AB569, A Nontoxic Chemical Tandem That Kills Major Human Pathogenic Bacteria

Antibiotic-resistant “super-bug” bacteria represent a global health problem with no imminent solutions. Here, we demonstrate that AB569 (acidified nitrite (A-NO2-) and Na2-EDTA) killed all Gram-negative and Gram-positive bacteria tested. AB569 was also efficacious at killing the model organism P. aeruginosa in biofilms and in a murine chronic lung infection model. AB569 was not toxic to human cell lines at bactericidal concentrations. 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 peri-epithelial infections and related disease scenarios. Overall design: 11 total samples. 3 treatment conditions and 1 control condition. 3 biological replicates for all conditions except for the first treatment condition (NaNO2), where there are only 2 biological replicates.