Abstract
Since the recognition of venereal syphilis as a distinct clinical entity in the late 15th century, physicians have marveled at, and been baffled by, its protean manifestations15xTramont, E.C. : 2117–2133See all References15. Unraveling the genetic basis for the remarkable invasiveness and complex tissue tropisms of this bacterium15xTramont, E.C. : 2117–2133See all References15 is the ultimate objective of pathogenesis-related research. Perhaps the greatest disappointment of the genomic sequence is how little insight it provides into the parasitic strategies used by this spirochete. Although T. pallidum does contain open reading frames (ORFs) encoding putative hemolysins/cytotoxins of uncertain pathogenic significance, it does not contain orthologs for any well-known virulence factors. Also lacking are the components of a secretory apparatus, which would be needed to deliver virulence determinants into the host environment. Thus, the sequence confronts us with the realization that the enigma of T. pallidum is actually twofold. It not only points to our need for new physiological paradigms to explain how this unorthodox bacterium copes with the demands of life within a hostile host milieu but it also points to the enormous gaps in our understanding of the distinctive, yet highly successful, brand of human parasitism employed by this bacterium. Many of the solutions to these biological conundrums are likely to reside in the >40% of the genome that consists of functionally uncharacterized genes. The development of experimental strategies to decipher this information and integrate it into a coherent picture will be the new frontier for syphilis research.
Published Version
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