The Transferrin Binding Protein B of Moraxella catarrhalis Elicits Bactericidal Antibodies and Is a Potential Vaccine Antigen

Abstract

The transferrin binding protein genes (tbpA and tbpB) from two strains of Moraxella catarrhalis have been cloned and sequenced. The genomic organization of the M. catarrhalis transferrin binding protein genes is unique among known bacteria in that tbpA precedes tbpB and there is a third gene located between them. The deduced sequences of the M. catarrhalis TbpA proteins from two strains were 98% identical, while those of the TbpB proteins from the same strains were 63% identical and 70% similar. The third gene, tentatively called orf3, encodes a protein of approximately 58 kDa that is 98% identical between the two strains. The tbpB genes from four additional strains of M. catarrhalis were cloned and sequenced, and two potential families of TbpB proteins were identified based on sequence similarities. Recombinant TbpA (rTbpA), rTbpB, and rORF3 proteins were expressed in Escherichia coli and purified. rTbpB was shown to retain its ability to bind human transferrin after transfer to a membrane, but neither rTbpA nor rORF3 did. Monospecific anti-rTbpA and anti-rTbpB antibodies were generated and used for immunoblot analysis, which demonstrated that epitopes of M. catarrhalis TbpA and TbpB were antigenically conserved and that there was constitutive expression of the tbp genes. In the absence of an appropriate animal model, anti-rTbpA and anti-rTbpB antibodies were tested for their bactericidal activities. The anti-rTbpA antiserum was not bactericidal, but anti-rTbpB antisera were found to kill heterologous strains within the same family. Thus, if bactericidal ability is clinically relevant, a vaccine comprising multiple rTbpB antigens may protect against M. catarrhalis disease. on July 5, 2020 by guest http://iai.asm.org/ Downloaded from FIG. 2. Nucleotide sequences of the promoter regions of M. catarrhalis 4223 tbpA, orf3, and tbpB genes. (A) Putative promoter elements for tbpA, orf3, and tbpB. RBS, ribosome-binding site. (B) Comparison of Fur-binding sites from E. coli (13), N. meningitidis tbpB (20), H. influenzae tbpB (11), and M. catarrhalis 4223 tbpB. Dots indicate residues identical to the E. coli consensus sequence, and underlining indicates dyad symmetry.

The characterization of Moraxella catarrhalis carried in the general population

“…Both tbpA and tbpB were present in all isolates, which is comparable to other studies [28, 78]. Again, in agreement with prior research, lbpA and lbpB were present in 100 % of isolates [28, 79].…”

The Role of the Moraxella catarrhalis CopB Protein in Facilitating Iron Acquisition From Human Transferrin and Lactoferrin

“…This enables M. catarrhalis to directly access these proteins as a source of iron for growth and proliferate independently from other members of the microbial community that inhabit the upper respiratory tract. The critical role that these receptors play in the survival of M. catarrhalis led to preliminary studies evaluating their potential as vaccine antigens (Bonnah et al, 1998;Myers et al, 1998;Yu et al, 1999).…”