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Peptide methionine sulfoxide reductase contributes to the maintenance of adhesins in three major pathogens
T M Wizemann1, J Moskovitz, B J Pearce
1Laboratory of Molecular Infectious Diseases, The Rockefeller University, NY 10021, USA.
Abstract:
Pathogenic bacteria rely on adhesins to bind to host tissues. Therefore, the maintenance of the functional properties of these extracellular macromolecules is essential for the pathogenicity of these microorganisms. We report that peptide methionine sulfoxide reductase (MsrA), a repair enzyme, contributes to the maintenance of adhesins in Streptococcus pneumoniae, Neisseria gonorrhoeae, and Escherichia coli. A screen of a library of pneumococcal mutants for loss of adherence uncovered a MsrA mutant with 75% reduced binding to GalNAcbeta1-4Gal containing eukaryotic cell receptors that are present on type II lung cells and vascular endothelial cells. Subsequently, it was shown that an E. coli msrA mutant displayed decreased type I fimbriae-mediated, mannose-dependent, agglutination of erythrocytes. Previous work [Taha, M. K., So, M., Seifert, H. S., Billyard, E. & Marchal, C. (1988) EMBO J. 7, 4367-4378] has shown that mutants with defects in the pilA-pilB locus from N. gonorrhoeae were altered in their production of type IV pili. We show that pneumococcal MsrA and gonococcal PilB expressed in E. coli have MsrA activity. Together these data suggest that MsrA is required for the proper expression or maintenance of functional adhesins on the surfaces of these three major pathogenic bacteria.
Insights
Peptide methionine sulfoxide reductase (MsrA) is crucial for maintaining bacterial adhesins, essential for pathogen attachment. This repair enzyme
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- Pathogenic bacteria utilize adhesins for host tissue attachment, a critical factor in disease.
- Maintaining functional adhesins is vital for bacterial pathogenicity and survival.
Purpose of the Study:
- To investigate the role of peptide methionine sulfoxide reductase (MsrA) in maintaining bacterial adhesins.
- To determine if MsrA impacts the function of adhesins in key pathogenic bacteria.
Main Methods:
- Screening a library of Streptococcus pneumoniae mutants for adherence defects.
- Analyzing Escherichia coli msrA mutants for altered agglutination.
- Assessing MsrA activity in expressed proteins from Neisseria gonorrhoeae.
Main Results:
- A Streptococcus pneumoniae MsrA mutant exhibited a 75% reduction in binding to specific eukaryotic cell receptors.
- Escherichia coli msrA mutants showed decreased mannose-dependent agglutination.
- Pneumococcal MsrA and gonococcal PilB demonstrated MsrA activity when expressed in E. coli.
Conclusions:
- MsrA plays a significant role in the proper expression or maintenance of functional adhesins.
- This finding applies to major pathogenic bacteria including Streptococcus pneumoniae, Neisseria gonorrhoeae, and Escherichia coli.
- MsrA represents a potential target for therapeutic intervention against bacterial infections.