Graphical Abstract
We describe a new lineage of Chlamydia trachomatis lymphogranuloma venereum identified in Argentina, carrying ompA-genotype L4. We also present further diversification of the globally circulating L2b lineage.
Keywords: L2b, Phylogeny, STI, whole genome sequencing
Abstract
Whole-genome analysis has provided insights into the evolution of Chlamydia trachomatis and, recently, into circulating strains that cause lymphogranuloma venereum (LGV). A large LGV outbreak of a new ompA-genotype, L2b, was first reported in Europe in the early 2000s, primarily affecting men who have sex with men (MSM), and then expanded globally. More recent work shows that this outbreak is diversifying into variants of described ompA-genotypes, with the same L2b genomic backbone. This study extends the investigation of LGV cases to Argentina and Finland. In 2017, an LGV outbreak was described in Argentina characterized by distinct genomic features shown by both ompA-genotyping and Multi-Locus Sequence Typing (MLST) analysis. We have obtained whole-genome sequences from cultured isolates and clinical samples via SureSelect (Agilent) target enrichment. Based on ompA and phylogenetic analyses, we describe further diversity within the ompA-genotype L2b clade, illustrating the transmission dynamics in Argentina and Finland. A key finding is that of a novel clade of Argentinian samples, characterized by a proposed new ompA-genotype L4. Additionally, we present the genome sequence of a non-LGV strain associated with anorectal proctitis. These findings contribute to the investigation of LGV evolution, particularly with the presence of the novel L4 lineage, and provide insights into genomic diversity and transmission dynamics of C. trachomatis.
Impact Statement
The phylogeny of Chlamydia trachomatis has been described in several publications and has been clear for a decade. The evolution of this sexually transmitted infection in the intervening years also informs a great deal about the transmission opportunities and selective pressures that the intracellular bacterium is under. Through genome sequencing, also directly from clinical samples, we provide the first lymphogranuloma venereum (LGV) genomes from Argentina and Finland and describe further evidence of global circulation of the ompA-genotype L2b lineage. We describe a fully novel lineage of LGV C. trachomatis, from Argentina, proposed as ompA-genotype L4. We also find evidence of a strain causing proctitis from the urogenital lineage. Together, these provide significant new findings in the investigation of C. trachomatis.
Data Summary
All Illumina sequence data, with human read data removed using Hostile [1] and KrakenTools (https://github.com/jenniferlu717/KrakenTools), are deposited with the European Nucleotide Archive under project number PRJEB72167 with the accession numbers given in Table S1. The Supplementary Material can be found at https://doi.org/10.6084/m9.figshare.28131641.v1 [2].
Introduction
The sexually transmitted infection (STI)-causing bacterium Chlamydia trachomatis has an invasive biovar, lymphogranuloma venereum (LGV), which causes LGV, as well as the urogenital (UG) and ocular biovars. Recently, interest has arisen around the current evolution of LGV strains of C. trachomatis [3,5]. Whole-genome sequencing is the best method to further investigate globally circulating strains of C. trachomatis LGV.
The most recent genomic findings on LGV C. trachomatis showed ongoing evolution of the ompA-L2b lineage, with the few genomic SNPs found over-represented in the ompA gene, generating novel variations in the encoded Major Outer Membrane Protein (MOMP) protein [3].
Comprehensive nationwide prevalence data for C. trachomatis are lacking in Argentina, as is the identification of all LGV cases; however, the limited data suggest higher rates of LGV in Buenos Aires than in Europe [6,8]. Since 2017, proctitis patients in Buenos Aires, mostly Human Immunodeficiency Virus (HIV)-infected MSM, have been screened for C. trachomatis [9], showing a range of ompA-genotypes [10] and MLST types [11].
This work further investigates LGV genomes from Argentina and Finland in the context of global data to broaden the spectrum of LGV genomes analysed to date. We show further developments in the ompA-genotype L2b lineage, confirm the genomic separation of a new South American lineage, termed ompA-genotype L4, and describe the context of a rectally derived UG lineage strain.
