scholarly journals Ongoing evolution of Chlamydia trachomatis lymphogranuloma venereum: exploring the genomic diversity of circulating strains

2021 ◽  
Vol 7 (6) ◽  
Author(s):  
Helena M. B. Seth-Smith ◽  
Angèle Bénard ◽  
Sylvia M. Bruisten ◽  
Bart Versteeg ◽  
Björn Herrmann ◽  
...  
Keyword(s):  
Chlamydia Trachomatis ◽  
Genome Sequencing ◽  
Lymphogranuloma Venereum ◽  
Genomic Diversity ◽  
Invasive Infection ◽  
Content Type ◽  
Genomic Changes ◽  
Variable Domains ◽  
Sex With Men ◽  
Sexually Transmissible Infection

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.

scholarly journals Hypervirulent Chlamydia trachomatis Clinical Strain Is a Recombinant between Lymphogranuloma Venereum (L2) and D Lineages

mBio ◽  
2011 ◽  
Vol 2 (3) ◽  
Author(s):  
Naraporn Somboonna ◽  
Raymond Wan ◽  
David M. Ojcius ◽  
Matthew A. Pettengill ◽  
Sandeep J. Joseph ◽  
...  
Keyword(s):  
Chlamydia Trachomatis ◽  
Virulence Factors ◽  
The United States ◽  
Lymphogranuloma Venereum ◽  
Genetic Exchange ◽  
Clinical Strain ◽  
Toxin Gene ◽  
Content Type ◽  
Hemorrhagic Proctitis ◽  
Sex With Men

ABSTRACTChlamydia trachomatisis an obligate intracellular bacterium that causes a diversity of severe and debilitating diseases worldwide. Sporadic and ongoing outbreaks of lymphogranuloma venereum (LGV) strains among men who have sex with men (MSM) support the need for research on virulence factors associated with these organisms. Previous analyses have been limited to single genes or genomes of laboratory-adapted reference strain L2/434 and outbreak strain L2b/UCH-1/proctitis. We characterized an unusual LGV strain, termed L2c, isolated from an MSM with severe hemorrhagic proctitis. L2c developed nonfusing, grape-like inclusions and a cytotoxic phenotype in culture, unlike the LGV strains described to date. Deep genome sequencing revealed that L2c was a recombinant of L2and D strains with conserved clustered regions of genetic exchange, including a 78-kb region and a partial, yet functional, toxin gene that was lost with prolonged culture. Indels (insertions/deletions) were discovered in anftsKgene promoter and in thetarpandhctBgenes, which encode key proteins involved in replication, inclusion formation, and histone H1-like protein activity, respectively. Analyses suggest that these indels affect gene and/or protein function, supporting thein vitroand disease phenotypes. While recombination has been known to occur forC. trachomatisbased on gene sequence analyses, we provide the first whole-genome evidence for recombination between a virulent, invasive LGV strain and a noninvasive common urogenital strain. Given the lack of a genetic system for producing stableC. trachomatismutants, identifying naturally occurring recombinants can clarify gene function and provide opportunities for discovering avenues for genomic manipulation.IMPORTANCELymphogranuloma venereum (LGV) is a prevalent and debilitating sexually transmitted disease in developing countries, although there are significant ongoing outbreaks in Australia, Europe, and the United States among men who have sex with men (MSM). Relatively little is known about LGV virulence factors, and only two LGV genomes have been sequenced to date. We isolated an LGV strain from an MSM with severe hemorrhagic proctitis that was morphologically unique in tissue culture compared with other LGV strains. Bioinformatic and statistical analyses identified the strain as a recombinant of L2and D strains with highly conserved clustered regions of genetic exchange. The unique culture morphology and, more importantly, disease phenotype could be traced to the genes involved in recombination. The findings have implications for bacterial species evolution and, in the case of ongoing LGV outbreaks, suggest that recombination is a mechanism for strain emergence that results in significant disease pathology.

