scholarly journals Photodynamic Therapy for Acinetobacter baumannii Burn Infections in Mice

2009 ◽  
Vol 53 (9) ◽  
pp. 3929-3934 ◽  
Author(s):  
Tianhong Dai ◽  
George P. Tegos ◽  
Zongshun Lu ◽  
Liyi Huang ◽  
Timur Zhiyentayev ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Acinetobacter Baumannii ◽  
Light Exposure ◽  
Middle Eastern ◽  
Red Light ◽  
Dorsal Surface ◽  
Multidrug Resistant ◽  
Dependent Manner ◽  
Chronic Infections ◽  
Bacterial Luminescence

ABSTRACT Multidrug-resistant Acinetobacter baumannii infections represent a growing problem, especially in traumatic wounds and burns suffered by military personnel injured in Middle Eastern conflicts. Effective treatment with traditional antibiotics can be extremely difficult, and new antimicrobial approaches are being investigated. One of these alternatives to antimicrobials could be the combination of nontoxic photosensitizers (PSs) and visible light, known as photodynamic therapy (PDT). We report on the establishment of a new mouse model of full-thickness thermal burns infected with a bioluminescent derivative of a clinical Iraqi isolate of A. baumannii and its PDT treatment by topical application of a PS produced by the covalent conjugation of chlorin(e6) to polyethylenimine, followed by illumination of the burn surface with red light. Application of 108 A. baumannii cells to the surface of 10-s burns made on the dorsal surface of shaved female BALB/c mice led to chronic infections that lasted, on average, 22 days and that were characterized by a remarkably stable bacterial bioluminescence. PDT carried out on day 0 soon after application of the bacteria gave over 3 log units of loss of bacterial luminescence in a light exposure-dependent manner, while PDT carried out on day 1 and day 2 gave an approximately 1.7-log reduction. The application of PS dissolved in 10% or 20% dimethyl sulfoxide without light gave only a modest reduction in the bacterial luminescence from mouse burns. Some bacterial regrowth in the treated burn was observed but was generally modest. It was also found that PDT did not lead to the inhibition of wound healing. The data suggest that PDT may be an effective new treatment for multidrug-resistant localized A. baumannii infections.

scholarly journals GES Extended-Spectrum β-Lactamases in Acinetobacter baumannii Isolates in Belgium

2010 ◽  
Vol 54 (11) ◽  
pp. 4872-4878 ◽  
Author(s):  
Pierre Bogaerts ◽  
Thierry Naas ◽  
Farid El Garch ◽  
Gaelle Cuzon ◽  
Ariane Deplano ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Western Europe ◽  
Specific Activity ◽  
Restriction Analysis ◽  
Middle Eastern ◽  
Carbapenem Resistance ◽  
Multidrug Resistant ◽  
Single Amino Acid ◽  
Class 1 Integron ◽  
Novel Variant

ABSTRACT During a PCR-based surveillance study of β-lactam resistance, 125 multidrug-resistant (MDR) Acinetobacter baumannii isolates were obtained from 18 hospitals in Belgium from January 2008 to December 2009. Nine GES-positive A. baumannii isolates were detected at 6 Belgian hospitals. DNA sequencing of the bla GES genes identified GES-11, GES-12, and a novel variant GES-14, which differs from GES-11 by a single amino acid substitution (Gly170Ser). All index isolates were travel associated and originated from patients transferred from Turkey (n = 2), Egypt (n = 2), and Palestinian territories (Gaza) (n = 2). A nosocomial outbreak involving three additional patients occurred in a burn unit at a single hospital. No clonal relatedness could be established between the 6 index isolates by pulsed-field gel electrophoresis (PFGE) analysis. Three different alleles (the plasmid-located bla GES-11 and bla GES-12 and a likely chromosomally located novel variant bla GES-14) were detected as part of a class 1 integron, also including the aac6′Ib and dfrA7 genes. Restriction analysis of plasmids suggests a common origin for the plasmids bearing bla GES-11 and bla GES-12. Cloning of the bla GES genes in E scherichia coli identified GES-14 as hydrolyzing imipenem, while GES-12 showed the highest specific activity against ceftazidime. This report highlights the emergence of various bla GES-like genes, especially those conferring carbapenem resistance in A. baumannii and its importation in Western Europe from Middle Eastern countries.

