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Author Mihu, M.R.; Cabral, V.; Pattabhi, R.; Tar, M.T.; Davies, K.P.; Friedman, A.J.; Martinez, L.R.; Nosanchuk, J.D.
Title Sustained Nitric Oxide-Releasing Nanoparticles Interfere with Methicillin-Resistant Staphylococcus aureus Adhesion and Biofilm Formation in a Rat Central Venous Catheter Model Type Journal Article
Year 2017 Publication Antimicrobial Agents and Chemotherapy Abbreviated Journal Antimicrob Agents Chemother
Volume 61 Issue 1 Pages
Keywords Animals; Anti-Bacterial Agents/chemistry/*pharmacology; Bacterial Adhesion/drug effects; Biofilms/*drug effects/growth & development; Catheter-Related Infections/*drug therapy/microbiology; Central Venous Catheters; Chitosan/chemistry/pharmacology; Delayed-Action Preparations; Disease Models, Animal; Female; Glucose/chemistry; Humans; Methicillin-Resistant Staphylococcus aureus/*drug effects/growth & development/ultrastructure; Nanoparticles/*administration & dosage/chemistry; Nitric Oxide/chemical synthesis/*pharmacology; Oxidation-Reduction; Plankton/drug effects/growth & development; Rats; Rats, Sprague-Dawley; Sodium Nitrite/chemistry; Staphylococcal Infections/*drug therapy/microbiology; Staphylococcus aureus; antimicrobials; biofilms; nanoparticles; nitric oxide
Abstract Staphylococcus aureus is frequently isolated in the setting of infections of indwelling medical devices, which are mediated by the microbe's ability to form biofilms on a variety of surfaces. Biofilm-embedded bacteria are more resistant to antimicrobial agents than their planktonic counterparts and often cause chronic infections and sepsis, particularly in patients with prolonged hospitalizations. In this study, we demonstrate that sustained nitric oxide-releasing nanoparticles (NO-np) interfere with S. aureus adhesion and prevent biofilm formation on a rat central venous catheter (CVC) model of infection. Confocal and scanning electron microscopy showed that NO-np-treated staphylococcal biofilms displayed considerably reduced thicknesses and bacterial numbers compared to those of control biofilms in vitro and in vivo, respectively. Although both phenotypes, planktonic and biofilm-associated staphylococci, of multiple clinical strains were susceptible to NO-np, bacteria within biofilms were more resistant to killing than their planktonic counterparts. Furthermore, chitosan, a biopolymer found in the exoskeleton of crustaceans and structurally integrated into the nanoparticles, seems to add considerable antimicrobial activity to the technology. Our findings suggest promising development and translational potential of NO-np for use as a prophylactic or therapeutic against bacterial biofilms on CVCs and other medical devices.
Address (up) Department of Microbiology and Immunology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, USA
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0066-4804 ISBN Medium
Area Expedition Conference
Notes PMID:27821454 Approved no
Call Number ref @ user @ Serial 100161
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Author Zapotoczna, M.; Forde, E.; Hogan, S.; Humphreys, H.; O'Gara, J.P.; Fitzgerald-Hughes, D.; Devocelle, M.; O'Neill, E.
Title Eradication of Staphylococcus aureus Biofilm Infections Using Synthetic Antimicrobial Peptides Type Journal Article
Year 2017 Publication The Journal of Infectious Diseases Abbreviated Journal J Infect Dis
Volume 215 Issue 6 Pages 975-983
Keywords Animals; Anti-Bacterial Agents/*pharmacology; Biofilms/*drug effects; Catheter-Related Infections/*drug therapy; Cytokines/blood; Disease Models, Animal; Humans; Methicillin-Resistant Staphylococcus aureus/*drug effects; Microbial Sensitivity Tests; Peptides/*pharmacology; Peptides, Cyclic/pharmacology; Rats; Rats, Sprague-Dawley; Staphylococcal Infections/*drug therapy; Vancomycin/administration & dosage; *Staphylococcus aureus; *antimicrobial peptides (AMPs); *biofilm; *catheter lock solution (CLS)
Abstract Here, we demonstrate that antimicrobial peptides (AMPs) are an effective antibiofilm treatment when applied as catheter lock solutions (CLSs) against S. aureus biofilm infections. The activity of synthetic AMPs (Bac8c, HB43, P18, Omiganan, WMR, Ranalexin, and Polyphemusin) was measured against early and mature biofilms produced by methicillin-resistant S. aureus and methicillin-susceptible S. aureus isolates from patients with device-related infections grown under in vivo-relevant biofilm conditions. The cytotoxic and hemolytic activities of the AMPs against human cells and their immunomodulatory potential in human blood were also characterized. The D-Bac8c2,5Leu variant emerged as the most effective AMP during in vitro studies and was also highly effective in eradicating S. aureus biofilm infection when used in a CLS rat central venous catheter infection model. These data support the potential use of D-Bac8c2,5Leu, alone or in combination with other AMPs, in the treatment of S. aureus intravenous catheter infections.