Methods
Sample collection, culture and DNA extraction
Rectal swab samples were obtained from symptomatic adult patients presenting proctitis-compatible symptoms and STI risk factors between September 2017 and August 2023, attending a public hospital and a private clinic in Buenos Aires, Argentina (Hospital Juan A. Fernández and Centro Privado de Cirugía y Coloproctología). Additionally, rectal swab samples from symptomatic patients and those with partner notifications attending the outpatient STI clinic at the Helsinki University Central Hospital in Finland between 2011 and 2013 were collected from MSM with symptoms suggestive of LGV or due to partner notification. These samples were either cultured or had DNA extracted as described in [12].
Sequencing
Genomic sequencing data were obtained either from cultured samples or via SureSelect target enrichment (Agilent) (Table S1). Methods were performed as described in [12]. Briefly, target enrichment was performed on clinical samples with SureSelect XT HS2 DNA with post-capture pooling for Illumina Platform NGS (G9983-90500 Rev A0, Agilent SureSelect), using baits designed to cover all diversity of C. trachomatis using Design ID S3465202 and Design ID S3465164. Samples were sequenced PE150 on Illumina MiSeq or NextSeq1000 platforms.
Sequence analysis
Reads were trimmed with trimmomatic v0.39 [13]. Mapping to reference AM884177, base calling and generation of multiple sequence alignments used snippy v4.6.0 (https://github.com/tseemann/snippy) with default parameters, except a minimum coverage of 5 to enable calling from regions of lower read depth, and with the rRNA operons masked. Genomes were considered acceptably complete when the percentage of genome covered was >95%, the mean read depth was >10 and <20% Ns were called at <0–5× read depth. The presence of more than one strain of C. trachomatis in all samples was analysed using the R package vcfR [14] by looking at all minority variants with a minimum frequency of 10% and a minimum depth of 5. All were found to have fewer than 200 minority variants and are thus considered pure strains.
Phylogenies were created using all LGV genome data available [3,15, 16] in IQtree v2.2.0.3 [17] with 1000 ultrafast bootstraps. Gubbins v3.3.0 [18] was used to remove recombinations, with five iterations, 1000 bootstraps, iqtree-fast as first-tree-builder, iqtree as tree-builder and custom model K3Pu+F+I+I+R3. FastBAPS was used to define clades (https://github.com/gtonkinhill/fastbaps). UG phylogenies were built by comparing with previous UG genomes and mapping against the genome of E/Bour (HE601870) [15]. Phylogenies were visualized with associated metadata in Phandango [19]. The whole-genome alignments are given in Files S1 and S2 available in the online Supplementary Material.
Complete coding sequences (CDSs) of ompA were extracted from the mapped alignments and compared with capillary sequence data [11] and blastn results from the National Center for Biotechnology Information (NCBI) database (https://blast.ncbi.nlm.nih.gov/Blast.cgi?) in AliView v1.27 [20] (Table S1).
Statistical analysis
Statistical analysis of patient data was performed using InfoStat software version 2020, Universidad Nacional de Córdoba, Córdoba, Argentina. The two-tailed Fisher exact test was used for categorical variable analysis. Statistical significance was defined as P<0.05.
Results and discussion
Phylogeny of C. trachomatis LGV genomes
C. trachomatis LGV genomes (n=32 from Argentina and n=9 from Finland) were obtained following either culture (n=10 from Argentina and n=9 from Finland) or SureSelect (n=22 from Argentina, one of which had been cultured but required target enrichment to produce a full genome) and Illumina sequencing. These are the first genomes from Argentinian and Finnish LGV strains. The genomes were compared phylogenetically with previously published LGV genomes (Fig. 1). A phylogeny with duplicate samples (n=8), showing the reproducibility of the SureSelect method, is given in Fig. S1, and the recombinations identified within the LGV genomes are shown in Fig. S2.
Fig. 1. Recombination-adjusted phylogeny of LGV strains from Argentina, Finland and previous publications. All published LGV genomes with available data were included in the analysis. The right of the phylogeny is relevant metadata: duplicate patient samples, Bayesian Analysis of Population Structure (BAPS) cluster (clade, with the polyphyletic BAPS cluster 6 representing the genetic diversity of the population), genome method (data for this paper), ompA-genotype, country and year as described in the key to the top left. Missing data are displayed as white. Names of genomes from this publication are coloured in light blue for Argentina and dark blue for Finland in the phylogeny. Bootstrap values from 1000 ultrafast bootstraps are shown as percentages on major branches.