scholarly journals Whole-Genome Enrichment and Sequencing of Chlamydia trachomatis Directly from Patient Clinical Vaginal and Rectal Swabs

mSphere ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Katherine E. Bowden ◽  
Sandeep J. Joseph ◽  
John C. Cartee ◽  
Noa Ziklo ◽  
Damien Danavall ◽  
...  
Keyword(s):  
Chlamydia Trachomatis ◽  
Intracellular Bacterium ◽  
Genomic Diversity ◽  
Clinical Samples ◽  
Comparative Genomic ◽  
Sexual Networks ◽  
Whole Genome ◽  
Target Enrichment ◽  
Content Type ◽  
Sex With Men

ABSTRACT Chlamydia trachomatis, an obligately intracellular bacterium, is the most prevalent cause of bacterial sexually transmitted infections (STIs) worldwide. Numbers of U.S. infections of the urogenital tract and rectum have increased annually. Because C. trachomatis is not easily cultured, comparative genomic studies are limited, restricting our understanding of strain diversity and emergence among populations globally. While Agilent SureSelectXT target enrichment RNA bait libraries have been developed for whole-genome enrichment and sequencing of C. trachomatis directly from clinical urine, vaginal, conjunctival, and rectal samples, public access to these libraries is not available. We therefore designed an RNA bait library (34,795 120-mer probes based on 85 genomes, versus 33,619 probes using 74 genomes in a previous one) to augment organism sequencing from clinical samples that can be shared with the scientific community, enabling comparison studies. We describe the library and limit of detection for genome copy input, and we present results of 100% efficiency and high-resolution determination of recombination and identical genomes within vaginal-rectal specimen pairs in women. This workflow provides a robust approach for discerning genomic diversity and advancing our understanding of the molecular epidemiology of contemporary C. trachomatis STIs across sample types, geographic populations, sexual networks, and outbreaks associated with proctitis/proctocolitis among women and men who have sex with men. IMPORTANCE Chlamydia trachomatis is an obligate intracellular bacterium that is not easily cultured, which limits our understanding of urogenital and rectal C. trachomatis transmission and impact on morbidity. To provide a publicly available workflow for whole-genome target enrichment and sequencing of C. trachomatis directly from clinical urine, vaginal, conjunctival, and rectal specimens, we developed and report on an RNA bait library to enrich the organism from clinical samples for sequencing. We demonstrate an increased efficiency in the percentage of reads mapping to C. trachomatis and identified recombinant and identical C. trachomatis genomes in paired vaginal-rectal samples from women. Our workflow provides a robust genomic epidemiologic approach to advance our understanding of C. trachomatis strains causing ocular, urogenital, and rectal infections and to explore geo-sexual networks, outbreaks of colorectal infections among women and men who have sex with men, and the role of these strains in morbidity.

scholarly journals Analysis of 721 Chlamydia trachomatis-positive urogenital specimens from men and women using LGV L2-specific real-time PCR assay

2006 ◽  
Vol 11 (42) ◽  
Author(s):  
D Goldenberger ◽  
F Dutly ◽  
M Gebhardt
Keyword(s):  
Chlamydia Trachomatis ◽  
Real Time ◽  
Real Time Pcr ◽  
Western Europe ◽  
Lymphogranuloma Venereum ◽  
Pcr Assay ◽  
Men And Women ◽  
The World ◽  
Sex With Men

The epidemic of rectal lymphogranuloma venereum among men who have sex with men in western Europe and other parts of the world is ongoing

scholarly journals Genome Sequencing of Recent Clinical Chlamydia trachomatis Strains Identifies Loci Associated with Tissue Tropism and Regions of Apparent Recombination

