A novel group of Moraxella catarrhalis UspA proteins mediates cellular adhesion via CEACAMs and vitronectin.
Moraxella catarrhalis (Mx) is a common cause of otitis media and exacerbation of chronic obstructive pulmonary disease, an increasing worldwide problem. Surface proteins UspA1 and UspA2 of Mx bind to a number of human receptors and may function in pathogenesis. Genetic recombination events in the pathogen can generate hybrid proteins termed UspA2H. However, whether certain key functions (e.g. UspA1-specific CEACAM binding) can be exchanged between these adhesin families remains unknown. In this study, we have shown that Mx can incorporate the UspA1 CEACAM1-binding region not only into rare UspA1 proteins devoid of CEACAM-binding ability, but also into UspA2 which normally lack this capacity. Further, a screen of Mx isolates revealed the presence of novel UspA2 Variant proteins (UspA2V) in ∼14% of the CEACAM-binding population. We demonstrate that the expression of UspA2/2V with the CEACAM-binding domain enable Mx to bind both to cell surface CEACAMs and to integrins, the latter via vitronectin. Such properties of UspA2/2V have not been reported to date. The studies demonstrate that the UspA family is much more heterogeneous than previously believed and illustrate the in vivo potential for exchange of functional regions between UspA proteins which could convey novel adhesive functions whilst enhancing immune evasion.
School of Cellular & Molecular Medicine, University of Bristol, Bristol, United Kingdom. Darryl.J.Hill@bristol.ac.uk
Darryl J
DJ
Hill
Cheryl
C
Whittles
Mumtaz
M
Virji
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D001936:Moraxella catarrhalis / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D045828:Moraxellaceae Infections / Q000382:microbiology; D050506:Mutant Chimeric Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D010033:Otitis Media / Q000382:microbiology; D010802:Phylogeny; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D029424:Pulmonary Disease, Chronic Obstructive / Q000382:microbiology; D011995:Recombination, Genetic; D016415:Sequence Alignment; D014169:Transformation, Bacterial; D019096:Vitronectin / Q000235:genetics / Q000378:metabolism
D015703:Antigens, CD; D001425:Bacterial Outer Membrane Proteins; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D016023:Integrins; D050506:Mutant Chimeric Proteins; C089675:UspA protein, Moraxella catarrhalis; D019096:Vitronectin