Further global circulation of the ompA-genotype L2b lineage
Many (n=21/32) of the Argentinian samples and all the Finnish samples (n=9) fall within the ompA-genotype L2b clade (BAPS cluster 5 in Fig. 1). The samples within this L2b clade show diverse ompA-genotypes even over short time spans, suggesting selective pressure on the encoded MOMP protein. Several sub-clades are apparent, with six separate locations of the Finnish samples in the phylogeny speaking for European circulation of many strains. Three pairs of samples represent the possible local circulation of strains in Helsinki: these are unlikely to be from direct partners or through partner notifications due to disparate sampling dates.
The closely related groups of two to six genomes from Argentinian samples suggest locally circulating strains among the MSM community in Buenos Aires. One patient had two genomically identical samples from two different locations (an abscess and an anorectal swab), both being ompA-genotype L2 within the L2b clade. It is worth noting that the other samples in sub-clades were independent and, based on the patients’ histories, were likely not connected. These groups are often closely related to samples from Europe, indicating multiple importations of strains from diverse international sources. As these are the most recent samples in the phylogeny, ongoing travel is not yet apparent. Of note, two Argentinian samples from 2017 and 2023, respectively, carry identical genomes to several European samples, including L2b/UCH1 and L2b/UCH2 from 2006, reiterating that C. trachomatis has a less clock-like mutation rate than other bacterial species [15]. The L2b clade is clearly highly international, reflecting a global circulating lineage of C. trachomatis LGV.
Complete genomes were obtained from two samples carrying new ompA variants (L2i and L2bv12) recently described in Argentina [11]: the ompA variant L2i, carrying a mutation that leads to an S162I substitution at the site that differentiates ompA-genotypes L2 and L2b, and L2bv12, carrying a mutation that leads to the S164D substitution, both in the variable domain (VD)2.
Description of novel lineage from Argentina
We identified a new lineage comprising 11 Argentinian samples. This separate clade (BAPS cluster 4 in Fig. 1) is defined by a branch of >200 SNPs and is confirmed as a separate genetic cluster. Of interest, one patient had two samples taken over time: ompA-genotype L4 from April 2018 and ompA-genotype L2 within the L2b clade from August 2018, suggesting reinfection with a different strain after treatment (Fig. 1).
The ompA gene of the L4 clade is most similar to that of ompA-genotype L1 (accession HE601950.1), but with ten nucleotide substitutions; two versions of ompA-genotype L4 (L4 and L4v1) vary by a single SNP [11] (Table S1). The amino acid substitutions compared with ompA-genotype L1 are all located in VDs: A90T in VD1, N162S in VD2 and T311A in VD4. Taking into account this level of diversity from all previously described LGV genomes and the number of samples defining the clade (n=11), we propose the new ompA-genotype L4.
This novel lineage shows a tight sub-clade of strains presumably representing an ongoing outbreak, with a more distantly related member also represented towards the root of the clade, showing the diversity present in the Buenos Aires area. There is likely to be further unsampled diversity within this clade, perhaps with more diverse members of this clade in other areas of South America. The lineage also appears to be present in France [21]: genomics could here give insights into the origins of this lineage.
Clinical relevance of ompA-genotype L4 lineage
Comparative analysis of the clinical data between the patients in clades L2b and L4 shows differences in the frequencies of some factors, although without statistical significance (Table 1). The presence of an anorectal inflammatory tumour was higher in patients infected with LGV from the ompA-genotype L4 clade (50% compared with 25% in the ompA-genotype L2b clade). The presence of anal ulcers was more frequent in patients infected with LGV from the ompA-genotype L2b clade (55% compared with 22% in the ompA-genotype L4 clade), and the presence of other concomitant STIs in addition to HIV was higher in LGV from the ompA-genotype L2b clade (50% compared with 30% in the ompA-genotype L4 clade). However, the number of cases analysed is too low to draw meaningful conclusions.
