Metabolic network analysis-based identification of antimicrobial drug targets in category A bioterrorism agents.
The 2001 anthrax mail attacks in the United States demonstrated the potential threat of bioterrorism, hence driving the need to develop sophisticated treatment and diagnostic protocols to counter biological warfare. Here, by performing flux balance analyses on the fully-annotated metabolic networks of multiple, whole genome-sequenced bacterial strains, we have identified a large number of metabolic enzymes as potential drug targets for each of the three Category A-designated bioterrorism agents including Bacillus anthracis, Francisella tularensis and Yersinia pestis. Nine metabolic enzymes- belonging to the coenzyme A, folate, phosphatidyl-ethanolamine and nucleic acid pathways common to all strains across the three distinct genera were identified as targets. Antimicrobial agents against some of these enzymes are available. Thus, a combination of cross species-specific antibiotics and common antimicrobials against shared targets may represent a useful combinatorial therapeutic approach against all Category A bioterrorism agents.
School of Informatics and Computing, Indiana University, Bloomington, Indiana, United States of America.
Yong-Yeol
YY
Ahn
Department of Natural Medical Sciences and Department of Physics, Inha University, Incheon, Korea.
Deok-Sun
DS
Lee
Igenbio.Inc, Chicago, Illinois, United States of America.
Henry
H
Burd
Igenbio.Inc, Chicago, Illinois, United States of America.
William
W
Blank
Igenbio.Inc, Chicago, Illinois, United States of America.
Vinayak
V
Kapatral
D000890:Anti-Infective Agents / Q000494:pharmacology*; D001408:Bacillus anthracis / Q000187:drug effects* / Q000472:pathogenicity; D023482:Bioterrorism; D005604:Francisella tularensis / Q000187:drug effects* / Q000472:pathogenicity; D015010:Yersinia pestis / Q000187:drug effects* / Q000472:pathogenicity
D000890:Anti-Infective Agents