Bisphosphocins: novel antimicrobials for enhanced killing of drug-resistant and biofilm-forming bacteria.
Identifieur interne : 000810 ( Main/Merge ); précédent : 000809; suivant : 000811Bisphosphocins: novel antimicrobials for enhanced killing of drug-resistant and biofilm-forming bacteria.
Auteurs : Jonathan P. Wong [Canada] ; Paul Ditullio [États-Unis] ; Steve Parkinson [États-Unis]Source :
- Future microbiology [ 1746-0921 ] ; 2015.
English descriptors
- KwdEn :
- Animals, Anti-Bacterial Agents (administration & dosage), Anti-Bacterial Agents (adverse effects), Anti-Bacterial Agents (chemistry), Anti-Bacterial Agents (pharmacology), Bacteria (drug effects), Bacteria (growth & development), Bacterial Infections (drug therapy), Biofilms (drug effects), Biofilms (growth & development), Cell Membrane (drug effects), Disease Models, Animal, Drug Evaluation, Preclinical, Drug Resistance, Multiple, Bacterial, Membrane Potentials (drug effects), Microbial Viability (drug effects).
- MESH :
- chemical , administration & dosage : Anti-Bacterial Agents.
- chemical , adverse effects : Anti-Bacterial Agents.
- chemical , chemistry : Anti-Bacterial Agents.
- chemical , pharmacology : Anti-Bacterial Agents.
- drug effects : Bacteria, Biofilms, Cell Membrane, Membrane Potentials, Microbial Viability.
- drug therapy : Bacterial Infections.
- growth & development : Bacteria, Biofilms.
- Animals, Disease Models, Animal, Drug Evaluation, Preclinical, Drug Resistance, Multiple, Bacterial.
Abstract
The global prevalence of antibiotic resistance and the threat posed by drug-resistant superbugs are a leading challenge confronting modern medicine in the 21st century. However, the progress on the development of novel antibiotics to combat this problem is severely lagging. A more concerted effort to develop novel therapeutic agents with robust activity and unique mechanisms of action will be needed to overcome the problem of drug resistance. Furthermore, biofilm forming bacteria are known to be increasingly resistant to the actions of antibiotics and are a leading cause of mortality or morbidity in nosocomial infections. Bisphosphocins (also scientifically known as nubiotics) are novel small protonated deoxynucleotide molecules, and exert their antibacterial activity by depolarization of the bacterial cell membrane, causing bacterial cell death. Bisphosphocins may represent an effective weapon against antibiotic-resistant and biofilm-forming pathogenic bacteria. Preclinical efficacy studies in animals have shown that the compounds are safe and, efficacious against various bacterial infections, including drug-resistant pathogens. In vitro biochemical analysis confirmed that the bactericidal activity of bisphosphocins is mediated by depolarization of the bacterial cell membrane, and these compounds are better able to penetrate through bacterial biofilm and kill the biofilm encased bacteria. This article will cover the structure, mode of action, safety, efficacy and the current state of development of bisphosphocins. Together, the information presented here will present a strong case for bisphosphocins to be considered for use as new weapons to complement the existing arsenal of antimicrobial drugs and as a first line defence against drug-resistant and biofilm-forming bacteria.
DOI: 10.2217/fmb.15.70
PubMed: 26597426
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pubmed:26597426Le document en format XML
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<front><div type="abstract" xml:lang="en">The global prevalence of antibiotic resistance and the threat posed by drug-resistant superbugs are a leading challenge confronting modern medicine in the 21st century. However, the progress on the development of novel antibiotics to combat this problem is severely lagging. A more concerted effort to develop novel therapeutic agents with robust activity and unique mechanisms of action will be needed to overcome the problem of drug resistance. Furthermore, biofilm forming bacteria are known to be increasingly resistant to the actions of antibiotics and are a leading cause of mortality or morbidity in nosocomial infections. Bisphosphocins (also scientifically known as nubiotics) are novel small protonated deoxynucleotide molecules, and exert their antibacterial activity by depolarization of the bacterial cell membrane, causing bacterial cell death. Bisphosphocins may represent an effective weapon against antibiotic-resistant and biofilm-forming pathogenic bacteria. Preclinical efficacy studies in animals have shown that the compounds are safe and, efficacious against various bacterial infections, including drug-resistant pathogens. In vitro biochemical analysis confirmed that the bactericidal activity of bisphosphocins is mediated by depolarization of the bacterial cell membrane, and these compounds are better able to penetrate through bacterial biofilm and kill the biofilm encased bacteria. This article will cover the structure, mode of action, safety, efficacy and the current state of development of bisphosphocins. Together, the information presented here will present a strong case for bisphosphocins to be considered for use as new weapons to complement the existing arsenal of antimicrobial drugs and as a first line defence against drug-resistant and biofilm-forming bacteria.</div>
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