Table 1. Clinical data of patients from Buenos Aires. Comparison of symptoms between LGV from clades ompA-genotype L2b and ompA-genotype L4.
| Sample | LGV clade | Rectal syndrome* | Anal ulceration† | Severity of proctitis | Inguinallymphadenopathy | Tumour‡ | HIV | Other STI |
|---|---|---|---|---|---|---|---|---|
| M010179RR | L4 | + | − | Moderate | − | − | + | − |
| M030991JA | L4 | + | − | Moderate | + | Anorectal | + | GC/HPV/TP |
| M040989RG | L4 | + | − | Severe | + | Anorectal | + | − |
| M051286CN | L4 | + | + | Moderate | − | − | − | HSV |
| M210393MB | L4 | + | − | Moderate | + | Anorectal | + | − |
| M211085WM | L4 | + | − | Not verified§ / | − | − | − | − |
| M250688ME | L4 | + | + | Mild | + | Anorectal | + | − |
| M251089VL | L4 | + | − | Moderate | + | − | + | − |
| M260278JB | L4 | + | − | Severe | + | Anorectal | + | TP |
| M280389NL | L4 | + | nd | Moderate | + | − | + | − |
| M030791PE | L2b | + | + | Severe | + | − | + | TP/HPV |
| M030991JA-BIS | L2b | + | − | Moderate | + | Anorectal | + | NG/TP/HPV |
| M040486LC | L2b | + | − | Moderate | − | − | + | − |
| M041079DP | L2b | − | + | Not verified§ | + | nd | + | − |
| M071289JM | L2b | nd | + | Mild | − | − | + | − |
| M090190LL | L2b | + | + | Moderate | + | − | + | TP |
| M140182AO | L2b | + | − | Moderate | − | − | − | − |
| M150261JR | L2b | − | − | Moderate | − | − | + | NG/HPV |
| M150291EC | L2b | + | + | Severe | − | − | + | − |
| M161182LR | L2b | + | − | Moderate | + | − | + | − |
| M170285JP | L2b | + | − | Moderate | + | − | + | HPV/HSV |
| M200197AC | L2b | + | − | Mild | + | Anorectal | + | NG/TP/HSV |
| M210970DM | L2b | + | − | Severe | + | − | + | − |
| M220485JT | L2b | + | + | Moderate | − | − | + | − |
| M221189LM | L2b | + | − | Moderate | + | − | + | NG |
| M230381AR | L2b | + | + | Moderate | + | − | − | − |
| M230574JM | L2b | + | + | Severe | − | − | + | − |
| M231186AM | L2b | + | + | Severe | + | Anorectal | + | NG |
| M270381MC | L2b | + | + | Not verified§ | + | Endoanal | + | HPV |
| M281284MA | L2b | − | + | Severe | − | Perianal | + | TP |
| P-value L4/L2b | 0.15 | 0.11 | 0.82 | 0.55 | 0.12 | 0.65 | 0.26 |
Rectal syndrome is characterized by rectal discharge, pushing and tenesmus.
Ulcers located in the anal region.
A mass located around the anal area
Not verified, as rectoscopy was not performed.
nd, Not done.
HPV, human papillomavirus; HSV, herpes simplex virus; NG, Neisseria gonorrhoeae; TP, Treponema pallidum.
Urogenital T1 lineage sample causing proctitis
One sample from Argentina falls within the UG T1 lineage, as described by Hadfield et al. [15] (Fig. 2). Sample M160595IY is located at the base of a clade of diverse genomes from diverse countries. Sample M160595IY was identified as ompA-genotype D by RFLP, and from Whole Genome Sequencing (WGS), it is 1 bp (synonymous SNP at amino acid 212) from other described D strains (Table S1). This branch is also defined by several recombination events, covering the same loci that are often affected by recombination in the T1 lineage strains (data not shown).
Fig. 2. Recombination-adjusted phylogeny of UG strains belonging to lineage T1 [15] showing the location of sample M160595IY from Argentina in the context of those from previous publications. The tree is rooted according to [15]. The right of the phylogeny is relevant metadata: ompA-genotype, country and year as described in the key to the far right. The name of the genome from this publication is pale blue in the phylogeny. The bootstrap of 92% from 1000 ultrafast bootstraps is shown on the branch of interest.
