Treponema pallidum, the stealth pathogen, changes, but how?
Treponema pallidum rapidly disseminates from a genital site of inoculation to diverse organs where it establishes persistent infection. T. pallidum has 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 the T. pallidum genome with sequence similarity to well-characterized transcription factors is TP0262, an orthologue for cAMP regulatory protein (CRP) of Escherichia coli. Giacani and co-workers identified sequences matching the CRP consensus-binding motif upstream of the promoters of tprE, tprG and tprJ, three members of the T. pallidum repeat (tpr) gene family (subfamily II). Using electrophoretic mobility shift assay, DNaseI footprinting and an E. 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 that T. pallidum has appropriated a paradigmatic global regulator of metabolic processes in heterotrophic bacteria to further its capacity for immune evasion in its obligate human host.
Department of Medicine, University of Connecticut Health Centre, Farmington, CT 06030-3715, USA. JRadolf@up.uchc.edu
Justin D
JD
Radolf
Daniel C
DC
Desrosiers
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D002373:Cyclic AMP Receptor Protein / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D014210:Treponema pallidum / Q000235:genetics* / Q000378:metabolism
D001426:Bacterial Proteins; D002373:Cyclic AMP Receptor Protein