Address (up) Department of Microbiology, School of Natural Sciences, National University of Ireland, Galway, Ireland
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0022-1899 ISBN Medium
Area Expedition Conference
Notes PMID:28453851 Approved no
Call Number ref @ user @ Serial 99511
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Author Zapotoczna, M.; Forde, E.; Hogan, S.; Humphreys, H.; O'Gara, J.P.; Fitzgerald-Hughes, D.; Devocelle, M.; O'Neill, E.
Title Eradication of Staphylococcus aureus Biofilm Infections Using Synthetic Antimicrobial Peptides Type Journal Article
Year 2017 Publication The Journal of Infectious Diseases Abbreviated Journal J Infect Dis
Volume 215 Issue 6 Pages 975-983
Keywords Animals; Anti-Bacterial Agents/*pharmacology; Biofilms/*drug effects; Catheter-Related Infections/*drug therapy; Cytokines/blood; Disease Models, Animal; Humans; Methicillin-Resistant Staphylococcus aureus/*drug effects; Microbial Sensitivity Tests; Peptides/*pharmacology; Peptides, Cyclic/pharmacology; Rats; Rats, Sprague-Dawley; Staphylococcal Infections/*drug therapy; Vancomycin/administration & dosage; *Staphylococcus aureus; *antimicrobial peptides (AMPs); *biofilm; *catheter lock solution (CLS)
Abstract Here, we demonstrate that antimicrobial peptides (AMPs) are an effective antibiofilm treatment when applied as catheter lock solutions (CLSs) against S. aureus biofilm infections. The activity of synthetic AMPs (Bac8c, HB43, P18, Omiganan, WMR, Ranalexin, and Polyphemusin) was measured against early and mature biofilms produced by methicillin-resistant S. aureus and methicillin-susceptible S. aureus isolates from patients with device-related infections grown under in vivo-relevant biofilm conditions. The cytotoxic and hemolytic activities of the AMPs against human cells and their immunomodulatory potential in human blood were also characterized. The D-Bac8c2,5Leu variant emerged as the most effective AMP during in vitro studies and was also highly effective in eradicating S. aureus biofilm infection when used in a CLS rat central venous catheter infection model. These data support the potential use of D-Bac8c2,5Leu, alone or in combination with other AMPs, in the treatment of S. aureus intravenous catheter infections.
Address (up) Department of Microbiology, School of Natural Sciences, National University of Ireland, Galway, Ireland
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0022-1899 ISBN Medium
Area Expedition Conference
Notes PMID:28453851 Approved no
Call Number ref @ user @ Serial 100541
Permanent link to this record
 

 
Author Sullivan, K.E.; Rojas, K.; Cerione, R.A.; Nakano, I.; Wilson, K.F.
