Deep comparative genomics among Chlamydia trachomatis lymphogranuloma venereum isolates highlights genes potentially involved in pathoadaptation.
Lymphogranuloma venereum (LGV) is a human sexually transmitted disease caused by the obligate intracellular bacterium Chlamydia trachomatis (serovars L1-L3). LGV clinical manifestations range from severe ulcerative proctitis (anorectal syndrome), primarily caused by the epidemic L2b strains, to painful inguinal lymphadenopathy (the typical LGV bubonic form). Besides potential host-related factors, the differential disease severity and tissue tropism among LGV strains is likely a function of the genetic backbone of the strains. We aimed to characterize the genetic variability among LGV strains as strain- or serovar-specific mutations may underlie phenotypic signatures, and to investigate the mutational events that occurred throughout the pathoadaptation of the epidemic L2b lineage. By analyzing 20 previously published genomes from L1, L2, L2b and L3 strains and two new genomes from L2b strains, we detected 1497 variant sites and about 100 indels, affecting 453 genes and 144 intergenic regions, with 34 genes displaying a clear overrepresentation of nonsynonymous mutations. Effectors and/or type III secretion substrates (almost all of those described in the literature) and inclusion membrane proteins showed amino acid changes that were about fivefold more frequent than silent changes. More than 120 variant sites occurred in plasmid-regulated virulence genes, and 66% yielded amino acid changes. The identified serovar-specific variant sites revealed that the L2b-specific mutations are likely associated with higher fitness and pointed out potential targets for future highly discriminatory diagnostic/typing tests. By evaluating the evolutionary pathway beyond the L2b clonal radiation, we observed that 90.2% of the intra-L2b variant sites occurring in coding regions involve nonsynonymous mutations, where CT456/tarp has been the main target. Considering the progress on C. trachomatis genetic manipulation, this study may constitute an important contribution for prioritizing study targets for functional genomics aiming to dissect the impact of the identified intra-LGV polymorphisms on virulence or tropism dissimilarities among LGV strains.
Reference Laboratory of Bacterial Sexually Transmitted Infections, Department of Infectious Diseases, National Institute of Health, Av. Padre Cruz, 1649-016 Lisbon, Portugal; Bioinformatics Unit, Department of Infectious Diseases, National Institute of Health, Av. Padre Cruz, 1649-016 Lisbon, Portugal.
Vítor
V
Borges
Reference Laboratory of Bacterial Sexually Transmitted Infections, Department of Infectious Diseases, National Institute of Health, Av. Padre Cruz, 1649-016 Lisbon, Portugal; Bioinformatics Unit, Department of Infectious Diseases, National Institute of Health, Av. Padre Cruz, 1649-016 Lisbon, Portugal. Electronic address: j.paulo.gomes@insa.min-saude.pt.
João Paulo
JP
Gomes
D001483:Base Sequence; D002692:Chlamydia trachomatis / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D005798:Genes, Bacterial / Q000235:genetics* / Q000502:physiology; D014644:Genetic Variation / Q000235:genetics; D016680:Genome, Bacterial / Q000235:genetics; D006367:HeLa Cells / Q000382:microbiology; D006801:Humans; D008219:Lymphogranuloma Venereum / Q000382:microbiology*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D016415:Sequence Alignment; D014774:Virulence / Q000235:genetics
Chlamydia trachomatis; Genetic variability; Lymphogranuloma venereum; Pathoadaptation; Proctitis