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Infection and Immunity, October 2008, p. 4463-4468, Vol. 76, No. 10
0019-9567/08/$08.00+0     doi:10.1128/IAI.00499-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Serial Isolates of Persistent Haemophilus influenzae in Patients with Chronic Obstructive Pulmonary Disease Express Diminishing Quantities of the HMW1 and HMW2 Adhesins{triangledown}

Deborah M. Cholon,1 David Cutter,2,{dagger} Stephen K. Richardson,3 Sanjay Sethi,4 Timothy F. Murphy,4 Dwight C. Look,3 and Joseph W. St. Geme III1*

Departments of Pediatrics and Molecular Genetics and Microbiology, Duke University Medical Center, DUMC 3352, Durham, North Carolina 27710,1 Department of Pediatrics, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, Missouri 63110,2 Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa,3 University at Buffalo, State University of New York, and Veterans Affairs Western New York Healthcare System, Buffalo, New York4

Received 22 April 2008/ Returned for modification 29 May 2008/ Accepted 29 July 2008

In patients with chronic obstructive pulmonary disease (COPD), the lower respiratory tract is commonly colonized by bacterial pathogens, including nontypeable Haemophilus influenzae. The H. influenzae HMW1 and HMW2 adhesins are homologous proteins that promote bacterial adherence to respiratory epithelium and are the predominant targets of the host immune response. These adhesins undergo graded phase variation, controlled by the numbers of 7-bp repeats upstream of the HMW1 and HMW2 structural genes (hmw1A and hmw2A, respectively). In this study, we examined the levels of HMW1 and HMW2 expressed by H. influenzae isolates collected serially from patients with COPD. We found that expression of HMW1 and HMW2 in a given strain decreased over time in a majority of patients, reflecting progressive increases in the numbers of 7-bp repeats and associated with high serum titers of HMW1/HMW2-specific antibodies. We speculate that the presence of high titers of antibodies against the HMW1 and HMW2 adhesins and other immune factors in the lower respiratory tracts of patients with COPD may result in gradual selection for bacteria with reduced levels of HMW1 and HMW2.

* Corresponding author. Mailing address: Department of Pediatrics, Duke University Medical Center, DUMC 3352, Durham, NC 27710. Phone: (919) 681-4080. Fax: (919) 681-2714. E-mail: j.stgeme{at}duke.edu

{triangledown} Published ahead of print on 4 August 2008.

Editor: J. N. Weiser

{dagger} Present address: Sigma-Aldrich, Inc., St. Louis, MO.

Infection and Immunity, October 2008, p. 4463-4468, Vol. 76, No. 10
0019-9567/08/$08.00+0     doi:10.1128/IAI.00499-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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