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Chlamydia trachomatis-host cell interactions: role of the chlamydial major outer membrane protein as an adhesin
1Laboratory of Microbial Structure and Function, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840.
Abstract:
The major outer membrane protein (MOMP) of Chlamydia trachomatis is characterized by four symmetrically spaced variable domains (VDs I to IV) whose sequences vary among serotypes. The surface-exposed portions of these VDs contain contiguous sequences that are both serotyping determinants and in vivo target sites for neutralizing antibodies. Previous studies using surface proteolysis of C. trachomatis B implicated VDs II and IV of the MOMP of this serotype in the attachment of chlamydiae to host cells. In this study, we used monoclonal antibodies (MAbs) specific to antigenic determinants located in VDs II and IV of the MOMP of serotype B to further investigate the role of the MOMP in the attachment of chlamydiae to host cells. MABs specific to serotype- and subspecies-specific epitopes located in exposed VDs II and IV, respectively, neutralized chlamydial infectivity for hamster kidney cells by blocking chlamydial attachment. We radioiodinated these MAbs and used them to determine the number and topology of the surface-exposed VDs II and IV epitopes on chlamydial elementary bodies. VDs II and IV each comprised approximately 2.86 x 10(4) negatively charged sites and were in proximity on the chlamydial cell surface. These studies suggest that the MAbs blocked chlamydial attachment by inhibiting electrostatic interactions with host cells. We examined the effects of thermal inactivation on both chlamydial attachment and conformation of the MOMP. Heat-inactivated chlamydiae failed to attach to host cells and exhibited a conformational change in an inaccessible invariant hydrophobic nonapeptide sequence located within VD IV of the MOMPs of C. trachomatis serotypes. These findings suggest that in addition to electrostatic interactions, a common hydrophobic component of the MOMP also contributes to the binding of chlamydiae to host cells. Thus, we propose that the MOMP functions as a chlamydial adhesin by promoting nonspecific (electrostatic and hydrophobic) interactions with host cells. Surface-accessible negatively charged VDs appear to be important in electrostatic binding, while the invariant region of VD IV may provide a subsurface hydrophobic depression which further promotes binding of chlamydiae to host cells through hydrophobic interactions.
Insights
The major outer membrane protein (MOMP) of Chlamydia trachomatis acts as an adhesin, facilitating host cell attachment through both electrostatic and hydrophobic interactions. Monoclonal antibodies targeting variable domains II and IV block this attachment, revealing MOMP
Area of Science:
- Microbiology
- Immunology
- Cell Biology
Background:
- The major outer membrane protein (MOMP) of Chlamydia trachomatis has variable domains (VDs) crucial for serotyping and antibody targeting.
- Previous research implicated VDs II and IV of MOMP in C. trachomatis serotype B attachment to host cells.
Purpose of the Study:
- To investigate the role of MOMP in chlamydial attachment to host cells using serotype-specific monoclonal antibodies (MAbs).
- To elucidate the mechanisms of MOMP-mediated chlamydial adhesion.
Main Methods:
- Utilized MAbs targeting epitopes in VDs II and IV of C. trachomatis serotype B MOMP.
- Employed radioiodinated MAbs to determine epitope number and topology on elementary bodies.
- Examined the effect of thermal inactivation on chlamydial attachment and MOMP conformation.
Main Results:
- MAbs targeting VDs II and IV blocked chlamydial infectivity by inhibiting attachment to host cells.
- VDs II and IV possess numerous negatively charged sites and are located in proximity on the chlamydial surface, suggesting electrostatic interactions.
- Heat inactivation altered MOMP conformation and abolished chlamydial attachment, indicating a role for hydrophobic interactions via an invariant region in VD IV.
Conclusions:
- MOMP functions as a chlamydial adhesin, mediating host cell attachment through both electrostatic and hydrophobic interactions.
- Surface-exposed VDs contribute to electrostatic binding, while an invariant hydrophobic region in VD IV facilitates hydrophobic interactions.
- These findings highlight the multifaceted role of MOMP in chlamydial pathogenesis.