scholarly journals New Auranofin Analogs with Antibacterial Properties against Burkholderia Clinical Isolates

Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1443
Author(s):  
Dustin Maydaniuk ◽  
Bin Wu ◽  
Dang Truong ◽  
Sajani H. Liyanage ◽  
Andrew M. Hogan ◽  
...  
Keyword(s):  
Burkholderia Cepacia ◽  
Galleria Mellonella ◽  
Therapeutic Potential ◽  
Antibacterial Properties ◽  
Antimicrobial Properties ◽  
Clinical Isolates ◽  
Burkholderia Cepacia Complex ◽  
Model Organisms ◽  
Gram Positive Bacteria ◽  
High Concentrations

Bacteria of the genus Burkholderia include pathogenic Burkholderia mallei, Burkholderia pseudomallei and the Burkholderia cepacia complex (Bcc). These Gram-negative pathogens have intrinsic drug resistance, which makes treatment of infections difficult. Bcc affects individuals with cystic fibrosis (CF) and the species B. cenocepacia is associated with one of the worst clinical outcomes. Following the repurposing of auranofin as an antibacterial against Gram-positive bacteria, we previously synthetized auranofin analogs with activity against Gram-negatives. In this work, we show that two auranofin analogs, MS-40S and MS-40, have antibiotic activity against Burkholderia clinical isolates. The compounds are bactericidal against B. cenocepacia and kill stationary-phase cells and persisters without selecting for multistep resistance. Caenorhabditis elegans and Galleria mellonella tolerated high concentrations of MS-40S and MS-40, demonstrating that these compounds have low toxicity in these model organisms. In summary, we show that MS-40 and MS-40S have antimicrobial properties that warrant further investigations to determine their therapeutic potential against Burkholderia infections.

scholarly journals New auranofin analogs with antibacterial properties against Burkholderia clinical isolates

2021 ◽  
Author(s):  
Dustin Maydaniuk ◽  
Bin Wu ◽  
Dang Truong ◽  
Sajani H. Liyanage ◽  
Andrew M. Hogan ◽  
...  
Keyword(s):  
Burkholderia Cepacia ◽  
Burkholderia Pseudomallei ◽  
Galleria Mellonella ◽  
Antibacterial Properties ◽  
Clinical Isolates ◽  
Model Organisms ◽  
Gram Positive Bacteria ◽  
Low Toxicity ◽  
Intrinsic Drug Resistance ◽  
High Concentrations

AbstractBacteria of the genus Burkholderia include pathogenic Burkholderia mallei, Burkholderia pseudomallei and the Burkholderia cepacia complex (Bcc). These Gram-negative pathogens have intrinsic drug resistance, which makes treatment of infections difficult. Bcc affects individuals with cystic fibrosis (CF) and the species B. cenocepacia is associated with one of the worst clinical outcomes. Following the repurposing of auranofin as an antibacterial against Gram-positive bacteria, we previously synthetized auranofin analogs with activity against Gram-negatives. In this work, we show that two auranofin analogs, MS-40S and MS-40, have antibiotic activity against Burkholderia clinical isolates. The compounds are bactericidal against B. cenocepacia and kill stationary-phase cells and persisters without selecting for multistep resistance. Caenorhabditis elegans and Galleria mellonella tolerated high concentrations of MS-40S and MS-40, demonstrating that these compounds have low toxicity in these model organisms. In summary, we show that MS-40 and MS-40S have the potential to be effective therapeutic options to treat Burkholderia infections.

scholarly journals Swimming Motility in a Longitudinal Collection of Clinical Isolates of Burkholderia cepacia Complex Bacteria from People with Cystic Fibrosis

PLoS ONE ◽  
2014 ◽  
Vol 9 (9) ◽  
pp. e106428 ◽  
Author(s):  
James E. A. Zlosnik ◽  
Paul Y. Mori ◽  
Derek To ◽  
James Leung ◽  
Trevor J. Hird ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Burkholderia Cepacia ◽  
Clinical Isolates ◽  
Burkholderia Cepacia Complex ◽  
Swimming Motility

scholarly journals Burkholderia cepacia Complex Phage-Antibiotic Synergy (PAS): Antibiotics Stimulate Lytic Phage Activity

2014 ◽  
Vol 81 (3) ◽  
pp. 1132-1138 ◽  
Author(s):  
Fatima Kamal ◽  
Jonathan J. Dennis
Keyword(s):  
Burkholderia Cepacia ◽  
Galleria Mellonella ◽  
Burkholderia Cenocepacia ◽  
Burkholderia Cepacia Complex ◽  
Lytic Phage ◽  
Bacterial Killing ◽  
Content Type ◽  
Drug Classes ◽  
Phage Production ◽  
A Chain

