Treponema pallidum, the stealth pathogen, changes, but how?

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Abstract

Treponema pallidumrapidly disseminates from a genital site of inoculation to diverse organs where it establishes persistent infection.T. pallidumhas long been regarded as a stealth pathogen because of its poorly antigenic and non-inflammatory surface. There is now increasing evidence that antigenic variation also contributes to the ability of the spirochaete to evade host defences. Among the small number of proteins encoded by theT. pallidumgenome with sequence similarity to well-characterized transcription factors is TP0262, an orthologue for cAMP regulatory protein (CRP) ofEscherichia coli.Giacani and co-workers identified sequences matching the CRP consensus-binding motif upstream of the promoters oftprE,tprGandtprJ,three members of theT. pallidumrepeat (tpr) gene family (subfamily II). Using electrophoretic mobility shift assay, DNaseI footprinting and anE. coli-based reporter system, they demonstrated that TP0262 specifically recognizes the putative binding sequences and that DNA binding is cAMP-dependent. Their report, a major methodological advance for syphilis research, suggests thatT. pallidumhas appropriated a paradigmatic global regulator of metabolic processes in heterotrophic bacteria to further its capacity for immune evasion in its obligate human host.

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