Characterization of the Moraxella catarrhalis Opa-Like Protein, OlpA, Reveals a Phylogenetically Conserved Family of Outer Membrane Proteins

Abstract

Moraxella catarrhalis is a human-restricted pathogen that can cause respiratory tract infections. In this study, we identified a previously uncharacterized 24-kDa outer membrane protein with a high degree of similarity to Neisseria Opa protein adhesins, with a predicted ␤-barrel structure consisting of eight antiparallel ␤-sheets with four surface-exposed loops. In striking contrast to the antigenically variable Opa proteins, the M. catarrhalis Opa-like protein (OlpA) is highly conserved and constitutively expressed, with 25 of 27 strains corresponding to a single variant. Protease treatment of intact bacteria and isolation of outer membrane vesicles confirm that the protein is surface exposed yet does not bind host cellular receptors recognized by neisserial Opa proteins. Genome-based analyses indicate that OlpA and Opa derive from a conserved family of proteins shared by a broad array of gram-negative bacteria.Moraxella catarrhalis is an obligate parasite of humans that can cause disease in both the upper and lower respiratory tracts. In the upper respiratory tract, M. catarrhalis is responsible for cases of sinusitis and is the third leading cause of otitis media in infants, after only Haemophilus influenzae and Streptococcus pneumoniae (5,10,18,24). In the lower respiratory tract, M. catarrhalis can cause respiratory infections in adults with chronic obstructive pulmonary disease, resulting in increased morbidity and mortality of these patients (27,28). M. catarrhalis is thought to be responsible for 2 to 4 million infectious exacerbations of chronic obstructive pulmonary disease in the United States each year (25), and there is significant cost in treating disease related to M. catarrhalis, which is complicated in part by a rise in antibiotic-resistant strains (2, 30). This makes development of a vaccine an exciting and important goal.The mechanisms involved in pathogenesis and virulence of M. catarrhalis remain poorly defined. Attachment to host mucosal surfaces is an important step in colonization. Recently, M. catarrhalis genes encoding the type IV pilus were identified and characterized (23), leading to speculation that this structure mediates initial attachment to mucosal epithelia in a manner similar to that of the closely related pathogenic Neisseria spp. (9). M. catarrhalis can also interact with the A549 human lung epithelial carcinoma cell line through the bacterium's outer membrane protein CD (16) and Hag (17) adhesins. Another adhesin, UspA1, promotes attachment to Chang human conjunctiva-derived epithelial cells (21) and was recently shown to mediate adherence via the host cellular receptor CEACAM1 (15). Human CEACAM1 is also engaged by the adhesins of other bacteria, including the Haemophilus influenzae P5 protein (14) and the Opa proteins of pathogenic and commensal Neisseria spp. (12,29,35). Remarkably, the UspA1, P5, and Opa proteins are not related, indicating a clear example of convergent evolution by these various human-restricted bacteria.Considering the importance of the Opa family of ...

The modA10 phasevarion of nontypeable Haemophilus influenzae R2866 regulates multiple virulence-associated traits

“…Previous studies have shown that NTHi can survive within the lysosomal compartment in eukaryotic cells [51], that these NTHi cells were viable, and that intercellular residence shields the bacteria from the host immune system and antibiotics, sustaining mucosal colonization when the bacteria emerge apically [52]. Transcytosis into the submucosa is a mechanism that can shield the bacterium from mucosal host defense, and lead to bacterial replication in blood.. NTHi strain 12 has been shown to bind to α (2-3) sialic acid on the surface of M cells in the guinea pig conjunctiva and then invaded [47].…”

“…The putative amino acid sequence of OlpA2 has no significant homology to the sequence of OapA in Rd KW20 [51]. OlpA2 has homology to a Moraxella catarrhalis outer membrane protein (encoded by olpA ) which is involved in adherence [52] and resistance to normal human serum [53]. …”

Complement evasion by the human respiratory tract pathogens Haemophilus influenzae and Moraxella catarrhalis

“…Moraxella catarrhalis outer membrane protein OlpA (Opa-like protein A; 24 kDa) [89] is related to the neisserial Opa adhesins that bind both carcinoembryonic antigen-related cell adhesion molecule (CAECAM) and heparan sulfate proteoglycan receptors. OlpA binds factor H to the bacterial surface of Moraxella and mediates resistance to the alternative pathway of complement activation [90].…”

Vaccine targets againstMoraxella catarrhalis

“…More recently, sustained efforts have achieved progresses in identifying more new M. catarrhalis vaccine antigens such as OlpA [97], ORF113 [98] and liposome-associated OMPs [99]. These antigens have shown the features of a vaccine antigen such as immunogenic, exposed or partially exposed to the surface, and conserved.…”

“…These antigens have shown the features of a vaccine antigen such as immunogenic, exposed or partially exposed to the surface, and conserved. Some of the antigens play key roles in the pathogenesis of M. catarrhalis infections such as NP colonization and complement resistance [97-99]. Further investigation of these target molecules may prove they are potential M. catarrhalis vaccine candidates.…”