Ceragenins – a new weapon to fight multidrug resistant bacterial infections

Surel, Urszula; Niemirowicz, Katarzyna; Marzec, Michał; Savage, Paul B.; Bucki, Robert

doi:10.5114/ms.2014.45428

Cited by 25 publications

(22 citation statements)

References 53 publications

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“…Active-release coatings containing ceragenins are attractive because of the bactericidal properties of ceragenins, their activity against established biofilms, their stability in the presence of proteases and other enzymes, and the ease by which they can be manipulated [4,20,83]. Williams et al [99] characterized physical and chemical properties of a coating containing CSA-13 as a novel active release agent in a medical grade polymer coating on fracture fixation plates.…”

Section: Medical Device Coatings Containing Cerageninsmentioning

confidence: 99%

“…As a result, substantial effort is being expended to develop new therapeutics and mechanisms for controlling microbial growth to avoid entering a "post-antibiotic" era in which commonly used antibiotics are no longer effective in treating infections [2,3]. For example, according to the U.S. Center for Disease Control and Prevention (CDC), each year more than two million people in the United States are infected by drugresistant bacteria, and a substantial portion of those infections are caused by multidrug-resistant bacteria [4].…”

Section: Introductionmentioning

confidence: 99%

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Ceragenins as Mimics of Endogenous Antimicrobial Peptides

Hashemi¹,

Holden²,

DurnaÅ³

et al. 2017

J Antimicrob Agents

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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.

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Section: Medical Device Coatings Containing Cerageninsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ceragenins as Mimics of Endogenous Antimicrobial Peptides

Hashemi¹,

Holden²,

DurnaÅ³

et al. 2017

J Antimicrob Agents

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“…11 Modified antimicrobial LL-37 peptides, such as FF/CAP18, and a synthetic antimicrobial peptide mimic, ceragenin CSA-13, also have the potential to suppress growth of colon cancer cells. [12][13][14][15] It was found that expression of LL-37 is reduced during progression of stomach cancer from atrophic gastritis to adenocarcinoma. The modified antimicrobial peptide FF/CAP18 exerts antiproliferative effects on the SAS-H1 squamous carcinoma cell line.…”

Section: Introductionmentioning

confidence: 99%

Magnetic nanoparticles enhance the anticancer activity of cathelicidin LL-37 peptide against colon cancer cells

Niemirowicz¹,

Prokop²,

Wilczewska³

et al. 2015

IJN

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The pleiotropic activity of human cathelicidin LL-37 peptide includes an ability to suppress development of colon cancer cells. We hypothesized that the anticancer activity of LL-37 would improve when attached to the surface of magnetic nanoparticles (MNPs). Using colon cancer culture (DLD-1 cells and HT-29 cells), we evaluated the effects of MNPs, LL-37 peptide, its synthetic analog ceragenin CSA-13, and two novel nanosystems, ie, MNP@LL-37 and MNP@CSA-13, on cancer cell viability and apoptosis. Treatment of cancer cells with the LL-37 peptide linked to MNPs (MNP@LL-37) caused a greater decrease in cell viability and a higher rate of apoptosis compared with treatment using free LL-37 peptide. Additionally, we observed a strong ability of ceragenin CSA-13 and MNP@CSA-13 to induce apoptosis of DLD-1 cells. We found that both nanosystems were successfully internalized by HT-29 cells, and cathelicidin LL-37 and ceragenin CSA-13 might play a key role as novel homing molecules. These results indicate that the previously described anticancer activity of LL-37 peptide against colon cancer cells might be significantly improved using a theranostic approach.

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“…On the other hand, if such mechanisms fail, bacteria trapped in DNA/F-actin networks undergo extensive changes of gene expression leading to the development of bacterial biofilm. Interestingly, the formation of bundles induced by F-actin, DNA or bacteriophages is diminished for synthetic analogues of CAPs, such as ceragenins, which maintain their high antibacterial activity despite the presence of PE at the infection site [46,47]. Importantly, elevated eDNA and NET levels and their accumulation in biological fluids is a factor activating innate immune responses, which considerably affect the development of such diseases as asthma and chronic obstructive pulmonary disease [48], periodontitis [49], antineutrophil cytoplasmic antibody-associated vasculitis (AAV) [29], or cancerassociated thrombosis [50].…”

Section: Condensation Of Dna By Cationic Peptidesmentioning

confidence: 99%

Neutrophil extracellular traps as the main source of eDNA

Cieśluk¹,

Piktel²,

Wątek³

et al. 2017

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Neutrophil extracellular traps (NETs) are web-like structures consisting of decondensed DNA together with accompanying proteins, including histones and antimicrobial peptides released from activated neutrophils as part of the first-line defence against pathogens. Despite the protective role of neutrophils, a number of studies indicate that overproduction of NETs followed by accumulation of extracellular DNA (eDNA) and other negatively-charged polyelectrolytes (PE) such as F-actin, contribute to the pathogenesis of some diseases. Neutrophil extracellular traps are also recognised as the structural and functional support of microbial biofilms and should thus be considered as therapeutic targets. Importantly, the chemical nature of PE permits aggregate formation induced by a number of polycations occurring naturally in the human body, including cationic antimicrobial peptides. This review summarises recent reports focused on the clinical significance of NET-derived eDNA and PE and discusses the potential therapeutic strategies to limit the negative consequences of eDNA accumulation.

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Ceragenins – a new weapon to fight multidrug resistant bacterial infections

Cited by 25 publications

References 53 publications

Ceragenins as Mimics of Endogenous Antimicrobial Peptides

Ceragenins as Mimics of Endogenous Antimicrobial Peptides

Magnetic nanoparticles enhance the anticancer activity of cathelicidin LL-37 peptide against colon cancer cells

Neutrophil extracellular traps as the main source of eDNA

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