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AB569, a nontoxic chemical tandem that kills major human pathogenic bacteria
- Source :
- Proc Natl Acad Sci U S A
- Publication Year :
- 2020
-
Abstract
- Antibiotic-resistant superbug bacteria represent a global health problem with no imminent solutions. Here we demonstrate that the combination (termed AB569) of acidified nitrite (A-NO 2 − ) and Na 2 -EDTA (disodium ethylenediaminetetraacetic acid) inhibited all Gram-negative and Gram-positive bacteria tested. AB569 was also efficacious at killing the model organism Pseudomonas aeruginosa in biofilms and in a murine chronic lung infection model. AB569 was not toxic to human cell lines at bactericidal concentrations using a basic viability assay. RNA-Seq analyses upon treatment of P. aeruginosa with AB569 revealed a catastrophic loss of the ability to support core pathways encompassing DNA, RNA, protein, ATP biosynthesis, and iron metabolism. Electrochemical analyses elucidated that AB569 produced more stable SNO proteins, potentially explaining one mechanism of bacterial killing. Our data implicate that AB569 is a safe and effective means to kill pathogenic bacteria, suggesting that simple strategies could be applied with highly advantageous therapeutic/toxicity index ratios to pathogens associated with a myriad of periepithelial infections and related disease scenarios.
- Subjects :
- 0301 basic medicine
Lung Diseases
030106 microbiology
Down-Regulation
medicine.disease_cause
Microbiology
03 medical and health sciences
chemistry.chemical_compound
Mice
Antibiotic resistance
Drug Resistance, Bacterial
medicine
Animals
Viability assay
Edetic Acid
Nitrites
Multidisciplinary
biology
Bacteria
Sodium Nitrite
Pseudomonas aeruginosa
Biofilm
Pathogenic bacteria
Biological Sciences
biology.organism_classification
Anti-Bacterial Agents
Disease Models, Animal
030104 developmental biology
chemistry
Biofilms
Toxicity
DNA
Metabolic Networks and Pathways
Subjects
Details
- ISSN :
- 10916490
- Volume :
- 117
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Accession number :
- edsair.doi.dedup.....fdca1dcb1fd20e5c416cb0d0091e09f3