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Artikel: Effects of Ceragenins and Antimicrobial Peptides on the A549 Cell Line and an In Vitro Co-Culture Model of A549 Cells and

Oyardi, Ozlem / Savage, Paul B / Guzel, Cagla Bozkurt

2022 Band 11, Heft 9

Abstract: Pseudomonas ... ...

Abstract	Pseudomonas aeruginosa
Sprache	Englisch
Erscheinungsdatum	2022-09-14
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens11091044
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Efficacy of Ceragenins Alone and in Combinations with Antibiotics Against Multidrug-Resistant Gram Negative Pathogens from Bloodstream Infections.

Yilmaz, Fatima Nur / Öksüz, Lütfiye / Demir, Elif Sena / Döşler, Sibel / Savage, Paul B / Güzel, Çağla Bozkurt

Current microbiology

2023 Band 80, Heft 10, Seite(n) 327

Abstract: Ceragenins (CSAs) that mimic the activities of antimicrobial peptides may be new options for the treatment of infections caused by multidrug-resistant pathogens. This study investigated the antibacterial activities of eight different ceragenins against ... ...

Abstract	Ceragenins (CSAs) that mimic the activities of antimicrobial peptides may be new options for the treatment of infections caused by multidrug-resistant pathogens. This study investigated the antibacterial activities of eight different ceragenins against MDR pathogens and the synergistic effects of some ceragenins in combinations with antibiotics (meropenem-MEM, ceftazidime + avibactam-CZA, tigecycline-TIG). A disc diffusion method was used for antibiotic susceptibility tests, a broth microdilution, and checkerboard methods were used to detect minimum inhibitory concentrations (MICs) and the effects of combinations, respectively. While MIC
Mesh-Begriff(e)	Humans ; Anti-Bacterial Agents/pharmacology ; Escherichia coli ; Sepsis ; Meropenem ; Pseudomonas aeruginosa
Chemische Substanzen	Anti-Bacterial Agents ; ceragenins ; Meropenem (FV9J3JU8B1)
Sprache	Englisch
Erscheinungsdatum	2023-08-24
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	134238-1
ISSN	1432-0991 ; 0343-8651
ISSN (online)	1432-0991
ISSN	0343-8651
DOI	10.1007/s00284-023-03443-5
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Glyoxylate Shunt and Pyruvate-to-Acetoin Shift Are Specific Stress Responses Induced by Colistin and Ceragenin CSA-13 in Enterobacter hormaechei ST89.

Prasad, Suhanya V / Fiedoruk, Krzysztof / Zakrzewska, Magdalena / Savage, Paul B / Bucki, Robert

Microbiology spectrum

2023 Band 11, Heft 4, Seite(n) e0121523

Abstract: Ceragenins, including CSA-13, are cationic antimicrobials that target the bacterial cell envelope differently than colistin. However, the molecular basis of their action is not fully understood. Here, we examined the genomic and transcriptome responses ... ...

Abstract	Ceragenins, including CSA-13, are cationic antimicrobials that target the bacterial cell envelope differently than colistin. However, the molecular basis of their action is not fully understood. Here, we examined the genomic and transcriptome responses by Enterobacter hormaechei after prolonged exposure to either CSA-13 or colistin. Resistance of the
Mesh-Begriff(e)	Colistin/pharmacology ; Anti-Bacterial Agents/pharmacology ; Acetoin ; Pyruvic Acid ; Drug Resistance, Bacterial/genetics ; Anti-Infective Agents/pharmacology ; Glyoxylates ; Microbial Sensitivity Tests ; Bacterial Proteins/genetics
Chemische Substanzen	Colistin (Z67X93HJG1) ; Anti-Bacterial Agents ; ceragenin CSA-13 ; Acetoin (BG4D34CO2H) ; Pyruvic Acid (8558G7RUTR) ; Anti-Infective Agents ; Glyoxylates ; Bacterial Proteins
Sprache	Englisch
Erscheinungsdatum	2023-06-20
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/spectrum.01215-23
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Fragment-based drug discovery for disorders of the central nervous system: designing better drugs piece by piece.

