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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
- Source :
- PLoS ONE, Vol 16, Iss 3, p e0247513 (2021), PLoS ONE
- Publication Year :
- 2021
- Publisher :
- Public Library of Science (PLoS), 2021.
-
Abstract
- 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.
- Subjects :
- Bacterial Diseases
Acinetobacter baumannii
0301 basic medicine
Siderophore
Antibiotics
Gene Expression
Pathology and Laboratory Medicine
Polymerase Chain Reaction
chemistry.chemical_compound
Medical Conditions
Drug Resistance, Multiple, Bacterial
Medicine and Health Sciences
Cells, Cultured
Skin
Multidisciplinary
Acinetobacter
Afghan Campaign 2001
biology
Antimicrobials
Chemistry
Drugs
Neurodegenerative Diseases
Bacterial Pathogens
Anti-Bacterial Agents
Drug Combinations
Infectious Diseases
Neurology
Medical Microbiology
Iraq
Toxicity
Medicine
Pathogens
Research Article
Acinetobacter Infections
Adult
Multiple Sclerosis
medicine.drug_class
Science
Immunology
030106 microbiology
Ethylenediaminetetraacetic acid
Microbial Sensitivity Tests
Microbiology
Autoimmune Diseases
03 medical and health sciences
Antibiotic resistance
Therapeutic index
Microbial Control
Genetics
medicine
Humans
Microbial Pathogens
Iraq War, 2003-2011
Edetic Acid
Nitrites
Pharmacology
Bacteria
Organisms
Afghanistan
Biology and Life Sciences
Bacteriology
Fibroblasts
biology.organism_classification
Demyelinating Disorders
030104 developmental biology
Biofilms
Antibiotic Resistance
Wound Infection
Clinical Immunology
Antimicrobial Resistance
Clinical Medicine
Bacterial Biofilms
Disinfectants
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 16
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....7ddaccc9e28fba233b003ca8a68edb85