A Novel Bactericidal Drug Effective Against Gram-Positive and Gram-Negative Pathogenic Bacteria: Easy as AB569
Daniel J. Hassett and Thomas J. Meyer
Global antibiotic resistance, driven by intensive antibiotic exposure/abuse, constitutes a serious challenge to all health care, particularly in an era when new antimicrobial development has slowed to a trickle. Recently, we published work demonstrating the discovery and partial mechanism of action of a novel bactericidal agent that is effective against both gram-positive and gram-negative multidrug-resistant bacteria. This drug, called AB569, consists of acidified nitrite (A-NO2−) and EDTA, of which there is no mechanism of resistance. Using both chemistry-, genetic-, and bioinformatics-based techniques, we first discovered that AB569 was able to generate bactericidal levels of nitric oxide (NO), while the EDTA component stabilized S-nitrosyl thiols, thereby furthering NO and downstream reactive ...
Jennifer J. Rahna,b,d, Xueqing Luna,b,d, Selina K. Jorchc,e, Xiaoguang Haoa,b,d, Chitra Venugopalg, Parvez Vorag, Bo Young Ahna,b,d, Liane Babesa,b,d, Mana M. Alshehria,b,d,1, J. Gregory Cairncrossa,b,f, Sheila K. Singhg, Paul Kubesc,e, Donna L. Sengera,b,d,∗∗, Stephen M. Robbinsa,b,d,∗
a Arnie Charbonneau Cancer Institute, University of Calgary
b Clark H. Smith Brain Tumour Centre, University of Calgary
c Calvin, Phoebe & Joan Snyder Institute For Chronic Diseases, University of Calgary
d Departments of Oncology, University of Calgary
e Physiology and Pharmacology, University of Calgary
f Clinical Neurosciences, University of Calgary
g Department of Surgery, McMaster Children's Hospital, And McMaster Stem Cell and Cancer Research Institute, McMaster University
Despite extensive molecular characterization, human glioblastoma remains a fatal disease with ...
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, Fiona S. L. Brinkman, Robert E. W. Hancock, Thomas J. Meyer, and Daniel J. Hassett
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 ...