Chan, Bill W G L / Lynch, Nicholas B / Tran, Wendy / Joyce, Jack M / Savage, G Paul / Meutermans, Wim / Montgomery, Andrew P / Kassiou, Michael

Frontiers in chemistry

2024 Band 12, Seite(n) 1379518

Abstract: Fragment-based drug discovery (FBDD) has emerged as a powerful strategy to confront the challenges faced by conventional drug development approaches, particularly in the context of central nervous system (CNS) disorders. FBDD involves the screening of ... ...

Abstract	Fragment-based drug discovery (FBDD) has emerged as a powerful strategy to confront the challenges faced by conventional drug development approaches, particularly in the context of central nervous system (CNS) disorders. FBDD involves the screening of libraries that comprise thousands of small molecular fragments, each no greater than 300 Da in size. Unlike the generally larger molecules from high-throughput screening that limit customisation, fragments offer a more strategic starting point. These fragments are inherently compact, providing a strong foundation with good binding affinity for the development of drug candidates. The minimal elaboration required to transition the hit into a drug-like molecule is not only accelerated, but also it allows for precise modifications to enhance both their activity and pharmacokinetic properties. This shift towards a fragment-centric approach has seen commercial success and holds considerable promise in the continued streamlining of the drug discovery and development process. In this review, we highlight how FBDD can be integrated into the CNS drug discovery process to enhance the exploration of a target. Furthermore, we provide recent examples where FBDD has been an integral component in CNS drug discovery programs, enabling the improvement of pharmacokinetic properties that have previously proven challenging. The FBDD optimisation process provides a systematic approach to explore this vast chemical space, facilitating the discovery and design of compounds piece by piece that are capable of modulating crucial CNS targets.
Sprache	Englisch
Erscheinungsdatum	2024-04-18
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article ; Review
ZDB-ID	2711776-5
ISSN	2296-2646
ISSN	2296-2646
DOI	10.3389/fchem.2024.1379518
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: The Use of Social Media to Express and Manage Medical Uncertainty in Dyskeratosis Congenita: Content Analysis.

Pearce, Emily / Raj, Hannah / Emezienna, Ngozika / Gilkey, Melissa B / Lazard, Allison J / Ribisl, Kurt M / Savage, Sharon A / Han, Paul Kj

JMIR infodemiology

2024 Band 4, Seite(n) e46693

Abstract: Background: Social media has the potential to provide social support for rare disease communities; however, little is known about the use of social media for the expression of medical uncertainty, a common feature of rare diseases.: Objective: This ... ...

Abstract	Background: Social media has the potential to provide social support for rare disease communities; however, little is known about the use of social media for the expression of medical uncertainty, a common feature of rare diseases. Objective: This study aims to evaluate the expression of medical uncertainty on social media in the context of dyskeratosis congenita, a rare cancer-prone inherited bone marrow failure and telomere biology disorder (TBD). Methods: We performed a content analysis of uncertainty-related posts on Facebook and Twitter managed by Team Telomere, a patient advocacy group for this rare disease. We assessed the frequency of uncertainty-related posts, uncertainty sources, issues, and management and associations between uncertainty and social support. Results: Across all TBD social media platforms, 45.98% (1269/2760) of posts were uncertainty related. Uncertainty-related posts authored by Team Telomere on Twitter focused on scientific (306/434, 70.5%) or personal (230/434, 53%) issues and reflected uncertainty arising from probability, ambiguity, or complexity. Uncertainty-related posts in conversations among patients and caregivers in the Facebook community group focused on scientific (429/511, 84%), personal (157/511, 30.7%), and practical (114/511, 22.3%) issues, many of which were related to prognostic unknowns. Both platforms suggested uncertainty management strategies that focused on information sharing and community building. Posts reflecting response-focused uncertainty management strategies (eg, emotional regulation) were more frequent on Twitter compared with the Facebook community group (χ Conclusions: Although uncertainty is a pervasive and multifactorial issue in TBDs, our findings suggest that the discussion of medical uncertainty on TBD social media is largely limited to brief exchanges about scientific, personal, or practical issues rather than ongoing supportive conversation. The nature of uncertainty-related conversations also varied by user group: patients and caregivers used social media primarily to discuss scientific uncertainties (eg, regarding prognosis), form social connections, or exchange advice on accessing and organizing medical care, whereas Team Telomere used social media to express scientific and personal issues of uncertainty and to address the emotional impact of uncertainty. The higher involvement of female parents on TBD social media suggests a potentially greater burden of uncertainty management among mothers compared with other groups. Further research is needed to understand the dynamics of social media engagement to manage medical uncertainty in the TBD community.
Mesh-Begriff(e)	Humans ; Female ; Uncertainty ; Social Media ; Dyskeratosis Congenita/genetics ; Rare Diseases ; Probability
Sprache	Englisch
Erscheinungsdatum	2024-01-15
Erscheinungsland	Canada
Dokumenttyp	Journal Article
ISSN	2564-1891
ISSN (online)	2564-1891
DOI	10.2196/46693
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Effects of Ceragenins and Antimicrobial Peptides on the A549 Cell Line and an In Vitro Co-Culture Model of A549 Cells and Pseudomonas aeruginosa

Oyardi, Ozlem / Savage, Paul B. / Guzel, Cagla Bozkurt

Pathogens. 2022 Sept. 14, v. 11, no. 9

2022

Abstract: Pseudomonas aeruginosa is an important pathogen that can adhere to host tissues and epithelial surfaces, especially during chronic infections such as cystic fibrosis (CF) lung infections. The effect of ceragenins and antimicrobial peptides (AMP) on this ... ...

Abstract	Pseudomonas aeruginosa is an important pathogen that can adhere to host tissues and epithelial surfaces, especially during chronic infections such as cystic fibrosis (CF) lung infections. The effect of ceragenins and antimicrobial peptides (AMP) on this colonization was investigated in a co-culture infection model. After determining the antimicrobial effects of the substances on P. aeruginosa planktonic cells, their cytotoxicity on the A549 cell line was also determined. After the A549 cell line was infected with P. aeruginosa, the effect of antimicrobials on intracellular bacteria as well as the effects in inhibiting the adhesion of P. aeruginosa were investigated. In addition, LDH release from cells was determined by performing an LDH experiment to understand the cytotoxicity of bacterial infection and antimicrobial treatment on cells. CSA-131 was determined as the antimicrobial agent with the highest antimicrobial activity, while the antimicrobial effects of AMPs were found to be much lower than those of ceragenins. The antimicrobial with the lowest IC₅₀ value was determined as the combination of CSA-131 with Pluronic F127. CSA-13 has been determined to be the most effective antimicrobial with its effectiveness to both intracellular bacteria and bacterial adhesion. Nevertheless, further safety, efficacy, toxicity, and pharmacological studies of ceragenins are needed to evaluate clinical utility.
Schlagwörter	Pseudomonas aeruginosa ; adhesion ; anti-infective agents ; antimicrobial peptides ; antimicrobial properties ; bacterial adhesion ; bacterial infections ; cell lines ; coculture ; cystic fibrosis ; cytotoxicity ; epithelium ; lungs ; models ; pathogens ; plankton
Sprache	Englisch
Erscheinungsverlauf	2022-0914
Erscheinungsort	Multidisciplinary Digital Publishing Institute
Dokumenttyp	Artikel
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens11091044
Datenquelle	NAL Katalog (AGRICOLA)

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Artikel ; Online: Ceragenin-mediated disruption of Pseudomonas aeruginosa biofilms.

Wnorowska, Urszula / Łysik, Dawid / Piktel, Ewelina / Zakrzewska, Magdalena / Okła, Sławomir / Lesiak, Agata / Spałek, Jakub / Mystkowska, Joanna / Savage, Paul B / Janmey, Paul / Fiedoruk, Krzysztof / Bucki, Robert

PloS one

2024 Band 19, Heft 2, Seite(n) e0298112

Abstract: 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 ...

Abstract	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.
Mesh-Begriff(e)	Humans ; Pseudomonas aeruginosa ; Aspartic Acid ; Expectorants ; Anti-Bacterial Agents/pharmacology ; Anti-Infective Agents/pharmacology ; Biofilms ; Cystic Fibrosis ; Deoxyribonuclease I ; Microbial Sensitivity Tests ; Pseudomonas Infections ; Steroids
Chemische Substanzen	ceragenins ; Aspartic Acid (30KYC7MIAI) ; Expectorants ; Anti-Bacterial Agents ; Anti-Infective Agents ; Deoxyribonuclease I (EC 3.1.21.1) ; Steroids
Sprache	Englisch
Erscheinungsdatum	2024-02-12
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0298112
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Vaccine development: NKT-cell adjuvants in conjugate.

