Abstract
Outer membrane protein (OMP) CopB, an iron-repressible 81-kDa major OMP of Moraxella (Branhamella) catarrhalis has been a major focus of investigation. To assess CopB as a potential vaccine antigen, we elucidated the degree of antigenic and sequence heterogeneity in this protein among strains of M. catarrhalis. Two monoclonal antibodies, 1F5 and 2.9F, which bind to surface-exposed epitopes on CopB recognized 60 and 70% of the strains, respectively. The degree of sequence heterogeneity in CopB was assessed by cloning and sequencing the CopB gene from two different strains of M. catarrhalis and comparing with the published sequence. There was 92 to 96% homology between the sequences at the nucleotide level and 90 to 95% homology at the amino acid level. The variability in the protein sequence is confined mainly to three moderately variable regions. Restriction fragment length polymorphism (RFLP) analysis of the CopB genes obtained from 20 diverse strains by PCR was performed. Ninety percent of the potential restriction sites in the constant regions and 47% of the potential restriction sites in the variable regions were present in the 20 strains, indicating that the pattern of variable and constant areas in the CopB gene is a general pattern among strains of M. catarrhalis. We conclude that the CopB gene is largely conserved among strains of M. catarrhalis and contains discrete regions which show moderate heterogeneity among strains.
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- Aebi C., Stone B., Beucher M., Cope L. D., Maciver I., Thomas S. E., McCracken G. H., Jr, Sparling P. F., Hansen E. J. Expression of the CopB outer membrane protein by Moraxella catarrhalis is regulated by iron and affects iron acquisition from transferrin and lactoferrin. Infect Immun. 1996 Jun;64(6):2024–2030. doi: 10.1128/iai.64.6.2024-2030.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bartos L. C., Murphy T. F. Comparison of the outer membrane proteins of 50 strains of Branhamella catarrhalis. J Infect Dis. 1988 Oct;158(4):761–765. doi: 10.1093/infdis/158.4.761. [DOI] [PubMed] [Google Scholar]
- Beucher M., Sparling P. F. Cloning, sequencing, and characterization of the gene encoding FrpB, a major iron-regulated, outer membrane protein of Neisseria gonorrhoeae. J Bacteriol. 1995 Apr;177(8):2041–2049. doi: 10.1128/jb.177.8.2041-2049.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Campagnari A. A., Shanks K. L., Dyer D. W. Growth of Moraxella catarrhalis with human transferrin and lactoferrin: expression of iron-repressible proteins without siderophore production. Infect Immun. 1994 Nov;62(11):4909–4914. doi: 10.1128/iai.62.11.4909-4914.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Doyle R. J., Nedjat-Haiem F., Keller K. F., Frasch C. E. Diagnostic value of interactions between members of the family Neisseriaceae and lectins. J Clin Microbiol. 1984 Mar;19(3):383–387. doi: 10.1128/jcm.19.3.383-387.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gehanno P., Berche P., Boucot I., Lambert-Zechovsky N., Bingen E., Gres J. J., Rollin C. Comparative efficacy and safety of cefprozil and amoxycillin/clavulanate in the treatment of acute otitis media in children. J Antimicrob Chemother. 1994 Jun;33(6):1209–1218. doi: 10.1093/jac/33.6.1209. [DOI] [PubMed] [Google Scholar]
- Goldblatt D., Turner M. W., Levinsky R. J. Branhamella catarrhalis: antigenic determinants and the development of the IgG subclass response in childhood. J Infect Dis. 1990 Nov;162(5):1128–1135. doi: 10.1093/infdis/162.5.1128. [DOI] [PubMed] [Google Scholar]