ABSTRACTTheBurkholderia cepaciacomplex (Bcc) is a group of at least 18 species of Gram-negative opportunistic pathogens that can cause chronic lung infection in cystic fibrosis (CF) patients. Bcc organisms possess high levels of innate antimicrobial resistance, and alternative therapeutic strategies are urgently needed. One proposed alternative treatment is phage therapy, the therapeutic application of bacterial viruses (or bacteriophages). Recently, some phages have been observed to form larger plaques in the presence of sublethal concentrations of certain antibiotics; this effect has been termed phage-antibiotic synergy (PAS). Those reports suggest that some antibiotics stimulate increased production of phages under certain conditions. The aim of this study is to examine PAS in phages that infectBurkholderia cenocepaciastrains C6433 and K56-2. Bcc phages KS12 and KS14 were tested for PAS, using 6 antibiotics representing 4 different drug classes. Of the antibiotics tested, the most pronounced effects were observed for meropenem, ciprofloxacin, and tetracycline. When grown with subinhibitory concentrations of these three antibiotics, cells developed a chain-like arrangement, an elongated morphology, and a clustered arrangement, respectively. When treated with progressively higher antibiotic concentrations, both the sizes of plaques and phage titers increased, up to a maximum.B. cenocepaciaK56-2-infectedGalleria mellonellalarvae treated with phage KS12 and low-dose meropenem demonstrated increased survival over controls treated with KS12 or antibiotic alone. These results suggest that antibiotics can be combined with phages to stimulate increased phage production and/or activity and thus improve the efficacy of bacterial killing.

scholarly journals 719. Cefiderocol Retains Anti-Biofilm Activity in MDR Gram-Negative Pathogens

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S323-S324
Author(s):  
Christine A Pybus ◽  
David E Greenberg
Keyword(s):  
Burkholderia Cepacia ◽  
Antimicrobial Properties ◽  
Viable Cell ◽  
Multidrug Resistant ◽  
Cell Number ◽  
Burkholderia Cepacia Complex ◽  
Growth Media ◽  
Viable Cell Number ◽  
Gram Negative ◽  
Mueller Hinton

Abstract Background Cefiderocol is a siderophore cephalosporin with potent antibacterial activity against a broad range of Gram-negative pathogens. Microorganisms forming biofilm, e.g., cUTI, utilize bacterial siderophores to access free iron. A siderophore antibiotic may have unique antimicrobial properties in the setting of biofilm. In this study, we compared antimicrobial activity of cefiderocol to comparator antibiotics in well-characterized multi-drug-resistant pathogens. We determined the activity of cefiderocol and comparator antibiotics in the biofilm setting. Methods Minimum inhibitory concentrations (MICs) in Mueller–Hinton II broth (MHII) and iron-depleted cation-adjusted MHII (ID-CAMHB) were determined for cefiderocol and seven comparator antibiotics in multidrug-resistant isolates of P. aeruginosa, Burkholderia cepacia complex (Bcc), Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii. MBEC (minimum biofilm eradication concentration) assays were used to test cefiderocol’s activity in biofilms formed on pegs. Total biofilm biomass and viable cell number were measured. Results The MIC90 of cefiderocol ranged from 0.125 μg/mL (Bcc) to 1 μg/mL (P. aeruginosa) in ID-CAMHB. MIC90 values were consistently lower for cefiderocol in all strains tested compared with other agents (ceftolozane-tazobactam, ceftazidime–avibactam, ceftazidime, pipercallin-tazobactam, imipenem, tobramycin, clarithromycin). Twenty-four hour P. aeruginosa biofilms (strains ATCC 9027, MB640, MB771, MB580A, MB730) were treated every 12 hours with 4 μg/mL of cefiderocol or comparator antibiotics. Cefiderocol treatment displayed a superior reduction in biofilm based on colony counts ( >90%; P < 0.0001 vs. untreated control) compared with comparator drugs (50 to 80% reduction). Crystal violet staining revealed a dose-dependent response of cefiderocol in the reduction of biofilm. Reduction of biofilm was not significantly altered by the growth media that was used; however, P. aeruginosa strains form more biofilm in MHII. Conclusion Cefiderocol effectively reduces biofilm in multidrug-resistant strains of P. aeruginosa and is a potent inhibitor of planktonic growth across a range of Gram-negative medically important pathogens. Disclosures All authors: No reported disclosures.

