In SilicoScrutiny of Genes Revealing Phylogenetic Congruence with Clinical Prevalence or Tropism Properties ofChlamydia trachomatisStrains

Abstract

Microbes possess a multiplicity of virulence factors that confer them the ability to specifically infect distinct biological niches. Contrary to what is known for other bacteria, for the obligate intracellular human pathogen Chlamydia trachomatis, the knowledge of the molecular basis underlying serovars’ tissue specificity is scarce. We examined all ~900 genes to evaluate the association between individual phylogenies and cell-appetence or ecological success of C. trachomatis strains. Only ~1% of the genes presented a tree topology showing the segregation of all three disease groups (ocular, urogenital, and lymphatic) into three well-supported clades. Approximately 28% of the genes, which include the majority of the genes encoding putative type III secretion system effectors and Inc proteins, present a phylogenetic tree where only lymphogranuloma venereum strains form a clade. Similarly, an exclusive phylogenetic segregation of the most prevalent genital serovars was observed for 61 proteins. Curiously, these serovars are phylogenetically cosegregated with the lymphogranuloma venereum serovars for ~20% of the genes. Some clade-specific pseudogenes were identified (novel findings include the conserved hypothetical protein CT037 and the predicted α-hemolysin CT473), suggesting their putative expendability for the infection of particular niches. Approximately 3.5% of the genes revealed a significant overrepresentation of nonsynonymous mutations, and the majority encode proteins that directly interact with the host. Overall, this in silico scrutiny of genes whose phylogeny is congruent with clinical prevalence or tissue specificity of C. trachomatis strains may constitute an important database of putative targets for future functional studies to evaluate their biological role in chlamydial infections.

Genome expansion in bacteria: the curious case of Chlamydia trachomatis

“…Both Figs. 1 , 2 show that there is a slight division within the urogenital strains (colored green), which is also supported by previous work [ 12 , 16 ]. While pattern differences from trinucleotide frequencies can be observed in Fig.…”

Global survey of mRNA levels and decay rates of Chlamydia trachomatis trachoma and lymphogranuloma venereum biovars

“…On the other hand, the LGV biovar include strains from the serovars L1-L3, which also colonize the host through the ano-urogenital tract, but are able to disseminate to the regional draining lymph nodes, via infection of the macrophages ( Schachter, 1978 ). To date, investigators are struggling to understand which factors underlie the phenotypic differences, namely, discrepancies in growth rates, routes of infection, cell tropism and disease-outcomes ( Gomes et al, 2006 ; Thomson et al, 2008 ; Dehoux et al, 2011 ; Borges et al, 2012 ; Harris et al, 2012 ; Lutter et al, 2012 ; Abdelsamed et al, 2013 ; da Cunha et al, 2014 ; Ferreira et al, 2015 ; and reviewed in Nunes et al, 2013 ). Considering that the genetic dissimilarity among the C. trachomatis strains is less than 2%, it has been speculated that differences in the regulation of gene expression also contribute to the above mentioned phenotypic discrepancies.…”

Chlamydia trachomatisoutbreak: when the virulence-associated genome backbone imports a prevalence-associated major antigen signature

“…We hypothesize that, although the selective advantage of the recombinant strain most likely relies on the novel signature of the hybrid MOMP, the other exchanged genes neighboring ompA (CT677/ rrf , CT678/ pyrH , CT679/ tsf , CT680/ rpsB ), which play key functional roles (ribosome recycling, pyrimidine metabolism, translation elongation and structural ribosome constitution, respectively), may also contribute to an enhanced fitness of this strain. This may be particularly relevant considering that their mutational signature in the hybrid L2b/D-Da strain matches the one observed for prevalent clade T1 strains (i.e., strains with E/F-like genomic backbone) and that the CT677-CT680 region shows phylogenetic signals of tropism and prevalence (Ferreira et al 2014) (Supplemental Figure S2C). For example, it was speculated that increased fitness at or around ompA (preventing recombination) may underlie the expansion of genotype E, which is the most succeeded worldwide genotype among C. trachomatis STIs (Nunes et al 2009; Hadfield et al 2017).…”