Genetic diversity in Treponema pallidum: Implications for pathogenesis, evolution and molecular diagnostics of syphilis and yaws

Abstract

Pathogenic uncultivable treponemes, similar to syphilis-causing Treponema pallidum subspecies pallidum, include T. pallidum ssp. pertenue, T. pallidum ssp. endemicum and Treponema carateum, which cause yaws, bejel and pinta, respectively. Genetic analyses of these pathogens revealed striking similarity among these bacteria and also a high degree of similarity to the rabbit pathogen, T. paraluiscuniculi, a treponeme not infectious to humans. Genome comparisons between pallidum and non-pallidum treponemes revealed genes with potential involvement in human infectivity, whereas comparisons between pallidum and pertenue treponemes identified genes possibly involved in the high invasivity of syphilis treponemes. Genetic variability within syphilis strains is considered as the basis of syphilis molecular epidemiology with potential to detect more virulent strains, whereas genetic variability within a single strain is related to its ability to elude the immune system of the host. Genome analyses also shed light on treponemal evolution and on chromosomal targets for molecular diagnostics of treponemal infections.

A Homology Model Reveals Novel Structural Features and an Immunodominant Surface Loop/Opsonic Target in the Treponema pallidum BamA Ortholog TP_0326

“…Nevertheless, sequence polymorphisms, typically amino acid substitutions resulting from single nucleotide changes, some of which are located in presumptive or proven OMPs, including members of the Tpr family, have been identified (31). Until our study, polymorphisms in a particular OMP had not been related to regions of the protein proven experimentally to be topologically and immunologically relevant.…”

“…Genomic analysis of T. pallidum strains has revealed a remarkably low degree of sequence diversity between T. pallidum strains (31). Nevertheless, sequence polymorphisms, typically amino acid substitutions resulting from single nucleotide changes, some of which are located in presumptive or proven OMPs, including members of the Tpr family, have been identified (31).…”

Transcription of TP0126, Treponema pallidum Putative OmpW Homolog, Is Regulated by the Length of a Homopolymeric Guanosine Repeat

“…Whether phase variation has a role in fostering the ability of T. pallidum to avoid immune clearance, persist, and perhaps adapt to the diverse microenvironments in the host is still unclear. However, evidence that transcription of at least three T. pallidum repeat (tpr) genes encoding putative surface-exposed virulence factors (24,50) is controlled by phase variation (23) strongly suggests that this mechanism is also important in syphilis pathogenesis. A preliminary search for poly(G) sequences (of Ն8 residues) in the Nichols strain genome (24) leads to the identification of 20 such elements that are located upstream or within T. pallidum ORFs (Table 3) and that have been studied only partially or not at all (Table 3).…”

The Endemic Treponematoses

“…pallidum for an outer membrane protein (OMP) involved in attachment to the fibronectin component of the host extracellular matrix; the TPE0488 gene, known to code for a methyl-accepting chemotaxis protein (Mcp); and the recQ helicase gene, which is important in genome maintenance and repair. The TPE0326 gene, which encodes a treponemal ␤-barrel assembly machinery A (BamA) ortholog, and the arp gene, shown to contain a 60-bp repetitive sequence in its central region and to code for a fibronectin-binding protein, were also identified as worthy of further investigation (110,117,118). The arp gene had been previously reported by Harper et al (95) to contain up to four different types of 60-bp repetitive sequences (named types I, II, II-III, and III) in T. pallidum subsp.…”