CSA-131, a ceragenin active against colistin-resistant Acinetobacter baumannii and Pseudomonas aeruginosa clinical isolates

Vila-Farrés, Xavier; Callarisa, Anna Elena; Gu, Xiaobo; Savage, Paul B.; Giralt, Ernest; Vilà, Jordi

doi:10.1016/j.ijantimicag.2015.08.003

Cited by 31 publications

(27 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…pneumoniae was due to its known pathogenicity and its ability to transfer resistance genes to other Gram-negative bacteria (20, 21). We and our collaborators previously found ceragenins to be active against other colistin-resistant bacteria (19, 22), and we have extended these observations to clinical isolates of K. pneumoniae using additional, later-generation ceragenins.…”

Section: Textsupporting

confidence: 52%

Susceptibility of Colistin-Resistant, Gram-Negative Bacteria to Antimicrobial Peptides and Ceragenins

Hashemi

Rovig

Weber

et al. 2017

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

The susceptibility of colistin-resistant clinical isolates of Klebsiella pneumoniae to ceragenins and antimicrobial peptides (AMPs) suggests that there is little to no cross-resistance between colistin and ceragenins/AMPs and that lipid A modifications are found in bacteria with modest changes in susceptibility to ceragenins and with high levels of resistance to colistin. These results suggest that there are differences in the resistance mechanisms to colistin and ceragenins/AMPs.

show abstract

Section: Textsupporting

confidence: 52%

Susceptibility of Colistin-Resistant, Gram-Negative Bacteria to Antimicrobial Peptides and Ceragenins

Hashemi

Rovig

Weber

et al. 2017

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

show abstract

“…For CSA-13 specifically, HUVEC tube formation and intracellular calcium release were inhibited by ZM 323881, a selective inhibitor for VEGFR2, suggesting that one signaling mechanism activated is the VEGFR2 pathway. Over the past 15 years, ceragenins have shown promise as alternative antimicrobial treatments, effectively inhibiting and killing of numerous species of bacteria, including drug-resistant organisms [16,29]. Our results are consistent with these findings, as many of the ceragenins tested had MICs <10 lgÁmL À1 .…”

Section: Discussionsupporting

confidence: 90%

Antimicrobial ceragenins inhibit biofilms and affect mammalian cell viability and migration in vitro

et al. 2017

Self Cite

View full text Add to dashboard Cite

The healing of burn wounds is often hampered by bacterial infection and the formation of biofilms. Antimicrobial peptides (AMPs) are effective in promoting wound healing, but are susceptible to degradation. We have tested the ability of ceragenins (CSAs), mimics of antimicrobial peptides, to mitigate preformed biofilms and stimulate wound healing in vitro . Potent CSAs (MICs < 10 μg·mL −1 ) were tested against biofilms formed from a mixture of Pseudomonas aeruginosa and Staphylococcus aureus grown for 22 h and subjected to 20 h treatment. Many CSAs showed more potent anti‐biofilm activity than the endogenous AMP LL‐37, and CSA‐13 and CSA‐90 decreased the amount of biofilm matrix substances detected by SYPRO Ruby stain. Effects on mammalian cells were measured by viability, migration, and tube formation assays in vitro . Although CSAs were toxic to immortalized human keratinocytes (HaCaTs) at higher concentrations (>10 μg·mL −1 ), lower concentrations of CSA‐13 and CSA‐192 stimulated cell migration. CSA‐13, CSA‐90, and CSA‐142 also stimulated tube formation in an in vitro angiogenesis model. An inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2) blocked tube formation stimulated by CSA‐13, suggesting that CSA‐13 signals through this receptor. Ceragenins display anti‐biofilm activity and stimulate migration and tube formation in vitro . This work suggests that ceragenins have the potential to be both topical antimicrobials and wound‐healing adjunct therapeutics.

show abstract

“…Vila et al [64] compared the susceptibility of colistin-resistant and susceptible isolates of P. aeruginosa and A. baumannii to ceragenins CSA-13, CSA-44, CSA-131 and CSA-138. MICs were identical or comparable with both the colistin-resistant and susceptible isolates, with MIC90s ranging from 2-8 µg/ml.…”

Section: Antibacterial Activitymentioning

confidence: 99%

Ceragenins as Mimics of Endogenous Antimicrobial Peptides

Hashemi¹,

Holden²,

DurnaÅ³

et al. 2017

J Antimicrob Agents

View full text Add to dashboard Cite

Ceragenins are small molecule mimics of endogenous antimicrobial peptides (AMPs), and as such display broadspectrum antimicrobial activity. These molecules are derived from a common bile acid and can be prepared at a large scale. Because ceragenins are not peptide based, they are not substrates for proteases. Gram-negative and positive bacteria are susceptible to ceragenins, including drug resistant organisms. Although ceragenins and colistin have common features, ceragenins retain full antibacterial activity against colistin-resistant Gram-negative bacteria. Bactericidal activity of ceragenins involves selective association with bacterial membranes followed by membrane depolarization. Due to this mechanism of action, which provides bactericidal activity against sessile bacteria, ceragenins eradicate established biofilms. Lipid-enveloped viruses (e.g. vaccinia) are deactivated by ceragenins, and topical application of a lead ceragenin decreases transmission of the virus in skin in a murine model. More recently, the activities of ceragenins against fungal pathogens have been reported, with minimum inhibition concentrations comparable to clinically used anti-fungal agents. In addition to antimicrobial activities, ceragenins have been shown to display some of the "secondary" activities attributed to AMPs. In vivo use of ceragenins to eradicate biofilms, prevent infection and accelerate bone growth demonstrate some of the types of applications in which ceragenins may be used to augment or replace activities of endogenous AMPs.

show abstract

CSA-131, a ceragenin active against colistin-resistant Acinetobacter baumannii and Pseudomonas aeruginosa clinical isolates

Cited by 31 publications

References 14 publications

Susceptibility of Colistin-Resistant, Gram-Negative Bacteria to Antimicrobial Peptides and Ceragenins

Susceptibility of Colistin-Resistant, Gram-Negative Bacteria to Antimicrobial Peptides and Ceragenins

Antimicrobial ceragenins inhibit biofilms and affect mammalian cell viability and migration in vitro

Ceragenins as Mimics of Endogenous Antimicrobial Peptides

Contact Info

Product

Resources

About