Title The stem cell/cancer stem cell marker ALDH1A3 regulates the expression of the survival factor tissue transglutaminase, in mesenchymal glioma stem cells Type Journal Article
Year 2017 Publication Oncotarget Abbreviated Journal Oncotarget
Volume 8 Issue 14 Pages 22325-22343
Keywords Aldehyde Oxidoreductases/genetics/*metabolism; Biomarkers, Tumor/metabolism; Brain Neoplasms/genetics/*metabolism; Cell Line, Tumor; Cell Proliferation; Cell Survival; Dacarbazine/analogs & derivatives/pharmacology; GTP-Binding Proteins/genetics/*metabolism; Gene Expression Regulation, Neoplastic; Glioma/genetics/*metabolism; Humans; Mesenchymal Stromal Cells/*physiology; Neoplastic Stem Cells/*physiology; RNA, Small Interfering/genetics; Stem Cells/*physiology; Transglutaminases/genetics/*metabolism; Tretinoin/metabolism; Up-Regulation; aldehyde dehydrogenase; cancer stem cells; glioblastoma; retinoic acid; tissue transglutaminase
Abstract Tissue transglutaminase (tTG), a dual-function enzyme with GTP-binding and acyltransferase activities, has been implicated in the survival and chemotherapy resistance of aggressive cancer cells and cancer stem cells, including glioma stem cells (GSCs). Using a model system comprising two distinct subtypes of GSCs referred to as proneural (PN) and mesenchymal (MES), we find that the phenotypically aggressive and radiation therapy-resistant MES GSCs exclusively express tTG relative to PN GSCs. As such, the self-renewal, proliferation, and survival of these cells was sensitive to treatment with tTG inhibitors, with a benefit being observed when combined with the standard of care for high grade gliomas (i.e. radiation or temozolomide). Efforts to understand the molecular drivers of tTG expression in MES GSCs revealed an unexpected link between tTG and a common marker for stem cells and cancer stem cells, Aldehyde dehydrogenase 1A3 (ALDH1A3). ALDH1A3, as well as other members of the ALDH1 subfamily, can function in cells as a retinaldehyde dehydrogenase to generate retinoic acid (RA) from retinal. We show that the enzymatic activity of ALDH1A3 and its product, RA, are necessary for the observed expression of tTG in MES GSCs. Additionally, the ectopic expression of ALDH1A3 in PN GSCs is sufficient to induce the expression of tTG in these cells, further demonstrating a causal link between ALDH1A3 and tTG. Together, these findings ascribe a novel function for ALDH1A3 in an aggressive GSC phenotype via the up-regulation of tTG, and suggest the potential for a similar role by ALDH1 family members across cancer types.
Address (up) Department of Molecular Medicine, Cornell University, Ithaca, NY, USA
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1949-2553 ISBN Medium
Area Expedition Conference
Notes PMID:28423611 Approved no
Call Number ref @ user @ Serial 96595
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Author Saleh, H.M.; Tawfik, M.M.; Abouellail, H.
Title Prospective, randomized study of long-term hemodialysis catheter removal versus guidewire exchange to treat catheter-related bloodstream infection Type Randomized Controlled Trial
Year 2017 Publication Journal of Vascular Surgery Abbreviated Journal J Vasc Surg
Volume 66 Issue 5 Pages 1427-1431.e1
Keywords Aged; Anti-Bacterial Agents/therapeutic use; Catheter-Related Infections/blood/diagnosis/microbiology/*therapy; Catheterization, Central Venous/*adverse effects/*instrumentation; Catheters, Indwelling/*adverse effects; Central Venous Catheters/*adverse effects; *Device Removal/adverse effects; Disease-Free Survival; Egypt; Equipment Design; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Prospective Studies; Renal Dialysis; Risk Factors; Time Factors; Treatment Outcome
Abstract BACKGROUND: Long-term (tunneled cuffed) hemodialysis catheters are frequently used vascular access in renal failure patients. Catheter-related bloodstream infection (CRBSI) is a common complication of long-term hemodialysis catheters, with severe morbidities and high risk of mortality. Management of CRBSI by systemic antibiotics while keeping the catheter in place is not effective. Among the different modalities of CRBSI management are catheter removal (CR) and guidewire exchange (GE) of the catheter. The aim of this study was to compare the clinical outcome of CRBSI treated with two different strategies: GE vs CR with new catheter insertion 3 to 7 days later. METHODS: This prospective randomized study analyzed the outcomes of all cases of long-term hemodialysis CRBSI during a 5-year period. The catheter infection-free survival time was analyzed in the two groups of patients (GE group, 339 patients; CR group, 339 patients). Three weeks of systemic antibiotic therapy was used according to culture in both groups. The catheter infection-free survival was analyzed using Kaplan-Meier analysis. RESULTS: No statistically significant difference was found in catheter infection-free survival time for GE and CR groups (P = .69), which is not affected by age, sex, presence of diabetes mellitus, or type of causative organism. CONCLUSIONS: Our study did not demonstrate a difference in the clinical outcome of CRBSI treated with GE or CR with new catheter insertion 3 to 7 days later. However, guidewire catheter exchange saves veins for future access, reduces the cost and number of procedures, and avoids complications of new venipuncture.
Address (up) Department of Nephrology, Ain Shams University, El Demerdash Hospital, Cairo, Egypt
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0741-5214 ISBN Medium
Area Expedition Conference
Notes PMID:28822660 Approved no
Call Number ref @ user @ Serial 99317
Permanent link to this record