AB569, a non-toxic combination of acidified nitrite and EDTA, is effective at killing the notorious Iraq Afghanistan combat wound pathogens, multi-drug resistant Acinetobacter baumannii and Acinetobacter spp
Amy L Bogue, Warunya Panmanee, Cameron T McDaniel, Joel E Mortensen, Edwin Kamau, Luis A Actis, Jay A Johannigman, Michael J Schurr, Latha Satish, Nalinikanth Kotagiri, Daniel J Hassett
Multi-drug resistant (MDR) Acinetobacter baumannii (Ab) and Acinetobacter spp. present monumental global health challenges. These organisms represent model Gram-negative pathogens with known antibiotic resistance and biofilm-forming properties. Herein, a novel, nontoxic biocide, AB569, consisting of acidified nitrite (A-NO2-) and ethylenediaminetetraacetic acid (EDTA), demonstrated bactericidal activity against all Ab and Acinetobacter spp. strains, respectively. Average fractional inhibitory concentrations (FICs) of 0.25 mM EDTA plus 4 mM A-NO2- were observed across several clinical reference and multiple combat wound isolates from the Iraq/Afghanistan wars. Importantly, toxicity testing on human dermal fibroblasts ...
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 ...