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Open AcceMeeting abstract
Bioinformatics determination of ETEC signature genes as potential
targets for molecular diagnosis and reverse vaccinology
Heba M Amin1, Abdel-Gawad M Hashem2 and Ramy K Aziz*2
Address: 1Department of Microbiology and Immunology, Faculty of Pharmacy, MSA University, Cairo, Egypt and 2Department of Microbiology
and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt
Email: Ramy K Aziz* - ramy.aziz@salmonella.org
* Corresponding author
Background
Genomes of the model bacterium, Escherichia coli, exhibit
high plasticity caused by gene gain/loss via pathoadaptive
mutations, genetic rearrangement, and horizontal gene
transfer [1,2]. This genetic variability is also translated
into a remarkable phenotypic and pathotypic diversity:
while some E. coli strains normally inhabit the mamma-
lian colon, other pathotypes cause a wide range of intesti-
nal and extraintestinal diseases that include mild
intestinal disturbance but also severe urinary tract infec-
tions and outbreaks of shigellosis-like dysentery or chol-
era-like watery diarrhea [1]. In this study, we focus on
enterotoxigenic E. coli (ETEC), one of the world's deadliest
infectious agents, which also represents a serious public
health in Egypt's rural areas. Our aim is to integrate mul-
tiple bioinformatics tools to determine horizontally trans-
ferred, pathotype-specific signature genes as targets for
specific, high-throughput molecular diagnostic tools and
reverse vaccinology screens.
Methods and results
To estimate the extent of horizontal gene transfer in ETEC,
we used a combination of bioinformatics tools, including
GC%, comparative genometrics analysis [3], and web-
based prediction of pathogenicity islands via IslandPath
http://www.pathogenomics.sfu.ca/islandpath[4]. Because
E. coli strains are typically polylysogenic [5], we used the
ACLAME Prophinder tool http://aclame.ulb.ac.be/Tools/
mine ETEC pathotype-specific genes or signature genes,
we used comparative genomic tools available in the
National Microbial Pathogen Data Resource (NMPDR)
platform http://www.nmpdr.org, including the Signature
Genes Tool and the Homolog Spreadsheet Tool [7]. We
identified 128 genes that differentiate this pathotype from
other E. coli strains, based on bidirectional-best-hit signa-
ture analysis. We also identified 94 genes that are charac-
teristic to two closely related strains (24377A and 2348/
69). Many of the ETEC-specific genes were mapped to
prophages, prophage-like elements, and other patho-
genicity islands; however, some of these signature genes,
e.g., ORFs 21–39 in strain 24377A, seem to be rather lost
in other E. coli strains (as they are conserved among other
enterobacteria, e.g., Shigella and Salmonella). Our ongoing
studies are testing some of these ETEC-specific genes as
targets for multiplex PCR amplification to develop a rapid
diagnostic typing method. Future studies will analyze the
surface-association and antigenicity of these signature
gene products as a first step in a reverse vaccinology strat-
egy to develop novel ETEC vaccines.
References
1. Dobrindt U: (Patho-)Genomics of Escherichia coli. Int J Med
Microbiol 2005, 295(6–7):357-371.
2. Morschhauser J, Kohler G, Ziebuhr W, Blum-Oehler G, Dobrindt U,
Hacker J: Evolution of microbial pathogens. Philos Trans R Soc
Lond B Biol Sci 2000, 355(1397):695-704.
3. Roten CA, Gamba P, Barblan JL, Karamata D: Comparative Geno-
from UT-ORNL-KBRIN Bioinformatics Summit 2009
Pikeville, TN, USA. 20–22 March 2009
Published: 25 June 2009
BMC Bioinformatics 2009, 10(Suppl 7):A8 doi:10.1186/1471-2105-10-S7-A8
<supplement> <title> <p>UT-ORNL-KBRIN Bioinformatics Summit 2009</p> </title> <editor>Eric C Rouchka and Julia Krushkal</editor> <note>Meeting abstracts – A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/pdf/1471-2105-10-S7-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1471-2105-10-S7-info.pdf</url> </supplement>
This abstract is available from: http://www.biomedcentral.com/1471-2105/10/S7/A8
© 2009 Amin et al; licensee BioMed Central Ltd. Page 1 of 2
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Prophinder[6] to predict complete or rudimentary
prophages scattered within the ETEC genome. To deter-
metrics (CG): a database dedicated to biometric compari-
sons of whole genomes. Nucleic Acids Res 2002, 30(1):142-144.

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