Ahn Y.-Y.,Indiana University Bloomington |
Lee D.-S.,Inha University |
Burd H.,Igenbio Inc. |
Blank W.,Igenbio Inc. |
Kapatral V.,Igenbio Inc.
PLoS ONE | Year: 2014
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. © 2014 Ahn et al.
Wilder H.K.,Baylor College of Medicine |
Raffel S.J.,National Institute of Allergy and Infectious Diseases |
Barbour A.G.,University of California at Irvine |
Porcella S.F.,National Institute of Allergy and Infectious Diseases |
And 6 more authors.
PLoS ONE | Year: 2016
Adaptation is key for survival as vector-borne pathogens transmit between the arthropod and vertebrate, and temperature change is an environmental signal inducing alterations in gene expression of tick-borne spirochetes. While plasmids are often associated with adaptation, complex genomes of relapsing fever spirochetes have hindered progress in understanding the mechanisms of vector colonization and transmission. We utilized recent advances in genome sequencing to generate the most complete version of the Borrelia turicatae 150 kb linear megaplasmid (lp150). Additionally, a transcriptional analysis of open reading frames (ORFs) in lp150 was conducted and identified regions that were up-regulated during in vitro cultivation at tick-like growth temperatures (22°C), relative to bacteria grown at 35°C and infected murine blood. Evaluation of the 3' end of lp150 identified a cluster of ORFs that code for putative surface lipoproteins. With a microbe's surface proteome serving important roles in pathogenesis, we confirmed the ORFs expression in vitro and in the tick compared to spirochetes infecting murine blood. Transcriptional evaluation of lp150 indicates the plasmid likely has essential roles in vector colonization and/or initiating mammalian infection. These results also provide a much needed transcriptional framework to delineate the molecular mechanisms utilized by relapsing fever spirochetes during their enzootic cycle.
Vongsawan A.A.,Armed Forces Research Institute of Medical science |
Kapatral V.,Igenbio Inc. |
Vaisvil B.,Igenbio Inc. |
Burd H.,Igenbio Inc. |
And 3 more authors.
FEMS Microbiology Letters | Year: 2015
We sequenced and analyzed Shigella dysenteriae strain Sd1617 serotype 1 that is widely used as model strain for vaccine design, trials and research. A combination of next-generation sequencing platforms and assembly yielded two contigs representing a chromosome size of 4.34 Mb and the large virulence plasmid of 177 kb. This genome sequence is compared with other Shigella genomes in order to understand gene complexity and pathogenic factors. © FEMS 2015.