A Mutation Affecting Expression of a Major Outer Membrane Protein of Moraxella catarrhalis Alters Serum Resistance and Survival In Vivo

Abstract

A major outer membrane protein (CopB) of Moraxella catarrhalis is a target for antibodies that enhance clearance of this organism from the lungs of mice. A mini-Tn10kan transposon was inserted into the cloned copB gene from M. catarrhalis O35E, and an isogenic mutant unable to express the CopB protein was constructed by transforming this mutated gene into the wild-type strain. The mutant grew at the same rate as the wild-type parent strain in broth. Unlike the serum-resistant parent strain, this mutant was sensitive to killing by normal human serum, and its ability to survive and grow in the lungs of animals was impaired. Genetic restoration of CopB protein expression resulted in the simultaneous acquisition of wild-type levels of serum resistance and the ability to resist pulmonary clearance in vivo. Thus, the CopB protein of M. catarrhalis may be important in the interaction between this organism and the defense mechanisms of the respiratory tract.

Lower respiratory tract infection

“…Passive immunization of mice with a monoclonal antibody to OMP B2 enhances pulmonary clearance (83). A mutant which does not express OMP B2 is more sensitive to killing by normal human serum and is more readily cleared from the lungs of mice than is the isogenic parent strain (85). These observations indicate that OMP B2 plays a role in the interaction of B. catarrhalis with host defense mechanisms.…”

“…Table 4 summarizes the features of three animal models of B. catarrhalis infection. A pulmonary clearance model in mice has been used by three laboratories (83,85,113,132,167,174). B. catarrhalis is instilled directly into the lung, and the clearance of viable bacteria from the lung is quantitated.…”

Moraxella (Branhamella) catarrhalis

“…In a murine model, a monoclonal antibody directed towards this OMP enhances clearance of M. catarrhalis from the lung (10). An isogenic mutant which does not express CopB has diminished ability to survive in the same murine pulmonary clearance model (11). This isogenic mutant also has diminished serum resistance to normal human sera in comparison to the wild type strain (11).…”

“…The major OMPs of M. catarrhalis are 98 to 20 kDa in size and have been named A to H (3, 16). In addition, a high-molecular-weight OMP of 300 to 700 kDa has been identified (12,14).CopB, an 81-kDa major OMP, has been a major focus of investigation (1,10,11). This protein is identical to OMP B2 (16, 21).…”

“…CopB, an 81-kDa major OMP, has been a major focus of investigation (1,10,11). This protein is identical to OMP B2 (16, 21).…”