Early studies of the outer membrane proteins of M. catarrhalis
identified and characterized eight major proteins within this species, ranging from 98 kDa to 21 kDa and named OMP A to OMP H (29
). Several of these OMPs have now been characterized and include proteins involved in iron acquisition, e.g., CopB (7
), LbpB/A (6
), and TbpB (36
), fatty acid uptake (5
), and adhesion (22
). A role for some of these proteins in M. catarrhalis
virulence and pathogenicity has been suggested, including the UspA2 (1
) and OMP E (30
) proteins, which appear to facilitate serum resistance. Other experiments have shown that a CopB-binding monoclonal antibody (MAb10F3) could enhance the clearance of M. catarrhalis
in a mouse pulmonary disease model, binding to 70% of M. catarrhalis
isolates tested (19
). Furthermore, the finding that adults develop new serum immunoglobulin G and mucosal immunoglobulin A to bacterial surface epitopes after exacerbations of chronic obstructive pulmonary disease shows the importance of the humoral immune response to M. catarrhalis
-mediated infection (2
In this study, one-dimensional SDS-PAGE analysis of outer membrane protein extracts from several isolates of M. catarrhalis
revealed the presence of a small and novel major outer membrane protein (OMP J) which was found to exist in two major forms, with molecular masses of approximately 19 kDa and 16 kDa (OMP J1 and OMP J2, respectively). Sequence analysis and database searching indicated limited homology between the OMP J protein and ompJ
gene and other known protein and gene sequences, with the possible exception being a hypothetical protein found in a closely related Psychrobacter
sp. However, secondary structure prediction for OMP J indicated that the protein might possess a barrel-like tertiary structure, which taken in context with the presence of a signal sequence, suggests that OMP J may be an integral membrane protein. Indeed, the sequence/structure results suggest that OMP J belongs to a superfamily of proteins that include the OPA (opacity) family of proteins of Neisseria
spp., which mediate bacterial adherence to epithelial cells by interacting with (for example) the receptors for the human carcinoembryonic antigen cell adhesion molecule on human polymorphonuclear phagocytes. Other members of this superfamily include Neisseria
surface protein A (NspA), a highly conserved protein of unknown function which is a promising vaccine candidate against both Neisseria meningitidis
and Neisseria gonorrhoeae
). Structurally, the major difference between the two forms of OMP J seems to reside in the deletion of 12 amino acids forming part of a putative loop 2 region, but the consequences of this deletion with respect to the function and antigenic properties of the two proteins have yet to be determined.
PCR screening of isolates suggested that only a single copy of the ompJ gene is present in M. catarrhalis species and that it may be found in 100% of isolates, indicating a significant role for OMP J in the M. catarrhalis life cycle. No clear indication of the likely function of OMP J was obtained by inspecting neighboring ORFs, which appeared to comprise a mix of putative housekeeping genes involved in various metabolic and DNA repair activities. Note, however, that the direction of transcription of the ompJ gene lies in the opposite orientation to that of the neighboring ORFs.
A statistically significant association between the two major forms of OMP J, the genetic lineage, and the complement resistance phenotype was observed in diverse geographical isolates. However, serum resistance experiments using two ΔompJ2
mutants did not indicate a significant role for OMP J2 in facilitating complement resistance. It seems likely that the association of OMP J1 and OMP J2 with the complement phenotype is simply a consequence of their association with different genetic lineages previously associated with the differential expression of virulence traits (8
). In fact, most evidence implicates the UspA2 outer membrane protein as the major contributor to the complement resistance phenotype within this species (1
Previous investigations have shown that alterations in the expression of outer membrane proteins and lipooligosaccharide in M. catarrhalis
may significantly impact the in vivo clearance of isogenic mutants in a mouse model of pulmonary infection (25
). Studies investigating the role of ompJ2
in the clearance of M. catarrhalis
from the lungs of mice showed that the absence of OMP J2 resulted in a reduction in bacterial clearance from the lungs, suggesting that OMP J2 may actually be a target for the immune system.
In this publication, we identified and characterized a novel outer membrane protein (OMP J) of M. catarrhalis which appears to be present in two major lineage-specific forms. Furthermore, the ompJ gene appears to be universally present within the species and may play a role in immune system-mediated bacterial clearance from the lungs.