PMID- 33657146
OWN - NLM
STAT- MEDLINE
DCOM- 20210913
LR  - 20211221
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 16
IP  - 3
DP  - 2021
TI  - 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.
PG  - e0247513
LID - 10.1371/journal.pone.0247513 [doi]
LID - e0247513
AB  - 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.
FAU - Bogue, Amy L
AU  - Bogue AL
AD  - Department of Molecular Genetics, Biochemistry and Microbiology, University of 
      Cincinnati College of Medicine, Cincinnati, OH, United States of America.
AD  - Wright-Patterson Air Force Base, Dayton (Wright-Patterson Air Force Base), 
      Dayton, OH, United States of America.
FAU - Panmanee, Warunya
AU  - Panmanee W
AD  - Department of Molecular Genetics, Biochemistry and Microbiology, University of 
      Cincinnati College of Medicine, Cincinnati, OH, United States of America.
FAU - McDaniel, Cameron T
AU  - McDaniel CT
AD  - Department of Molecular Genetics, Biochemistry and Microbiology, University of 
      Cincinnati College of Medicine, Cincinnati, OH, United States of America.
FAU - Mortensen, Joel E
AU  - Mortensen JE
AD  - Diagnostic Infectious Disease Testing Laboratory and Department of Pediatrics, 
      Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States of 
      America.
FAU - Kamau, Edwin
AU  - Kamau E
AD  - Walter Reed National Military Medical Center (WRNMMC), Bethesda, MD, United 
      States of America.
FAU - Actis, Luis A
AU  - Actis LA
AD  - Department of Microbiology, Miami University, Oxford, OH, United States of 
      America.
FAU - Johannigman, Jay A
AU  - Johannigman JA
AD  - U.S. Army Institute of Surgical Research, San Antonio, TX, United States of 
      America.
FAU - Schurr, Michael J
AU  - Schurr MJ
AD  - Department of Immunology and Microbiology, University of Colorado Anschutz School 
      of Medicine, Denver, CO, United States of America.
FAU - Satish, Latha
AU  - Satish L
AD  - Department of Pathology and Laboratory Medicine, University of Cincinnati College 
      of Medicine, Cincinnati, OH, United States of America.
AD  - College of Pharmacy, University of Cincinnati College of Medicine, Cincinnati, 
      OH, United States of America.
FAU - Kotagiri, Nalinikanth
AU  - Kotagiri N
AUID- ORCID: 0000-0003-0066-4563
AD  - Research Department, Shriners Hospitals for Children- Cincinnati, Cincinnati, OH, 
      United States of America.
FAU - Hassett, Daniel J
AU  - Hassett DJ
AUID- ORCID: 0000-0003-2300-4955
AD  - Department of Molecular Genetics, Biochemistry and Microbiology, University of 
      Cincinnati College of Medicine, Cincinnati, OH, United States of America.
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20210303
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (AB569)
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Disinfectants)
RN  - 0 (Drug Combinations)
RN  - 0 (Nitrites)
RN  - 9G34HU7RV0 (Edetic Acid)
SB  - IM
MH  - Acinetobacter Infections/epidemiology/*microbiology
MH  - Acinetobacter baumannii/*drug effects/genetics
MH  - Adult
MH  - *Afghan Campaign 2001-
MH  - Afghanistan/epidemiology
MH  - Anti-Bacterial Agents/chemistry/*pharmacology
MH  - Biofilms/drug effects
MH  - Cells, Cultured
MH  - Disinfectants/chemistry/*pharmacology
MH  - Drug Combinations
MH  - Drug Resistance, Multiple, Bacterial/*drug effects/genetics
MH  - Edetic Acid/chemistry/*pharmacology
MH  - Fibroblasts/drug effects/metabolism
MH  - Gene Expression/drug effects
MH  - Humans
MH  - Iraq/epidemiology
MH  - *Iraq War, 2003-2011
MH  - Microbial Sensitivity Tests
MH  - Nitrites/chemistry/*pharmacology
MH  - Polymerase Chain Reaction
MH  - Skin/cytology
MH  - Wound Infection/epidemiology/*microbiology
PMC - PMC7928478
COIS- The authors have declared that no competing interests exist.
EDAT- 2021/03/04 06:00
MHDA- 2021/09/14 06:00
PMCR- 2021/03/03
CRDT- 2021/03/03 17:10
PHST- 2020/09/14 00:00 [received]
PHST- 2021/02/08 00:00 [accepted]
PHST- 2021/03/03 17:10 [entrez]
PHST- 2021/03/04 06:00 [pubmed]
PHST- 2021/09/14 06:00 [medline]
PHST- 2021/03/03 00:00 [pmc-release]
AID - PONE-D-20-27085 [pii]
AID - 10.1371/journal.pone.0247513 [doi]
PST - epublish
SO  - PLoS One. 2021 Mar 3;16(3):e0247513. doi: 10.1371/journal.pone.0247513. 
      eCollection 2021.