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Tytuł pozycji:

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.

Tytuł:
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.
Autorzy:
Bogue AL; Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, Cincinnati, OH, United States of America.; Wright-Patterson Air Force Base, Dayton (Wright-Patterson Air Force Base), Dayton, OH, United States of America.
Panmanee W; Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, Cincinnati, OH, United States of America.
McDaniel CT; Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, Cincinnati, OH, United States of America.
Mortensen JE; Diagnostic Infectious Disease Testing Laboratory and Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States of America.
Kamau E; Walter Reed National Military Medical Center (WRNMMC), Bethesda, MD, United States of America.
Actis LA; Department of Microbiology, Miami University, Oxford, OH, United States of America.
Johannigman JA; U.S. Army Institute of Surgical Research, San Antonio, TX, United States of America.
Schurr MJ; Department of Immunology and Microbiology, University of Colorado Anschutz School of Medicine, Denver, CO, United States of America.
Satish L; Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United States of America.; College of Pharmacy, University of Cincinnati College of Medicine, Cincinnati, OH, United States of America.
Kotagiri N; Research Department, Shriners Hospitals for Children- Cincinnati, Cincinnati, OH, United States of America.
Hassett DJ; Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, Cincinnati, OH, United States of America.
Źródło:
PloS one [PLoS One] 2021 Mar 03; Vol. 16 (3), pp. e0247513. Date of Electronic Publication: 2021 Mar 03 (Print Publication: 2021).
Typ publikacji:
Journal Article; Research Support, U.S. Gov't, Non-P.H.S.
Język:
English
Imprint Name(s):
Original Publication: San Francisco, CA : Public Library of Science
MeSH Terms:
Afghan Campaign 2001-*
Iraq War, 2003-2011*
Acinetobacter Infections/*microbiology
Acinetobacter baumannii/*drug effects
Anti-Bacterial Agents/*pharmacology
Disinfectants/*pharmacology
Drug Resistance, Multiple, Bacterial/*drug effects
Edetic Acid/*pharmacology
Nitrites/*pharmacology
Wound Infection/*microbiology
Acinetobacter Infections/epidemiology ; Acinetobacter baumannii/genetics ; Adult ; Afghanistan/epidemiology ; Anti-Bacterial Agents/chemistry ; Biofilms/drug effects ; Cells, Cultured ; Disinfectants/chemistry ; Drug Combinations ; Drug Resistance, Multiple, Bacterial/genetics ; Edetic Acid/chemistry ; Fibroblasts/drug effects ; Fibroblasts/metabolism ; Gene Expression/drug effects ; Humans ; Iraq/epidemiology ; Microbial Sensitivity Tests ; Nitrites/chemistry ; Polymerase Chain Reaction ; Skin/cytology ; Wound Infection/epidemiology
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Substance Nomenclature:
0 (AB569)
0 (Anti-Bacterial Agents)
0 (Disinfectants)
0 (Drug Combinations)
0 (Nitrites)
9G34HU7RV0 (Edetic Acid)
Entry Date(s):
Date Created: 20210303 Date Completed: 20210913 Latest Revision: 20211221
Update Code:
20240105
PubMed Central ID:
PMC7928478
DOI:
10.1371/journal.pone.0247513
PMID:
33657146
Czasopismo naukowe
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 (HDFa) revealed an upper toxicity limit of 3 mM EDTA plus 64 mM A-NO2-, and thus are in the therapeutic range for effective Ab and Acinetobacter spp. treatment. Following treatment of Ab strain ATCC 19606 with AB569, quantitative PCR analysis of selected genes products to be responsive to AB569 revealed up-regulation of iron regulated genes involved in siderophore production, siderophore biosynthesis non-ribosomal peptide synthetase module (SBNRPSM), and siderophore biosynthesis protein monooxygenase (SBPM) when compared to untreated organisms. Taken together, treating Ab infections with AB569 at inhibitory concentrations reveals the potential clinical application of preventing Ab from gaining an early growth advantage during infection followed by extensive bactericidal activity upon subsequent exposures.
Competing Interests: The authors have declared that no competing interests exist.
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