Sample M160595IY was taken from a young man presenting with symptoms of mucorrhoea, proctalgia and tenesmus, which had been developing for a month prior to the medical consultation. Diagnosis revealed mild proctitis. The patient’s sexual practices include both receptive and insertive anal sex, as well as oro-anal sex, with a reported 20 sexual partners in the previous 12 months. The patient did not present any other bacterial STI coinfections at the time of symptom onset and responded to the antimicrobial treatment. That the genome derives from an anorectal swab from a patient with proctitis, with no evidence of a mixed infection with an LGV strain in the sample, suggests that this UG strain was the cause of mild proctitis.
Genome sequences from ompA-genotypes E, G and Ja isolated from rectal swabs have previously been published [22,23], and non-LGV genotypes causing proctitis in patients have been identified through ompA-genotyping [7,24]. Additionally, recombinant LGV/UG strains have been identified in the past [4,25, 26]; however, in this case, we see a genome with ompA-genotype D in a UG genomic backbone isolated from an anorectal swab from a male patient with proctitis. This is the first genome sequenced from a symptomatic proctitis case caused by a non-recombinant ompA-genotype D isolate [7,22,24]. A deeper investigation into such samples may lead to the identification of genomic regions involved in rectal tropism.
Plasmid analysis
Plasmids from the new strains were also analysed in the context of previously published data. Among the LGV plasmids, there is very little diversity, and the plasmid is highly conserved. All the plasmids from the novel ompA-genotype L4 clade are located very closely in the phylogeny, with the plasmids from L1/440, L2/514BU11 and L2/526BU5, all from the USA and isolated in 1968 (Fig. S3A). This could indicate plasmid exchange between ompA-genotypes within the Americas, although further data would be required to confirm this. While the plasmids of many strains within the ompA-genotype L2b clade are almost identical to that in L2b/UCH2, one plasmid (from sample M230574JM) stands out for having a single, synonymous SNP in plasmid coding sequence CDS1.
The plasmid from the UG strain M160595IY is located in the phylogeny close to many plasmids from ompA-genotypes D, E, F and J (Fig. S3B). It carries three additional SNPs, representing synonymous mutations in CDS1 and CDS8, and R324I in CDS3. This would be consistent with the genomic phylogenetic position.
Conclusions
This study demonstrates the widespread global distribution of the genomic clade of ompA-genotype L2b, its success as the primary causative agent of LGV and the recently evolved diversity within the clade. It confirms that in locations distant from the most studied European part of the outbreak such as Argentina, strains identified as L2 by ompA-genotyping also present the genetic backbone of ompA-genotype L2b. Our data suggest that in Buenos Aires, there have been multiple introduction events of this ompA-genotype L2b clade.
We also present a complete genome of a non-LGV ompA-genotype D sample causing proctitis, confirming their UG genomic backbone. This highlights the fact that some non-LGV strains can cause proctitis that in some cases is symptomatically similar to that produced by LGV strains.
A further key finding is the detection of a new clade causing LGV in Buenos Aires, which is vastly different from the previously described lineages, leading us to propose its designation as ompA-genotype L4. Future studies will further investigate the diversity within this clade and the association of the new ompA-genotype L4 clade with possible specific clinical manifestations.
Supplementary material
Acknowledgements
We thank Daniel Gander, Valéria Pires and Stefan Antener (all UZH) for their excellent technical assistance with sequencing. We also thank Dr Osvaldo Degregorio (UBA) for his collaboration in the statistical analysis. Many thanks to Sofia Polcowñuk for designing the graphical abstract.
Abbreviations
- BAPS
bayesian analysis of population structure
- HIV
human immunodeficiency virus
- LGV
lymphogranuloma venereum
- MLST
multi-locus sequence typing
- MOMP
major outer membrane protein
- MSM
men who have sex with men
- NCBI
National Center for Biotechnology Information
- STI
sexually transmitted infection
- UG
urogenital
Footnotes
Funding: This work was supported by the STIDirect Grant to HMBSS from the Gottfried und Julia Bangerter-Rhyner-Stiftung and the Universidad de Buenos Aires, UBACyT, grant number UBACYT 20020150100223BA and UBACYT 20020190100357BA.