Savage, Paul B

Nature chemical biology

2014 Band 10, Heft 11, Seite(n) 882–883

Mesh-Begriff(e)	Adjuvants, Immunologic ; Carbohydrates/chemistry ; Carbohydrates/immunology ; Epitopes/chemistry ; Epitopes/immunology ; Humans ; Molecular Conformation ; Natural Killer T-Cells/immunology ; Peptides/chemistry ; Peptides/immunology ; Vaccines/chemistry ; Vaccines/immunology
Chemische Substanzen	Adjuvants, Immunologic ; Carbohydrates ; Epitopes ; Peptides ; Vaccines
Sprache	Englisch
Erscheinungsdatum	2014-10-21
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	2202962-X
ISSN	1552-4469 ; 1552-4450
ISSN (online)	1552-4469
ISSN	1552-4450
DOI	10.1038/nchembio.1667
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Antimicrobial Activity of Ceragenins against Vancomycin-Susceptible and -Resistant

Hacioglu, Mayram / Yilmaz, Fatima Nur / Oyardi, Ozlem / Bozkurt Guzel, Cagla / Inan, Nese / Savage, Paul B / Dosler, Sibel

Pharmaceuticals (Basel, Switzerland)

2023 Band 16, Heft 12

Abstract: Ceragenins (CSAs) are a new class of antimicrobial agents designed to mimic the activities of endogenous antimicrobial peptides. In this study, the antibacterial activities of various ceragenins (CSA-13, CSA-44, CSA-90, CSA-131, CSA-138, CSA-142, and CSA- ...

Abstract	Ceragenins (CSAs) are a new class of antimicrobial agents designed to mimic the activities of endogenous antimicrobial peptides. In this study, the antibacterial activities of various ceragenins (CSA-13, CSA-44, CSA-90, CSA-131, CSA-138, CSA-142, and CSA-192), linezolid, and daptomycin were assessed against 50 non-repeated
Sprache	Englisch
Erscheinungsdatum	2023-11-23
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph16121643
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Pandemic coping and COVID-19 preventive behaviors among cancer survivors.

Guidry, Jeanine P D / Miller, Carrie A / Perrin, Paul B / Carlyle, Kellie E / Savage, Matthew W / Sheppard, Vanessa B / Fuemmeler, Bernard F

Patient education and counseling

2023 Band 112, Seite(n) 107716

Abstract: Background: Cancer survivors are at greater risk for COVID-19 complications, emphasizing the importance of adherence to COVID-19 prevention. Active coping mechanisms can help manage pandemic stress but disengaged coping practices can have adverse ... ...

Abstract	Background: Cancer survivors are at greater risk for COVID-19 complications, emphasizing the importance of adherence to COVID-19 prevention. Active coping mechanisms can help manage pandemic stress but disengaged coping practices can have adverse effects. Objectives: 1) Identify differences in COVID-19 coping styles and COVID-19 preventive behaviors among cancer survivors in active treatment, survivors not in treatment, and a comparison group without a cancer history. 2) Exploring variables that may predict adherence to COVID-19 preventative behaviors. Patient involvement & methods: This study used an online survey among two categories of cancer survivors - one group in active treatment and one group no longer in treatment - and one group without a cancer history (N = 897 total). Results and discussion: Cancer survivors in treatment were more likely to utilize both active and disengaged coping (p < .001). This could indicate that the additional COVID-19 strain is making survivors more likely to engage in coping in any way possible. Cancer survivors not in treatment were less likely to report intent to carry out COVID- 19 preventative behaviors compared to the comparison group (p = .009). Providers should understand how survivors may use both coping mechanism types because these coping strategies predict both depression and adherence to COVID-19 preventive behaviors.
Mesh-Begriff(e)	Humans ; COVID-19/epidemiology ; COVID-19/prevention & control ; Cancer Survivors ; Pandemics/prevention & control ; Adaptation, Psychological ; Survivors ; Neoplasms
Sprache	Englisch
Erscheinungsdatum	2023-03-23
Erscheinungsland	Ireland
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	605590-4
ISSN	1873-5134 ; 0738-3991
ISSN (online)	1873-5134
ISSN	0738-3991
DOI	10.1016/j.pec.2023.107716
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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