AB569, a nontoxic chemical tandem that kills major human pathogenic bacteria

Cameron T. McDaniel, Warunya Panmanee, Geoffrey L. Winsor, Erin Gill, Claire Bertelli, Michael J. Schurr, Prateek Dongare, Andrew T. Paul, Seung Hyun B. Ko, Gee W. Lau, Nupur Dasgupta, Amy L. Bogue, William E. Miller, Joel E. Mortensen, David B. Haslam, Phillip Dexheimer, Daniel A. Muruve, Bruce J. Aronow, Malcolm D.E. Forbes, Marek Danilczuk & 4 others Fiona S.L. Brinkman, Robert Hancock, Thomas J. Meyer, Daniel J. Hassett

Research output: Contribution to journalArticle

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-NO2 ) and Na2-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.

LanguageEnglish
Pages4921-4930
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number9
DOIs
Publication statusPublished - 3 Mar 2020

Keywords

  • Antibiotic resistance
  • Bactericidal
  • Biofilm
  • EDTA
  • Sodium nitrite

ASJC Scopus subject areas

  • General

Cite this

McDaniel, C. T., Panmanee, W., Winsor, G. L., Gill, E., Bertelli, C., Schurr, M. J., ... Hassett, D. J. (2020). AB569, a nontoxic chemical tandem that kills major human pathogenic bacteria. Proceedings of the National Academy of Sciences of the United States of America, 117(9), 4921-4930. https://doi.org/10.1073/pnas.1911927117