Abstract
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.
Highlights
Bacterial Category A agents include Bacillus anthracis, Yersinia pestis, Francisella tularensis, and the botulism toxin of Clostridium botulinum [1]
Among the enzymes involved in cell wall biosynthesis, phospho-N-acetylmuramoyl-pentapeptide-transferase (MraY) involved in peptidoglycan biosynthesis is essential, as Bacterial genome variations are manifested in the metabolic or physiological characteristics of a given organism
Anthracis, F. tularensis and Y. pestis strains for common target identification
Summary
Bacterial Category A agents include Bacillus anthracis (anthrax), Yersinia pestis (bubonic plague), Francisella tularensis (tularemia), and the botulism toxin of Clostridium botulinum [1]. A systematic method for the analysis of multiple strains and a blueprint for antimicrobial discovery using genomics and computational tools for microbes have been recently described [3]. These computational approaches are highly cost effective and can be used to identify sets of targets across these biological warfare agents. The Gram-positive agent causative of anthrax is naturally found in animals and in soil worldwide. They can survive both under aerobic and anaerobic conditions and can form heat resistant spores that make it an ideal agent for biological warfare
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