Photodynamic Therapy for Head and Neck Cancer Xenografts in Athymic Mice

1986 ◽  
Vol 95 (5) ◽  
pp. 602-606 ◽  
Author(s):  
James H. Hill ◽  
Randall L. Plant ◽  
David M. Harris ◽  
Randal C. Paniello
Keyword(s):  
Photodynamic Therapy ◽  
Light Intensity ◽  
Head And Neck ◽  
Treatment Time ◽  
Light Exposure ◽  
Red Light ◽  
Human Head ◽  
Athymic Mice ◽  
Squamous Cancer ◽  
Argon Dye Laser

This study examines efficacy and optimal treatment variables of photodynamic therapy (PDT) for human head and neck squamous cancer (HNSC) xenografts in athymic mice. Two and four days after injection of hematoporphyrin derivative (HPD), tumors were illuminated with red light from an argon-dye laser. Sixty-three tumors were treated. With HPD dose and light intensity constant at 7.5 mg/kg and 100 mW/cm2, respectively, the extent of tumor necrosis was strongly dependent on duration of light exposure. There was no substantial difference in results for 30- and 60-minute treatment durations between animals injected with HPD 2 and 4 days before treatment. After 30 minutes treatment time, responses were seen in 8 of 10 mice (2 days post-HPD) and 11 of 12 mice (4 days post-HPD). After 60 minutes treatment time, toxicity was high. We conclude that, in this model, PDT is effective in selective killing of HNSC. For future comparison studies in this model, if the indicated HPD dose and light intensity are used we recommend a 2-day delay after HPD injection and a light exposure duration of 30 minutes

scholarly journals Photodynamic Therapy Is Effective Against Candida auris Biofilms

2021 ◽  
Vol 11 ◽  
Author(s):  
Priyanka S. Bapat ◽  
Clarissa J. Nobile
Keyword(s):  
Photodynamic Therapy ◽  
Fungal Infections ◽  
Red Light ◽  
Green Light ◽  
Multidrug Resistant ◽  
Antifungal Drug ◽  
Candida Auris ◽  
Human Fungal Pathogen ◽  
Drug Classes ◽  
Medical Need

Fungal infections are increasing in prevalence worldwide. The paucity of available antifungal drug classes, combined with the increased occurrence of multidrug resistance in fungi, has led to new clinical challenges in the treatment of fungal infections. Candida auris is a recently emerged multidrug resistant human fungal pathogen that has become a worldwide public health threat. C. auris clinical isolates are often resistant to one or more antifungal drug classes, and thus, there is a high unmet medical need for the development of new therapeutic strategies effective against C. auris. Additionally, C. auris possesses several virulence traits, including the ability to form biofilms, further contributing to its drug resistance, and complicating the treatment of C. auris infections. Here we assessed red, green, and blue visible lights alone and in combination with photosensitizing compounds for their efficacies against C. auris biofilms. We found that (1) blue light inhibited and disrupted C. auris biofilms on its own and that the addition of photosensitizing compounds improved its antibiofilm potential; (2) red light inhibited and disrupted C. auris biofilms, but only in combination with photosensitizing compounds; and (3) green light inhibited C. auris biofilms in combination with photosensitizing compounds, but had no effects on disrupting C. auris biofilms. Taken together, our findings suggest that photodynamic therapy could be an effective non-drug therapeutic strategy against multidrug resistant C. auris biofilm infections.

scholarly journals PCH1 integrates circadian and light-signaling pathways to control photoperiod-responsive growth in Arabidopsis

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
He Huang ◽  
Chan Yul Yoo ◽  
Rebecca Bindbeutel ◽  
Jessica Goldsworthy ◽  
Allison Tielking ◽  
...  
Keyword(s):  
Light Exposure ◽  
Red Light ◽  
Constitutive Expression ◽  
Day Length ◽  
Light Signaling ◽  
Dependent Manner ◽  
Phytochrome B ◽  
Necessary And Sufficient ◽  
New Protein ◽  
Short Days

Plants react to seasonal change in day length through altering physiology and development. Factors that function to harmonize growth with photoperiod are poorly understood. Here we characterize a new protein that associates with both circadian clock and photoreceptor components, named PHOTOPERIODIC CONTROL OF HYPOCOTYL1 (PCH1). pch1 seedlings have overly elongated hypocotyls specifically under short days while constitutive expression of PCH1 shortens hypocotyls independent of day length. PCH1 peaks at dusk, binds phytochrome B (phyB) in a red light-dependent manner, and co-localizes with phyB into photobodies. PCH1 is necessary and sufficient to promote the biogenesis of large photobodies to maintain an active phyB pool after light exposure, potentiating red-light signaling and prolonging memory of prior illumination. Manipulating PCH1 alters PHYTOCHROME INTERACTING FACTOR 4 levels and regulates light-responsive gene expression. Thus, PCH1 is a new factor that regulates photoperiod-responsive growth by integrating the clock with light perception pathways through modulating daily phyB-signaling.

