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Treponema pallidum and the quest for outer membrane proteins
1Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-9113, USA.
Abstract:
Treponema pallidum, the syphilis spirochaete, has a remarkable ability to evade the humoral and cellular responses it elicits in infected hosts. Although formerly attributed to the presence of an outer coat comprised of serum proteins and/or mucopolysaccharides, current evidence indicates that the immuno-evasiveness of this bacterium is largely the result of its unusual molecular architecture. Based upon a combination of molecular, biochemical, and ultrastructural data, it is now believed that the T. pallidum outer membrane (OM) contains a paucity of poorly immunogenic transmembrane proteins ('rare outer membrane proteins') and that its highly immunogenic proteins are lipoproteins anchored predominantly to the periplasmic leaflet of the cytoplasmic membrane. The presence in the T. pallidum OM of a limited number of transmembrane proteins has profound implications for understanding syphilis pathogenesis as well as treponemal physiology. Two major strategies for molecular characterization of rare outer membrane proteins have evolved. The first involves the identification of candidate OM proteins as fusions with Escherichia coli alkaline phosphatase. The second involves the characterization of candidate OM proteins identified in outer membranes isolated from virulent T. pallidum. Criteria to define candidate OM proteins and for definitive identification of rare OM proteins are proposed as a guide for future studies.
Insights
Treponema pallidum evades immune responses due to its unique outer membrane (OM) structure, featuring rare, poorly immunogenic transmembrane proteins. This molecular architecture is key to understanding syphilis pathogenesis and treponemal physiology.
Area of Science:
- Microbiology
- Immunology
- Pathogenesis
Background:
- * Treponema pallidum, the causative agent of syphilis, exhibits significant immune evasion capabilities.
- * Previous theories attributed this to an outer coat, but current evidence points to molecular architecture.
- * Understanding this architecture is crucial for syphilis pathogenesis and treponemal physiology.
Purpose of the Study:
- * To elucidate the molecular basis of Treponema pallidum's immune evasion.
- * To characterize the rare outer membrane proteins (OMPs) of T. pallidum.
- * To propose criteria for identifying T. pallidum OMPs.
Main Methods:
- * Analysis of molecular, biochemical, and ultrastructural data.
- * Identification of candidate OMPs using Escherichia coli alkaline phosphatase fusions.
- * Characterization of OMPs from isolated virulent T. pallidum outer membranes.
Main Results:
- * T. pallidum's outer membrane (OM) has few, poorly immunogenic transmembrane proteins (rare OMPs).
- * Highly immunogenic proteins are lipoproteins in the cytoplasmic membrane's periplasmic leaflet.
- * Two strategies for molecular characterization of rare OMPs have been developed.
Conclusions:
- * The paucity of transmembrane proteins in the T. pallidum OM is central to its immune evasion.
- * This finding has significant implications for syphilis pathogenesis and treponemal physiology.
- * Defined criteria are proposed for future identification of rare T. pallidum OMPs.