- Hager H., Verghese A., Alvarez S., Berk S. L. Branhamella catarrhalis respiratory infections. Rev Infect Dis. 1987 Nov-Dec;9(6):1140–1149. doi: 10.1093/clinids/9.6.1140. [DOI] [PubMed] [Google Scholar]
- Helminen M. E., Maciver I., Latimer J. L., Cope L. D., McCracken G. H., Jr, Hansen E. J. A major outer membrane protein of Moraxella catarrhalis is a target for antibodies that enhance pulmonary clearance of the pathogen in an animal model. Infect Immun. 1993 May;61(5):2003–2010. doi: 10.1128/iai.61.5.2003-2010.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Helminen M. E., Maciver I., Latimer J. L., Klesney-Tait J., Cope L. D., Paris M., McCracken G. H., Jr, Hansen E. J. A large, antigenically conserved protein on the surface of Moraxella catarrhalis is a target for protective antibodies. J Infect Dis. 1994 Oct;170(4):867–872. doi: 10.1093/infdis/170.4.867. [DOI] [PubMed] [Google Scholar]
- Helminen M. E., Maciver I., Paris M., Latimer J. L., Lumbley S. L., Cope L. D., McCracken G. H., Jr, Hansen E. J. A mutation affecting expression of a major outer membrane protein of Moraxella catarrhalis alters serum resistance and survival in vivo. J Infect Dis. 1993 Nov;168(5):1194–1201. doi: 10.1093/infdis/168.5.1194. [DOI] [PubMed] [Google Scholar]
- Kennett R. H. Cell fusion. Methods Enzymol. 1979;58:345–359. doi: 10.1016/s0076-6879(79)58149-x. [DOI] [PubMed] [Google Scholar]
- Klingman K. L., Murphy T. F. Purification and characterization of a high-molecular-weight outer membrane protein of Moraxella (Branhamella) catarrhalis. Infect Immun. 1994 Apr;62(4):1150–1155. doi: 10.1128/iai.62.4.1150-1155.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McLeod D. T., Ahmad F., Capewell S., Croughan M. J., Calder M. A., Seaton A. Increase in bronchopulmonary infection due to branhamella catarrhalis. Br Med J (Clin Res Ed) 1986 Apr 26;292(6528):1103–1105. doi: 10.1136/bmj.292.6528.1103. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murphy T. F., Bartos L. C. Surface-exposed and antigenically conserved determinants of outer membrane proteins of Branhamella catarrhalis. Infect Immun. 1989 Oct;57(10):2938–2941. doi: 10.1128/iai.57.10.2938-2941.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murphy T. F., Loeb M. R. Isolation of the outer membrane of Branhamella catarrhalis. Microb Pathog. 1989 Mar;6(3):159–174. doi: 10.1016/0882-4010(89)90066-1. [DOI] [PubMed] [Google Scholar]
- Murphy T. F., Sethi S. Bacterial infection in chronic obstructive pulmonary disease. Am Rev Respir Dis. 1992 Oct;146(4):1067–1083. doi: 10.1164/ajrccm/146.4.1067. [DOI] [PubMed] [Google Scholar]
- Nicotra B., Rivera M., Luman J. I., Wallace R. J., Jr Branhamella catarrhalis as a lower respiratory tract pathogen in patients with chronic lung disease. Arch Intern Med. 1986 May;146(5):890–893. [PubMed] [Google Scholar]
- Pettersson A., Maas A., van Wassenaar D., van der Ley P., Tommassen J. Molecular characterization of FrpB, the 70-kilodalton iron-regulated outer membrane protein of Neisseria meningitidis. Infect Immun. 1995 Oct;63(10):4181–4184. doi: 10.1128/iai.63.10.4181-4184.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sethi S., Hill S. L., Murphy T. F. Serum antibodies to outer membrane proteins (OMPs) of Moraxella (Branhamella) catarrhalis in patients with bronchiectasis: identification of OMP B1 as an important antigen. Infect Immun. 1995 Apr;63(4):1516–1520. doi: 10.1128/iai.63.4.1516-1520.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van der Ley P., van der Biezen J., Sutmuller R., Hoogerhout P., Poolman J. T. Sequence variability of FrpB, a major iron-regulated outer-membrane protein in the pathogenic neisseriae. Microbiology. 1996 Nov;142(Pt 11):3269–3274. doi: 10.1099/13500872-142-11-3269. [DOI] [PubMed] [Google Scholar]