Acinetobacter baumannii

Herrera-Espejo,

Vila-Domínguez,

Cebrero-Cangueiro

et al. 2024

Antibiotics

View full text Add to dashboard Cite

This study aimed to evaluate the potential of tamoxifen and N-desmethyltamoxifen metabolites as therapeutic agents against multidrug-resistant Escherichia coli and Acinetobacter baumannii, using a repurposing approach to shorten the time required to obtain a new effective treatment against multidrug-resistant bacterial infections. Characterisation and virulence studies were conducted on E. coli (colistin-susceptible C1-7-LE and colistin-resistant MCR-1+) and A. baumannii (tigecycline-susceptible Ab#9 and tigecycline-resistant Ab#186) strains. The efficacy of the metabolite mix (33.3% each) and N-desmethyltamoxifen in combination with colistimethate sodium (CMS) or tigecycline was evaluated in experimental models in mice. In the pneumonia model, N-desmethyltamoxifen exhibited significant efficacy against Ab#9 and both E. coli strains, especially E. coli MCR-1+ (−2.86 log10 CFU/g lungs, −5.88 log10 CFU/mL blood, and −50% mortality), and against the Ab#186 strain when combined with CMS (−2.27 log10 CFU/g lungs, −2.73 log10 CFU/mL blood, and −40% mortality) or tigecycline (−3.27 log10 CFU/g lungs, −4.95 log10 CFU/mL blood, and −50% mortality). Moreover, the metabolite mix in combination with both antibiotics decreased the bacterial concentrations in the lungs and blood for both A. baumannii strains. In the sepsis model, the significant efficacy of the metabolite mix was restricted to the colistin-susceptible E. coli C1-7-LE strain (−3.32 log10 CFU/g lung, −6.06 log10 CFU/mL blood, and −79% mortality). N-desmethyltamoxifen could be a new therapeutic option in combination with CMS or tigecycline for combating multidrug-resistant GNB, specifically A. baumannii.

show abstract

Ceragenins exhibit bactericidal properties that are independent of the ionic strength in the environment mimicking cystic fibrosis sputum

Cited by 2 publications

References 82 publications

Ceragenin-mediated disruption of Pseudomonas aeruginosa biofilms

Ceragenin-mediated disruption of Pseudomonas aeruginosa biofilms

Efficacy of Tamoxifen Metabolites in Combination with Colistin and Tigecycline in Experimental Murine Models of Escherichia coli and Acinetobacter baumannii

Contact Info

Product

Resources

About