Phylogenetic Analysis ofChlamydia trachomatisTarp and Correlation with Clinical Phenotype

Abstract

Chlamydia trachomatis is the leading cause of infectious blindness worldwide and is the most commonly reported pathogen causing sexually transmitted infections. Tarp (translocated actin recruiting phosphoprotein), a type III secreted effector that mediates actin nucleation, is central to C. trachomatis infection. The phylogenetic analysis of tarP from reference strains as well as ocular, genital, and lymphogranuloma venereum (LGV) clinical isolates demonstrated an evolutionary relationship with disease phenotype, with LGV and ocular isolates branched into clades that were separate from the urogenital isolates. The sequence analysis of Tarp indicated a high degree of variability and identified trends within clinical groupings. Tarps from LGV strains contained the highest number of tyrosine-rich repeat regions (up to nine) and the fewest (two) predicted actin binding domains. The converse was noted for Tarp proteins from ocular isolates that contained up to four actin binding domains and as few as one tyrosine-rich repeat region. The results suggest that Tarp is among the few known genes to play a role in C. trachomatis adaptations to specific niches within the host.

Polymorphisms in Inc Proteins and Differential Expression ofincGenes among Chlamydia trachomatis Strains Correlate with Invasiveness and Tropism of Lymphogranuloma Venereum Isolates

“…However, it must be clarified that other proteins in addition to Inc proteins are likely involved in the specificity of infection by LGV strains (8,30). Moreover, the overall determinants of tissue tropism of C. trachomatis should be complex and multifactorial and should certainly also include, e.g., the products of the trpRBA operon (10,19,51) or of the cytotoxin gene (11) and Tarp (34).…”

“…On the other hand, Inc proteins that could manipulate intracellular membrane trafficking, such as those that have SNARE-like motifs (CT119/IncA, CT223, and CT813) (17) or interact with Rab GTPases (CT229) (46), are good candidates to selectively inhibit macrophage phagolysosomal fusion. Not all C. trachomatis Inc proteins tentatively proposed to be specifically involved in inhibiting phagolysosomal fusion have homologues in other chlamydial species, which also avoid this host cell degradation pathway (16,34). It is possible that each chlamydial species evolved particular Inc proteins, and other virulence proteins, to account for the specificity of each type of cell it infects.…”

“…Therefore, the determinants of the different types of infection (invasive or noninvasive) and tissue tropism (eyes, genitals, and lymph nodes) must rely on the few genes present in some strains but not in others and on nucleotide differences which may lead either to proteins with disease group-specific amino acids or to differential gene expression. Some of these determinants were suggested in previous studies: the tryptophan (trpRBA) operon (10,19,51) and genes encoding cytotoxin (11), phospholipase (40), polymorphic membrane proteins (Pmps) (24), and Tarp (34).…”

The AlternativeTranslational Profile That Underlies the Immune-Evasive State of Persistence in Chlamydiaceae Exploits Differential Tryptophan Contents of the Protein Repertoire

“…Tarp functions as a multivalent phosphorylation-dependent signaling hub that is crucial for success in the early phase of chlamydial infection (27) and was recently shown to interact with the human adaptor protein SHC1 (85). Variations in chlamydial Tarp exhibit interesting correlations with particular variations of clinical phenotype (76). Given the biology of the persistent state, one would not expect Tarp to be competent for export during persistence and the attending Trp limitation.…”

Insights into the Biology, Infections and Laboratory Diagnosis of Chlamydia

“…The results suggest that Tarp is among the few genes to play a role in adaptations to specific niches in the host. 58 …”