Moraxella catarrhalis is a gram-negative bacterium that is mainly responsible for respiratory tract infections. In this study we report a novel outer membrane protein (OMP), designated M35, with a molecular mass of 36.1 kDa. This protein was structurally homologous to classic gram-negative porins, such as OMP C from Escherichia coli and OMP K36 from Klebsiella pneumoniae, with a predicted structure of 8 surface loops and 16 antiparallel -sheets. The DNA sequences of the genes from 18 diverse clinical isolates showed that the gene was highly conserved (99.6 to 100% of nucleotides), with only one isolate (ID78LN266) having base variations that resulted in amino acid substitutions. Electrophoresis and analysis of recognition of the protein using mouse anti-M35 sera showed that M35 was expressed on the bacterial surface and constitutively expressed across M. catarrhalis isolates, with only ID78LN266 showing poor antibody recognition. Our results showed that the single amino acid mutation in loop 3 significantly affected antibody recognition, indicating that loop 3 appeared to contain an immunodominant B-cell epitope. The antibody specificity to loop 3 may be a potential mechanism for evasion of host immune responses targeted to M35, since loop 3 should theoretically orientate into the porin channel. Thus, M35 is a highly conserved, surface-expressed protein that is of significance for its potential functional role as an M. catarrhalis porin and is of interest as a vaccine candidate.Moraxella catarrhalis, a gram-negative bacterium, is predominantly responsible for respiratory tract infections, such as otitis media, sinusitis, and exacerbations of chronic obstructive pulmonary disease (17,24,30). On rare occasions, it can also cause more serious diseases, such as meningitis and septicemia, although these occur mainly in immunocompromised populations and neonates (7, 23). M. catarrhalis pathogenesis and virulence factors are not well understood. For a long time, limited research was undertaken on this bacterium, since it was considered a normal commensal. The acceptance of M. catarrhalis as a pathogen, and its remarkably rapid development of resistance to -lactam antibiotics (12,14), have stimulated research into the pathogenesis of infection and characterization of the bacterium.The majority of research into M. catarrhalis has been focused on the identification and characterization of outer membrane proteins (OMP), with a view to assessing their suitability as vaccine antigens. An ideal vaccine candidate should be highly conserved so that it can elicit an immune response that protects against all strains of the bacterium. A number of potential vaccine candidates have been identified so far, and one particular characteristic of these is conservation across strains. Two proteins that demonstrate potential as vaccine antigens, OMP E and OMP CD, appear to be well conserved (24-26) and demonstrate some similarity with porins from Escherichia coli and Pseudomonas species, respectively (24). This study reports the characte...