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Journal of Bacteriology, February 2001, p. 1259-1268, Vol. 183, No. 4
0021-9193/01/$04.00+0   DOI: 10.1128/JB.183.4.1259-1268.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Systematic Identification of Selective Essential Genes in Helicobacter pylori by Genome Prioritization and Allelic Replacement Mutagenesis

Alison F. Chalker,1,* Heather W. Minehart,1 Nicky J. Hughes,1 Kristin K. Koretke,2 Michael A. Lonetto,2 Kerry K. Brinkman,3 Patrick V. Warren,2 Andrei Lupas,2 Michael J. Stanhope,2 James R. Brown,2 and Paul S. Hoffman1

Department of Anti-Infective Research1 and Department of Bioinformatics,2 SmithKline Beecham Pharmaceuticals, Collegeville, Pennsylvania 19426, and Department of Biology, Pennsylvania State University, University Park, Pennsylvania 168023

Received 27 September 2000/Accepted 17 November 2000

A comparative genomic approach was used to identify Helicobacter pylori 26695 open reading frames (ORFs) which are conserved in H. pylori J99 but highly diverged in other eubacteria. A survey of selected pathways of central intermediary metabolism was also carried out, and genes with a potentially selective role in H. pylori were identified. Forty-five ORFs identified in these two analyses were screened using a rapid vector-free allelic replacement mutagenesis technique, and 33 were shown to be essential in vitro. Notably, 13 ORFs gave essentiality results which are unexpected in view of their known or proposed functions, and phylogenetic analysis was used to investigate the annotation of 7 such ORFs which are highly diverged. We propose that the products of a number of these H. pylori-specific essential genes may be suitable targets for novel anti-H. pylori therapies.

* Corresponding author. Mailing address: Department of Anti-Infective Research, SmithKline Beecham Pharmaceuticals, 1250 South Collegeville Rd., Collegeville, PA 19426-0989. Phone: (610) 917-6366. Fax: (610) 917-7901. E-mail: Alison_F_Chalker{at}sbphrd.com.

Journal of Bacteriology, February 2001, p. 1259-1268, Vol. 183, No. 4
0021-9193/01/$04.00+0   DOI: 10.1128/JB.183.4.1259-1268.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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