TY - JOUR
T1 - Ongoing evolution of Chlamydia trachomatis lymphogranuloma venereum
T2 - exploring the genomic diversity of circulating strains
AU - Seth-Smith, Helena M B
AU - Bénard, Angèle
AU - Bruisten, Sylvia M
AU - Versteeg, Bart
AU - Herrmann, Björn
AU - Kok, Jen
AU - Carter, Ian
AU - Peuchant, Olivia
AU - Bébéar, Cécile
AU - Lewis, David A
AU - Puerta, Teresa
AU - Keše, Darja
AU - Balla, Eszter
AU - Zákoucká, Hana
AU - Rob, Filip
AU - Morré, Servaas A
AU - de Barbeyrac, Bertille
AU - Galán, Juan Carlos
AU - de Vries, Henry J C
AU - Thomson, Nicholas R
AU - Goldenberger, Daniel
AU - Egli, Adrian
N1 - Funding Information:
information J.C.G. was supported by the Instituto de Salud Carlos III (Plan Estatal de I+D+ i 2013–2016), Grant PI16-01242. Acknowledgements Many thanks to Dr Victoria Feher and Professor Rommie Amaro for the original figure of the modelled OmpA, annotated in Fig. 5. Thanks to Dr Alfredo Mari, University of Basel, for help with Fig. S1. Thanks to Prof. Xavier Didelot for assistance with BactDating. We thank Elisabeth Schultheiss for excellent technical assistance in ompA sequencing. Many thanks also to Dr Simon Harris for help with pipeline clarifica-tions, and Dr Madlen Stange and Dr Fanny Wegner for help with selection analysis.
Funding Information:
J.C.G. was supported by the Instituto de Salud Carlos III (Plan Estatal de I+D+ i 2013–2016), Grant PI16-01242.
Publisher Copyright:
© 2021, Microbiology Society. All rights reserved.
PY - 2021/6
Y1 - 2021/6
N2 - Lymphogranuloma venereum (LGV), the invasive infection of the sexually transmissible infection (STI) Chlamydia trachomatis, is caused by strains from the LGV biovar, most commonly represented by ompA-genotypes L2b and L2. We investigated the diversity in LGV samples across an international collection over seven years using typing and genome sequencing. LGV-positive samples (n=321) from eight countries collected between 2011 and 2017 (Spain n=97, Netherlands n=67, Switzerland n=64, Australia n=53, Sweden n=37, Hungary n=31, Czechia n=30, Slovenia n=10) were genotyped for pmpH and ompA variants. All were found to contain the 9 bp insertion in the pmpH gene, previously associated with ompA-genotype L2b. However, analysis of the ompA gene shows ompA-genotype L2b (n=83), ompA-genotype L2 (n=180) and several variants of these (n=52; 12 variant types), as well as other/mixed ompA-genotypes (n=6). To elucidate the genomic diversity, whole genome sequencing (WGS) was performed from selected samples using SureSelect target enrichment, resulting in 42 genomes, covering a diversity of ompA-genotypes and representing most of the countries sampled. A phylogeny of these data clearly shows that these ompA-genotypes derive from an ompA-genotype L2b ancestor, carrying up to eight SNPs per isolate. SNPs within ompA are overrepresented among genomic changes in these samples, each of which results in an amino acid change in the variable domains of OmpA (major outer membrane protein, MOMP). A reversion to ompA-genotype L2 with the L2b genomic backbone is commonly seen. The wide diversity of ompA-genotypes found in these recent LGV samples indicates that this gene is under immunological selection. Our results suggest that the ompA-genotype L2b genomic backbone is the dominant strain circulating and evolving particularly in men who have sex with men (MSM) populations.
AB - Lymphogranuloma venereum (LGV), the invasive infection of the sexually transmissible infection (STI) Chlamydia trachomatis, is caused by strains from the LGV biovar, most commonly represented by ompA-genotypes L2b and L2. We investigated the diversity in LGV samples across an international collection over seven years using typing and genome sequencing. LGV-positive samples (n=321) from eight countries collected between 2011 and 2017 (Spain n=97, Netherlands n=67, Switzerland n=64, Australia n=53, Sweden n=37, Hungary n=31, Czechia n=30, Slovenia n=10) were genotyped for pmpH and ompA variants. All were found to contain the 9 bp insertion in the pmpH gene, previously associated with ompA-genotype L2b. However, analysis of the ompA gene shows ompA-genotype L2b (n=83), ompA-genotype L2 (n=180) and several variants of these (n=52; 12 variant types), as well as other/mixed ompA-genotypes (n=6). To elucidate the genomic diversity, whole genome sequencing (WGS) was performed from selected samples using SureSelect target enrichment, resulting in 42 genomes, covering a diversity of ompA-genotypes and representing most of the countries sampled. A phylogeny of these data clearly shows that these ompA-genotypes derive from an ompA-genotype L2b ancestor, carrying up to eight SNPs per isolate. SNPs within ompA are overrepresented among genomic changes in these samples, each of which results in an amino acid change in the variable domains of OmpA (major outer membrane protein, MOMP). A reversion to ompA-genotype L2 with the L2b genomic backbone is commonly seen. The wide diversity of ompA-genotypes found in these recent LGV samples indicates that this gene is under immunological selection. Our results suggest that the ompA-genotype L2b genomic backbone is the dominant strain circulating and evolving particularly in men who have sex with men (MSM) populations.
KW - Adult
KW - Aged
KW - Australia/epidemiology
KW - Bacterial Outer Membrane Proteins/genetics
KW - Base Sequence
KW - Chlamydia trachomatis/classification
KW - Europe/epidemiology
KW - Evolution, Molecular
KW - Genomics
KW - Genotype
KW - Homosexuality, Male
KW - Humans
KW - Lymphogranuloma Venereum/epidemiology
KW - Male
KW - Middle Aged
KW - Molecular Epidemiology
KW - Phylogeny
KW - Sequence Analysis
KW - Sexual and Gender Minorities
KW - Sexually Transmitted Diseases/microbiology
KW - Whole Genome Sequencing
KW - Young Adult
U2 - 10.1099/mgen.0.000599
DO - 10.1099/mgen.0.000599
M3 - Article
C2 - 34184981
SN - 2057-5858
VL - 7
JO - Microbial Genomics
JF - Microbial Genomics
IS - 6
M1 - 000599
ER -