AhagMutant ofMoraxella catarrhalisStrain O35E Is Deficient in Hemagglutination, Autoagglutination, and Immunoglobulin D-Binding Activities

Abstract

Moraxella (Branhamella) catarrhalis is an important cause of disease in both the upper and lower respiratory tracts (35,48). This unencapsulated gram-negative coccobacillus has been shown to express a number of different outer membrane proteins on its cell surface, some of which are antigenically conserved (47, 49). At present, information about the M. catarrhalis gene products that are involved in the ability of this organism to colonize the mucosa of the nasopharynx and survive in this hostile environment is limited at best. Much effort has been expended recently on documenting the human immune response to selected M. catarrhalis surface-exposed proteins (6,12,25,53,65), providing evidence that these particular gene products are expressed in vivo during otitis media or infections of the bronchial tree. A few of these outer membrane proteins now have a function ascribed to them, mainly with respect to iron acquisition (7,9,10,15,42,43).In contrast, there is relatively little known about other surface proteins of M. catarrhalis that might be involved in the ability of this organism to colonize and survive in the nasopharynx (35). The CD outer membrane protein (33) has been shown to bind middle ear mucin in vitro (51), a function that could be involved in the colonization process or in the development of otitis media. The UspA1 protein has been shown to be an adhesin, at least in vitro (38), whereas both the UspA2 protein (38) and outer membrane protein E (50) have been implicated in serum resistance. Both UspA1 and UspA2, consistent with their functional activities, have been localized to the surface of M. catarrhalis, where they are accessible to antibodies (2, 45).Scott and colleagues (16, 17) correlated both hemagglutination activity and the expression of a 200-kDa protein by some M. catarrhalis isolates with the presence of a fibrillar surface array. In addition, Sasaki and colleagues reported that the 200-kDa protein expressed by M. catarrhalis was subject to phase variation in vitro (K. Sasaki, L. Myers, S. M. Loosmore, and M. H. Klein, Abstr. 99th Gen. Meet. Am. Soc. Microbiol., abstr. B/D-306, 1999) and determined the nucleotide sequence of the gene encoding this protein (54). In the present study, we used analysis of mutants to show that this protein, designated Hag (hemagglutinin), is involved not only in hemagglutination but also in autoagglutination and the binding of human immunoglobulin D (IgD) by M. catarrhalis strain O35E. In addition, we determined that the Hag protein, together with the UspA1 and UspA2 proteins (3), all form fibrillar projections on the M. catarrhalis cell surface.

Age-related genotypic and phenotypic differences in Moraxella catarrhalis isolates from children and adults presenting with respiratory disease in 2001–2002

“…lower versus upper respiratory Age-related differences in Moraxella catarrhalis tract), which was also indicated by our own results (Janicka et al, 2002). The loss of autoagglutination ability has previously been linked to the insertional inactivation of the haemagglutinin (hag) gene, but not the uspA1 or uspA2 genes, in M. catarrhalis isolate O35E (Aebi et al, 1998;Pearson et al, 2002). From our own population-based study, it appears that the hag gene may not be equally important in influencing autoagglutination ability in all isolates of M. catarrhalis.…”

“…M. catarrhalis autoagglutination was measured according to Pearson et al (2002). Briefly, isolates were grown overnight on brain heart infusion (BHI) agar, washed and resuspended in 4 ml PBS to an OD 405 of 1.0±0.1 (Pharmacia Biotech Novaspec II).…”

The Emerging Pathogen Moraxella catarrhalis Interacts with Complement Inhibitor C4b Binding Protein through Ubiquitous Surface Proteins A1 and A2

“…3 and 4). The MID, also designated Hag (for hemagglutinin), has recently been demonstrated to function as an adhesin (5)(6)(7)(8)(9)(10)(11). Moreover, mice immunized with MID 764 -913 cleared M. catarrhalis much more efficiently as compared with mice immunized with BSA (12).…”

“…Abs against the common epitope have been found to be protective against M. catarrhalis infections in a mouse pulmonary clearance model (21). Both UspA1 and UspA2H are responsible for adhesion of M. catarrhalis to epithelial cells in vitro (10,20).…”

Immune Evasion ofMoraxella catarrhalisInvolves Ubiquitous Surface Protein A-Dependent C3d Binding

“…In recent years, focus has been on both its outer membrane protein composition and interactions with the human host (8,9). Several virulence determinants of M. catarrhalis have been identified, including M. catarrhalis IgDbinding protein/hemagglutinin, protein CD, M. catarrhalis adherence protein, and the ubiquitous surface proteins (Usp) (10)(11)(12)(13)(14)(15).…”