2010 ◽  
Vol 78 (6) ◽  
pp. 2544-2553 ◽  
Author(s):  
Brendan M. Jeffrey ◽  
Robert J. Suchland ◽  
Kelsey L. Quinn ◽  
John R. Davidson ◽  
Walter E. Stamm ◽  
...  
Keyword(s):  
Chlamydia Trachomatis ◽  
Genome Sequencing ◽  
Clinical Presentation ◽  
Tissue Tropism ◽  
Large Collection ◽  
Genome Sequences ◽  
Reading Frame ◽  
Sex With Men ◽  
Relative Prevalence ◽  
Tissue Tropisms

ABSTRACT The human pathogen Chlamydia trachomatis exists as multiple serovariants that have distinct organotropisms for different tissue sites. Culture and epidemiologic data have demonstrated that serovar G is more prevalent, while serovar E is less prevalent, for rectal isolates from men having sex with men (MSM). The relative prevalence of these serovars is the opposite for isolates from female cervical infections. In contrast, the prevalence of serovar J isolates is approximately the same at the different tissue sites, and these isolates are the only C-class strains that are routinely cultured from MSM populations. These correlations led us to hypothesize that polymorphisms in open reading frame (ORF) sequences correlate with the different tissue tropisms of these serovars. To explore this possibility, we sequenced and compared the genomes of clinical anorectal and cervical isolates belonging to serovars E, G, and J and compared these genomes with each other, as well as with a set of previously sequenced genomes. We then used PCR- and restriction digestion-based genotyping assays performed with a large collection of recent clinical isolates to show that polymorphisms in ORFs CT144, CT154, and CT326 were highly associated with rectal tropism in serovar G isolates and that polymorphisms in CT869 and CT870 were associated with tissue tropism across all serovars tested. The genome sequences collected were also used to identify regions of likely recombination in recent clinical strains. This work demonstrated that whole-genome sequencing along with comparative genomics is an effective approach for discovering variable loci in Chlamydia spp. that are associated with clinical presentation.

scholarly journals Lymphogranuloma Venereum in Australia: Anorectal Chlamydia trachomatis Serovar L2b in Men Who Have Sex with Men

2007 ◽  
Vol 45 (3) ◽  
pp. 1029-1031 ◽  
Author(s):  
D. Stark ◽  
S. van Hal ◽  
R. Hillman ◽  
J. Harkness ◽  
D. Marriott
Keyword(s):  
Chlamydia Trachomatis ◽  
Lymphogranuloma Venereum ◽  
Sex With Men

Lymphogranuloma venereum genovariants in men having sex with men in Italy

2020 ◽  
pp. sextrans-2020-054700
Author(s):  
Antonella Marangoni ◽  
Claudio Foschi ◽  
Federico Tartari ◽  
Valeria Gaspari ◽  
Maria Carla Re
Keyword(s):  
Chlamydia Trachomatis ◽  
Lymphogranuloma Venereum ◽  
Hiv Positive ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
High Burden ◽  
Total Prevalence ◽  
Sex With Men ◽  
Reference Strains ◽  
Over Time

ObjectivesLymphogranuloma venereum (LGV) is an STI caused by Chlamydia trachomatis serovars L1-L3. In Europe, the current epidemic is caused mainly by L2b genovariant, although increasing cases associated with other L2 variants have been reported. Here, we assessed the distribution of rectal LGV genovariants among men having sex with men (MSM) in Italy.MethodsFrom 2016 to 2020, all the anorectal swabs collected from MSM attending the STI Clinic of St. Orsola-Malpighi Hospital in Bologna and positive for C. trachomatis were stored. LGV infection was confirmed by a pmpH PCR, and, subsequently, a fragment of the ompA gene was amplified and sequenced. Sequences were aligned to reference strains representing different LGV variants.ResultsLGV cases accounted for one-third of all chlamydial rectal infections with a total prevalence of 4.1% (76/1852). Total number of LGV cases per year remained constant. LGV was mainly found in symptomatic patients (>65%), older than 30 years, with a high burden of other STIs (63.7% HIV-positive, 35.5% with concurrent rectal gonorrhoea, 19.7% with early syphilis). A decreasing trend in HIV-LGV co-infection was noticed over time. Three main LGV genovariants were detected (L2f, 46.1%; L2b, 23.0%; L2-L2b/D-Da, 16.9%), together with other known L2b variants (mainly L2bV2 and L2bV4). Two novel L2b ompA variants with non-synonymous single-nucleotide polymorphisms were found. Over time, the percentage of L2f cases dropped gradually, with a significant increase in L2-L2b/D-Da cases (p=0.04).ConclusionsIn our area, LGV is endemic among MSM with different circulating genovariants. Active surveillance and genotyping programmes are needed to reduce re-establishing of LGV infection.

