Dataset Information

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

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.

SUBMITTER: McDaniel CT

PROVIDER: S-EPMC7060718 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

McDaniel Cameron T CT Panmanee Warunya W Winsor Geoffrey L GL Gill Erin E Bertelli Claire C Schurr Michael J MJ Dongare Prateek P Paul Andrew T AT Ko Seung-Hyun B SB Lau Gee W GW Dasgupta Nupur N Bogue Amy L AL Miller William E WE Mortensen Joel E JE Haslam David B DB Dexheimer Phillip P Muruve Daniel A DA Aronow Bruce J BJ Forbes Malcolm D E MDE Danilczuk Marek M Brinkman Fiona S L FSL Hancock Robert E W REW Meyer Thomas J TJ Hassett Daniel J DJ

Proceedings of the National Academy of Sciences of the United States of America 20200218 9

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 to ...[more]

PMID: 32071223

Similar Datasets

Project description:Evolution has led to the expansion of survival strategies in pathogens including bacteria and emergence of drug resistant strains proved to be a major global threat. Vaccination is a promising strategy to protect human population. Reverse vaccinology is a more robust vaccine development approach especially with the availability of large-scale sequencing data and rapidly dropping cost of the techniques for acquiring such data from various organisms. The present study implements an immunoinformatic approach for screening the possible antigenic proteins among various pathogenic bacteria to systemically arrive at epitope-based vaccine candidates against 14 pathogenic bacteria. Thousand four hundred and fifty nine virulence factors and Five hundred and forty six products of essential genes were appraised as target proteins to predict potential epitopes with potential to stimulate different arms of the immune system. To address the self-tolerance, self-epitopes were identified by mapping on 1000 human proteome and were removed. Our analysis revealed that 21proteins from 5 bacterial species were found as virulent as well as essential to their survival, proved to be most suitable vaccine target against these species. In addition to the prediction of MHC-II binders, B cell and T cell epitopes as well as adjuvants individually from proteins of all 14 bacterial species, a stringent criteria lead us to identify 252 unique epitopes, which are predicted to be T-cell epitopes, B-cell epitopes, MHC II binders and Vaccine Adjuvants. In order to provide service to scientific community, we developed a web server VacTarBac for designing of vaccines against above species of bacteria. This platform integrates a number of tools that includes visualization tools to present antigenicity/epitopes density on an antigenic sequence. These tools will help users to identify most promiscuous vaccine candidates in a pathogenic antigen. This server VacTarBac is available from URL (http://webs.iiitd.edu.in/raghava/vactarbac/).

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets