The surface protein UspA1 has been shown to play a primary role in M. catarrhalis
attachment to a variety of different cell types (1
). This association appears to result from its ability to bind host-derived molecules including fibronectin (42
), laminin (41
), and members of the CEACAM family of intercellular adhesion molecules (13
). While not considered in this study, UspA1 also interacts with components of both the classical and alternative complement pathways by interacting with both C3 (32
) and C4b (31
The diversity of functions attributed to UspA1 is remarkable. However, the various binding activities have been largely considered to be independent of each other and often with different strains of M. catarrhalis.
While it was generally assumed that each function would be conserved among UspA1 variants, the current study was prompted by our finding that prototypical M. catarrhalis
strain O35E does not bind to certain CEACAM-expressing cell lines. Since the sequence of variant UspA1 proteins is frequently unavailable, we cloned and sequenced several additional uspA1
genes to obtain a total of 10 genes encoding different UspA1 proteins. Three of the 10 UspA1 variants tested did not bind to CEACAMs (Fig. ), and each of these variants lacked a portion of the sequence that has been shown to confer CEACAM1 binding (12
). While M. catarrhalis
expresses a number of different adhesins (4
), our UspA1-deficient mutants clearly demonstrated that UspA1 was the only adhesin with the potential to confer CEACAM binding.
The lack of fibronectin binding exhibited by the UspA1 protein from M. catarrhalis
ATCC 43617 (Fig. ) is also a clear demonstration of the variant nature of individual UspA1 proteins. Fibronectin binding has been shown to mediate the adherence of M. catarrhalis
to Chang cells and, unlike CEACAM binding, has been associated with both UspA1 and UspA2 (42
). The amino acid sequence considered to contribute to fibronectin binding is present in UspA1, UspA2, and the naturally occurring chimera UspA2H; however, its association with each UspA protein is strain specific. The fact that both UspA1 and UspA2 can confer fibronectin-mediated binding to Chang cells makes it difficult to test the relative contribution of each one in the context of M. catarrhalis
. However, our nucleotide sequence analyses indicated that UspA1 from strain ATCC 43617 contained a deletion within the region that was previously shown to contribute to fibronectin binding (42
), and our binding assays demonstrated that this variant could not adhere to Chang epithelial cells.
The existence of three different M. catarrhalis isolates (O35E, TTA37, and ATCC 43617) that are unable to bind CEACAM receptors makes it intriguing to speculate how this phenotype may contribute to M. catarrhalis colonization of the nasopharynx or the production of disease in the respiratory tract. M. catarrhalis can be found as a member of the commensal flora in healthy individuals or associated with distinct diseases in either children (i.e., otitis media) or adults (i.e., exacerbations of COPD). The specific location (nasopharynx, trachea, or middle ear) and manner (swab, tympanocentesis, or aspirate) in which M. catarrhalis isolates are obtained must be considered when strain-specific differences in phenotype are analyzed. It is interesting in this regard that two of the three strains that lack the CEACAM-binding ability were isolated from adult tracheal aspirates.
While much remains to be learned about how each UspA1-associated function contributes to colonization or disease production (or both), it is clear that the ability to bind CEACAM and fibronectin is not a universally conserved function among M. catarrhalis
strains. Sequence analyses and functional assays must be performed before the spectrum of potential functions can be deduced. We must also consider that other functions, including complement binding, may also vary among M. catarrhalis
). It is therefore enticing to consider that the ability of UspA1 to engage different combinations of host receptors and serum components will elicit different cellular responses (29
) and that the different combination of activities may define the colonization ability and virulence potential of each strain.