scholarly journals Asymptomatic Lymphogranuloma Venereum among Nigerian Men who have Sex with Men

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S69-S70
Author(s):  
Trevor Crowell ◽  
Justin Hardick ◽  
Kara Lombardi ◽  
Senate Amusu ◽  
Sunday Odeyemi ◽  
...  
Keyword(s):  
Chlamydia Trachomatis ◽  
Rectal Swab ◽  
Lymphogranuloma Venereum ◽  
Rectal Pain ◽  
Sexually Transmitted ◽  
Oropharyngeal Swab ◽  
Rapid Tests ◽  
Sex With Men ◽  
Incident Cases

Abstract Background Among men who have sex with men (MSM), lymphogranuloma venereum (LGV) has been associated with proctocolitis that can lead to chronic complications and requires a longer course of antibiotic therapy than is recommended for infections due to other serovars of Chlamydia trachomatis (CT). We describe the prevalence and clinical features of LGV among Nigerian MSM diagnosed with anorectal CT. Methods MSM were recruited into the ongoing RV368 cohort in Lagos, Nigeria, using respondent-driven sampling. Participants were screened for HIV and bacterial sexually transmitted infections (STIs) every three months for up to 18 months. HIV was diagnosed using a parallel algorithm of rapid tests on fingerstick blood samples. PCR testing for Neisseria gonorrheae and CTwas performed on voided urine, oropharyngeal swab, and rectal swab specimens. For this analysis, prevalent and incident cases of rectal CT infection underwent additional testing to identify LGV serovars utilizing novel real-time PCR assays specific for the L serovars of CT Chlamydia trachomatis. Results From 28 April 2014–19 July 2016, 420 men underwent screening for rectal STIs, including 66 (15.7%) who had prevalent rectal infection with CT. An additional 68 participants developed incident infections during 208 person-years of follow-up. Of 134 eligible rectal swab specimens, 128 underwent further testing for LGV serovars. Seven (5.5%) of the tested samples were identified as LGV serovars of CT. None of the seven participants with LGV reported any symptoms such as fever or rectal pain. Two of the participants with LGV were simultaneously co-infected with rectal gonorrhea. HIV co-infection was common among participants with both LGV and non-LGV serovars of CT (71% and 77%, respectively, P = 0.74). Conclusion LGV was uncommon but present among Nigerian MSM in this study. LGV needs to be considered even in asymptomatic cases, particularly if anorectal CT infection fails to respond to the usual course of therapy. Consistent screening for L serovars of CT, or empiric treatment for LGV in cases with a high suspicion for this diagnosis, could potentially improve patient outcomes and decrease transmission. Disclosures All authors: No reported disclosures.

scholarly journals Lymphogranuloma Venereum Prevalence in Sweden among Men Who Have Sex with Men and Characterization of Chlamydia trachomatis ompA Genotypes

2006 ◽  
Vol 44 (11) ◽  
pp. 4066-4071 ◽  
Author(s):  
M. Klint ◽  
M. Lofdahl ◽  
C. Ek ◽  
A. Airell ◽  
T. Berglund ◽  
...  
Keyword(s):  
Chlamydia Trachomatis ◽  
Lymphogranuloma Venereum ◽  
Sex With Men
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