Phenotypic Effect of IsogenicuspA1anduspA2Mutations onMoraxella catarrhalis035E

Abstract

The UspA surface antigen of Moraxella catarrhalis was recently shown to be comprised of two different proteins (UspA1 and UspA2) which share an internal region containing 140 amino acids with 93% identity (C. Aebi, I. Maciver, J. L. Latimer, L. D. Cope, M. K. Stevens, S. E. Thomas, G. H. McCracken, Jr., and E. J. Hansen, Infect. Immun. 65:4367–4377, 1997). Isogenic uspA1, uspA2, and uspA1 uspA2 mutants were tested in a number of in vitro systems to determine what effect these mutations, either individually or together, might exert on the phenotype of M. catarrhalis 035E. Monoclonal antibodies specific for UspA1 or UspA2 were used in an indirect antibody accessibility assay to prove that both of these proteins were expressed on the surface of M. catarrhalis. All three mutants grew in vitro at the same rate and did not exhibit autoagglutination or hemagglutination properties that were detectably different from those of the wild-type parent strain. When tested for the ability to adhere to human epithelial cells, the wild-type parent strain and the uspA2 mutant readily attached to Chang conjunctival cells. In contrast, theuspA1 mutant and the uspA1 uspA2 double mutant both attached to these epithelial cells at a level nearly 2 orders of magnitude lower than that obtained with the wild-type parent strain, a result which suggested that expression of UspA1 byM. catarrhalis is essential for attachment to these epithelial cells. Both the wild-type parent strain and theuspA1 mutant were resistant to the bactericidal activity of normal human serum, whereas the uspA2 mutant and theuspA1 uspA2 double mutant were readily killed by this serum. This latter result indicated that the presence of UspA2 is essential for expression of serum resistance by M. catarrhalis.

Moraxella catarrhalis induces CEACAM3‐Syk‐CARD9‐dependent activation of human granulocytes

“…burst in infected granulocytes (Sarantis and Gray-Owen, 2012). M. catarrhalis binds to cell surfaces of pulmonary epithelial cells forming multi-cellular, grape-like aggregates and interacts with cell surface receptors (Aebi et al, 1998;Gray-Owen and Blumberg, 2006;Hill and Virji, 2003;Slevogt et al, 2006b;Slevogt et al, 2007;Slevogt et al, 2008). In our study, we found similar M. catarrhalis aggregate formation on human granulocytes.…”

Moraxella catarrhalis is internalized in respiratory epithelial cells by a trigger-like mechanism and initiates a TLR2- and partly NOD1-dependent inflammatory immune response

“…The monoclonal antibody 24B5 was a kind gift of Eric Hansen (University of Texas Southwestern Medical Center, Dallas, TX, USA). The Mab 24B5 specifically binds the ubiquitous surface antigen (UspA1) protein of all M. catarrhalis isolates tested so far (Aebi et al, 1998;Lafontaine et al, 2000).…”

Complement-resistant Moraxella catarrhalis forms a genetically distinct lineage within the species

“…The binding of human vitronectin appears to play an important role in complement resistance of M. catarrhalis [14]. Other surface-exposed factors such as CopB [15], the transferrin-binding protein OMP B1 [16], or the UspA variant called UspA2 [17] have been implicated as important resistance-associated factors. In the present study, 75 strains of M. catarrhalis with di¡erent complement susceptibility phenotypes were collected.…”