Granule contents from rat polymorphonuclear leukocytes: antimicrobial properties and characterization

1986 ◽  
Vol 32 (6) ◽  
pp. 498-504 ◽  
Author(s):  
Richard L. Hodinka ◽  
Malcolm C. Modrzakowski
Keyword(s):  
Antibacterial Properties ◽  
Antimicrobial Properties ◽  
Bacterial Cells ◽  
Gram Positive Bacteria ◽  
Properties And Characterization ◽  
Bacterial Mutants ◽  
Killing Action ◽  
Gram Negative Organisms ◽  
Ph Range ◽  
Static Conditions

The nonoxidative antibacterial properties of isolated rat polymorphonuclear leukocyte granule contents were examined using Salmonella typhimurium LT-2 and a series of progressively rough lipopolysaccharide mutants of this strain as target bacteria. The granule extract was most active at 37 °C, with a substantial decrease in activity observed at lower temperatures. Deep rough bacterial mutants were killed best within a pH range of 6–8, while killing of mutants with increased lipopolysaccharide content was most efficient at an acid pH of 5. The activity of the extract was dependent on incubation time but was independent of the number of bacterial cells present in the assay mixture. The killing action of the granule extract was inhibited by the cations Na+, K+, Mg2+, Ca, and Fe2+. The degree of inhibition was dependent on the type and concentration of ion used. Rough mutants grown with aeration to log phase were killed more efficiently than the same mutants grown to stationary phase under static conditions. Also, gram-positive bacteria were more susceptible to the extract than were gram-negative organisms.

scholarly journals Phenolic compounds, antioxidant and antimicrobial properties of the wild cherry (Prunus avium L.) stem

2017 ◽  
pp. 1-13 ◽  
Author(s):  
Zahida Ademovic ◽  
Snjezana Hodzic ◽  
Zarka Halilic-Zahirovic ◽  
Darja Husejnagic ◽  
Jasna Dzananovic ◽  
...  
Keyword(s):  
Phenolic Compounds ◽  
Prunus Avium ◽  
Antibacterial Properties ◽  
Antimicrobial Properties ◽  
Total Phenolic ◽  
Alcoholic Extract ◽  
Aqueous Extracts ◽  
Wild Cherry ◽  
Gram Positive Bacteria ◽  
Prunus Avium L

The aim of this study was to determine the total phenolic content, evaluate antioxidant propertie and antimicrobial potential, and identify phenolic compounds in alcoholic and aqueous extracts of the wild cherry (Prunus avium L.) stems collected in Bosnia and Herzegovina. Alcoholic extracts had higher contents of phenolic and flavonoid components, as well as the antioxidant and ferric reducing antioxidant capacity in comparison to aqueous extracts. All extracts were characterized by HPLC analysis. Furthermore, for the first time, the antimicrobial properties of wild cherry stem extracts were evaluated. Quercetin and (+)-catechin were the main compounds identified in the alcoholic extract, followed by chlorogenic acid and rutin. Quercetin was also the major component detected in aqueous extracts. Besides, alcoholic extract showed better antibacterial properties against Staphylococcus aureus as a representative gram-positive bacteria than infusion, whereas none of the samples showed antibacterial activity against Escherichia coli and fungus Candida albicans.

scholarly journals Antimicrobial Properties of Water-Soluble Polysaccharides and Alcoholic Extracts of Laetiporus Sulphureus (Bull.) Murrill Mycelium and Development of Biotechnology for Its Production in Immobilized Culture on Bacterial Cellulose

2020 ◽  
Vol 65 (1-2) ◽  
pp. 10-14
Author(s):  
I. A. Gavryushina ◽  
T. I. Gromovykh ◽  
N. B. Feldman ◽  
S. V. Lutsenko ◽  
V. I. Ponomarenko ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Bacterial Cellulose ◽  
Synthetic Medium ◽  
Antibacterial Properties ◽  
Antimicrobial Properties ◽  
Water Soluble ◽  
Biologically Active ◽  
Aqueous Extracts ◽  
Gram Positive Bacteria ◽  
Immobilized Culture

The article discusses the development of a new method of producing Laetiporus sulphureus (Bull.) Murrill basidiomycete mycelium immobilized on a bacterial cellulose matrix. Mycelium contains biologically active compounds with antimicrobial activity against Gram-positive bacteria, including resistant staphylococcus. The aim of the work was to obtain immobilized mycelium by co-cultivation of L.sulphureus with the producer of bacterial cellulose Gluconacetobacter hansenii. The authors found that when co-culturing the basidial L.sulphureus strain with the bacterial cellulose producing G.hansenii strain, productivity increases by 3.2 times on H5/1 synthetic medium and by 1.9 times on natural Maltax-10 medium (concentration 5%). The resulting immobilized L.sulphureus mycelium has antibacterial properties; its aqueous extracts contain glucans.

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