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| Status |
Public on Feb 18, 2020 |
| Title |
AB569, A Nontoxic Chemical Tandem That Kills Major Human Pathogenic Bacteria |
| Organism |
Pseudomonas aeruginosa PAO1 |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
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| 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.
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| Web link |
https://www.pnas.org/content/117/9/4921.long
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| Contributor(s) |
McDaniel C, Panmanee W, Winsor GL, Gill EE, Bertelli C, Schurr MJ, Dongare P, Paul AT, Ko SB, Lau GW, Dasgupta N, Bogue AL, Miller WE, Mortensen JE, Haslam DB, Dexheimer P, Muruve DA, Aronow BJ, Forbes ME, Danilczuk M, Brinkman FL, Hancock RW, Meyer TJ, Hassett DJ |
| Citation(s) |
32071223 |
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| Submission date |
Dec 26, 2019 |
| Last update date |
May 26, 2020 |
| Contact name |
Erin Gill |
| E-mail(s) |
[email protected]
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| Organization name |
University of British Columbia
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| Street address |
2259 Lower Mall
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| City |
Vancouver |
| State/province |
British Columbia |
| ZIP/Postal code |
V6T 1Z4 |
| Country |
Canada |
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| Platforms (1) |
| GPL18782 |
Illumina HiSeq 2500 (Pseudomonas aeruginosa PAO1) |
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| Samples (11)
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| Relations |
| BioProject |
PRJNA597754 |
| SRA |
SRP238832 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE142611_RAW.tar |
250.0 Kb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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