scholarly journals Effective Photodynamic Inactivation of 26 Escherichia coli Strains with Different Antibiotic Susceptibility Profiles: A Planktonic and Biofilm Study

Antibiotics ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 98 ◽  
Author(s):  
Òscar Gulías ◽  
Giselle McKenzie ◽  
Miquel Bayó ◽  
Montserrat Agut ◽  
Santi Nonell
Keyword(s):  
Escherichia Coli ◽  
Methylene Blue ◽  
Photodynamic Therapy ◽  
Reference Strain ◽  
Red Light ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Antimicrobial Photodynamic Therapy ◽  
Strain Atcc

The emergence of multidrug-resistant bacteria is a growing problem and alternative therapies are being sought to effectively address this issue. The aim of this study is to assess a range of Escherichia coli strains’ susceptibility to Methylene Blue-mediated antimicrobial photodynamic therapy and determine if this is affected by their antibiotic-resistance profile. Two reference and twenty-four uropathogenic clinical E. coli strains were used in this study. All were tested in vitro for antimicrobial susceptibility against sixteen antibiotics. Strains underwent photodynamic treatments using the photosensitizer Methylene Blue with red light and tested in both planktonic and biofilm state. It was found that reference strain ATCC 25922 was susceptible to all tested antibiotics whereas reference strain ATCC 35218 showed resistance only to Ampicillin. With the exception of strains number 16 and 22, all of the isolated strains were multidrug-resistant according to the criteria established by the European Centre for Disease Prevention and Control and the Centre for Disease Control and Prevention, where acquired non-susceptibility to at least one agent in three or more antimicrobial categories is outlined. Photodynamic therapy induced more than 3 log10 colony-forming units’ reduction to all strains in planktonic state. Whereas when tested in biofilm state, two and a half times the original dose of methylene blue was necessary to cause a 3 log10 antimicrobial effect. There were statistically significant differences in susceptibility among the strains tested in both the planktonic and biofilm experiments. Nevertheless, antimicrobial photodynamic therapy could inactivate all multidrug-resistant strains in the planktonic and biofilm state.

Photodynamic Therapy with 5-Aminolevulinic Acid Induces Apoptosis and Caspase Activation in Malignant T Cells

2001 ◽  
Vol 5 (1) ◽  
pp. 8-13 ◽  
Author(s):  
Faten Gad ◽  
Gilles Viau ◽  
Michele Bousbira ◽  
Richard Bertrand ◽  
Robert Bissonnette
Keyword(s):  
Photodynamic Therapy ◽  
Dna Fragmentation ◽  
Caspase 3 ◽  
Aminolevulinic Acid ◽  
Light Exposure ◽  
Red Light ◽  
Jurkat Cells ◽  
Caspase Activation ◽  
Light Fluence ◽  
Malignant T Cells

Background: Preliminary studies have suggested that photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) can improve psoriasis and mycosis fungoides, two diseases where normal or malignant T cells play a central role. Objectives: To determine if ALA-PDT induces apoptosis and caspase activation in Jurkat cells, a malignant T-cell line. Methods: Jurkat cells were incubated with ALA in the presence of [14C]-thymidine followed by red light exposure. DNA fragmentation was measured 24 hours later with a DNA elution assay. The influence on DNA fragmentation of ALA concentration, time between ALA addition and light exposure, as well as light fluence were studied. The occurrence of oligonucleosome-sized DNA fragmentation was also studied with DNA electrophoresis. Caspase-3-like activity was monitored by measuring Ac-DEVD-AMC hydrolysis. Results: DNA fragmentation as high as 88% was observed 24 hours after ALA-PDT. The percentage of DNA fragmentation increased with increasing doses of ALA, red light fluence, as well as longer incubation time with ALA. DNA fragmentation was observed as early as 3 hours after ALA-PDT. The presence of apoptosis after ALA-PDT was confirmed by DNA electrophoresis. An increase in caspase-3-like activities was detected following ALA-PDT. Conclusion: ALA-PDT induces apoptosis and caspase-3-like activation in Jurkat cells.

scholarly journals 1073. Sulbactam-Durlobactam Has Potent Activity Against Multidrug-Resistant Acinetobacter baumannii Clinical Isolates From Thai Patients With Chronic Infections

