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Infection and Immunity, April 2008, p. 1599-1607, Vol. 76, No. 4
0019-9567/08/$08.00+0     doi:10.1128/IAI.01253-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Mining the Moraxella catarrhalis Genome: Identification of Potential Vaccine Antigens Expressed during Human Infection{triangledown}

Elizabeth A. Ruckdeschel,1 Charmaine Kirkham,2 Alan J. Lesse,1,2,3,5 Zihua Hu,4 and Timothy F. Murphy1,2,5*

Department of Microbiology,1 Department of Medicine,2 Department of Pharmacology & Toxicology,3 Center for Computational Research, New York State Center of Excellence in Bioinformatics & Life Sciences, University at Buffalo, State University of New York,4 Veterans Affairs Western New York Healthcare System, Buffalo, New York 142155

Received 12 September 2007/ Returned for modification 2 November 2007/ Accepted 22 January 2008

Moraxella catarrhalis is an important cause of respiratory infections in adults and otitis media in children. Developing an effective vaccine would reduce the morbidity, mortality, and costs associated with such infections. An unfinished genome sequence of a strain of M. catarrhalis available in the GenBank database was analyzed, and open reading frames predicted to encode potential vaccine candidates were identified. Three genes encoding proteins having molecular masses of approximately 22, 75, and 78 kDa (designated Msp [Moraxella surface proteins]) (msp22, msp75, and msp78, respectively) were determined to be conserved by competitive hybridization using a microarray, PCR, and sequencing of the genes in clinical isolates of M. catarrhalis. The genes were transcribed when M. catarrhalis was grown in vitro. These genes were amplified by PCR and cloned into Escherichia coli expression vectors. Recombinant proteins were generated and then studied using enzyme-linked immunosorbent assays with preacquisition and postclearance serum and sputum samples from 31 adults with chronic obstructive pulmonary disease (COPD) who acquired and cleared M. catarrhalis. New antibody responses to the three proteins were observed for a small proportion of the patients with COPD, indicating that these proteins were expressed during human infection. These studies indicate that the Msp22, Msp75, and Msp78 proteins, whose genes were discovered using genome mining, are highly conserved among strains, are expressed during human infection with M. catarrhalis, and represent potential vaccine antigens.

* Corresponding author. Mailing address: VA Western New York Healthcare System, Medical Research 151, 3495 Bailey Avenue, Buffalo, NY 14215. Phone: (716) 862-7874. Fax: (716) 862-6526. E-mail: murphyt{at}buffalo.edu

{triangledown} Published ahead of print on 28 January 2008.

Editor: R. P. Morrison

Infection and Immunity, April 2008, p. 1599-1607, Vol. 76, No. 4
0019-9567/08/$08.00+0     doi:10.1128/IAI.01253-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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