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S628-S629
Author(s):  
Dhammika Leshan Wannigama ◽  
Paul G Higgins ◽  
Cameron Hurst ◽  
Shuichi Abe ◽  
Parichart Hongsing ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Therapeutic Option ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Multi Drug Resistance ◽  
Chronic Infections ◽  
Novel Treatments ◽  
Medical Wards ◽  
Considerable Morbidity

Abstract Background Due to the increase in multi-drug resistance (MDR) of Acinetobacter baumannii chronic infections with accompanying considerable morbidity and mortality, it is imperative to find effective novel treatments. Durlobactam (DUR) is a potent broad-spectrum inhibitor of Ambler classes A, C and D serine β-lactamases that effectively restores sulbactam (SUL) activity against MDR A.baumannii isolates. SUL-DUR is currently in late-stage development for the treatment of infections caused by Acinetobacter spp., including drug resistant isolates. In this study, we sought to evaluate potency of SUL-DUR against MDR A. baumannii isolates collected from Thai patients with chronic infections. Methods Non-duplicative clinical strains were isolated during 2016–2019 from 200 chronically infected patients in different medical wards with a variety of different infections at King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Susceptibility testing of SUL-DUR and comparator agents was performed according to CLSI guidelines. SUL-DUR was also tested on a background of imipenem (IPM) therapy (SUL-IPM titrated at a 1:1 ratio plus DUR fixed at 4 mg/L). Data analysis was performed using CLSI and EUCAST breakpoint criteria where available. Results This collection of isolates was 92% sulbactam-resistant (using a breakpoint of 4 mg/L), 91% carbapenem-resistant, 74% amikacin resistant and 8% colistin resistant. In contrast, the SUL-DUR MIC90 was 4 mg/L compared with 64 mg/L for sulbactam alone. SUL-DUR was equally potent across antibiotic-resistant subsets. Only 6 isolates (3%) had SUL-DUR MIC values >4 mg/L. Interestingly, addition of imipenem to SUL-DUR showed similar potency as SUL-DUR alone, with an MIC90 of 2 mg/L. Conclusion SUL-DUR showed potent in vitro activity against contemporary clinical isolates from a hospital in Bangkok, Thailand. If successfully developed, SUL-DUR may be an important new therapeutic option for the treatment of MDR Acinetobacter infections. Disclosures Alita Miller, PhD, Entasis Therapeutics (Employee)

scholarly journals K2 Capsule Depolymerase Is Highly Stable, Is Refractory to Resistance, and Protects Larvae and Mice from Acinetobacter baumannii Sepsis

2019 ◽  
Vol 85 (17) ◽  
Author(s):  
Hugo Oliveira ◽  
Ana Mendes ◽  
Alexandra G. Fraga ◽  
Alice Ferreira ◽  
Andreia I. Pimenta ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Acinetobacter Baumannii ◽  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Host Immune System ◽  
Dependent Manner ◽  
Bacterial Cells ◽  
Capsular Type ◽  
Nosocomial Pathogen ◽  
Content Type

ABSTRACT Acinetobacter baumannii is emerging as a major nosocomial pathogen in intensive care units. The bacterial capsules are considered major virulence factors, and the particular A. baumannii capsular type K2 has been associated with high antibiotic resistance. In this study, we identified a K2 capsule-specific depolymerase in a bacteriophage tail spike C terminus, a fragment that was heterologously expressed, and its antivirulence properties were assessed by in vivo experiments. The K2 depolymerase is active under a broad range of environmental conditions and is highly thermostable, with a melting point (Tm) at 67°C. In the caterpillar larva model, the K2 depolymerase protects larvae from bacterial infections, using either pretreatments or with single-enzyme injection after bacterial challenge, in a dose-dependent manner. In a mouse sepsis model, a single K2 depolymerase intraperitoneal injection of 50 μg is able to protect 60% of mice from an otherwise deadly infection, with a significant reduction in the proinflammatory cytokine profile. We showed that the enzyme makes bacterial cells fully susceptible to the host complement system killing effect. Moreover, the K2 depolymerase is highly refractory to resistance development, which makes these bacteriophage-derived capsular depolymerases useful antivirulence agents against multidrug-resistant A. baumannii infections. IMPORTANCE Acinetobacter baumannii is an important nosocomial pathogen resistant to many, and sometimes all, antibiotics. The A. baumannii K2 capsular type has been associated with elevated antibiotic resistance. The capsular depolymerase characterized here fits the new trend of alternative antibacterial agents needed against multidrug-resistant pathogens. They are highly specific, stable, and refractory to resistance, as they do not kill bacteria per se; instead, they remove bacterial surface polysaccharides, which diminish the bacterial virulence and expose them to the host immune system.

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