Author contributions: K.A.B.: Investigation, Data curation, Formal analysis, Methodology, Visualization, Writing – original draft; F.W.: Investigation, Data curation, Formal analysis, Visualization; V.B.: Investigation; A.C.E.: Resources; M.L.G.V.: Resources; D.L.A.: Resources; L.L.R.: Resources; L.S.L.: Resources; M.H.P.: Resources; E.H.-B.: Resources; F.I.: Resources, Investigation; A.E.: Resources, Writing – review and editing; H.M.B.S.-S.: Data curation, Funding acquisition, Methodology, Project administration, Supervision, Validation, Writing – original draft; M.R.F.: Conceptualization, Funding acquisition, Project administration, Writing – review and editing.
Ethical statement: The study on Argentinian samples was approved by an Ethics Committee (‘Detección de C. trachomatis en pacientes con rectitis infecciosa: prevalencia y tipificación’, Gobierno de la Ciudad de Buenos Aires, no. 201723) and patients provided written informed consent. The Finnish samples are de-identified, and the data are anonymized; therefore, no specific ethical approval is required.
Contributor Information
Karina Andrea Büttner, Email: karina.buttner@gmail.com.
Fanny Wegner, Email: fwegner@imm.uzh.ch.
Vera Bregy, Email: vbregy@imm.uzh.ch.
Andrea Carolina Entrocassi, Email: carolinaentrocassi@gmail.com.
María Lucía Gallo Vaulet, Email: lgvaulet@ffyb.uba.ar.
Deysi López Aquino, Email: lopezdeysi20@gmail.com.
Luciana La Rosa, Email: lucianalarosa@gmail.com.
Laura Svidler López, Email: lausvidlerlopez@gmail.com.
Mirja H. Puolakkainen, Email: Puolamirja.puolakkainen@helsinki.fi.
Eija Hiltunen-Back, Email: eija.hiltunen-back@hus.fi.
Frank Imkamp, Email: imkamp@imm.uzh.ch.
Adrian Egli, Email: aegli@imm.uzh.ch.
Helena M.B. Seth-Smith, Email: hsethsmith@imm.uzh.ch.
Marcelo Rodríguez Fermepin, Email: mrfchlam@ffyb.uba.ar.
References
- 1.Constantinides B, Hunt M, Crook DW. Hostile: accurate decontamination of microbial host sequences. Bioinformatics. 2023;39:btad728. doi: 10.1093/bioinformatics/btad728. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Andrea Büttner K, Wegner F, Vera B, Entrocassi AC, Gallo Vaulet ML, et al. 2025. Chlamydia trachomatis genomes from rectal samples: description of new clade comprising ompA-genotype L4 from Argentina. Figshare. Dataset . [DOI] [PMC free article] [PubMed]
- 3.Seth-Smith HMB, Bénard A, Bruisten SM, Versteeg B, Herrmann B, et al. Ongoing evolution of Chlamydia trachomatis lymphogranuloma venereum: exploring the genomic diversity of circulating strains. Microb Genom. 2021;7:000599. doi: 10.1099/mgen.0.000599. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Borges V, Cordeiro D, Salas AI, Lodhia Z, Correia C, et al. Chlamydia trachomatis: when the virulence-associated genome backbone imports a prevalence-associated major antigen signature. Microb Genom. 2019;5:e000313. doi: 10.1099/mgen.0.000313. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Peuchant O, Touati A, Sperandio C, Hénin N, Laurier-Nadalié C, et al. Changing pattern of Chlamydia trachomatis strains in lymphogranuloma venereum outbreak, France, 2010-2015. Emerg Infect Dis. 2016;22:1945–1947. doi: 10.3201/eid2211.160247. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Ministerio de Salud. Presidencia de la Nación.Argentina Boletín No 39: Respuesta al VIH y las ITS en la Argentina [Internet] 2022. [4-February-2024]. https://bancos.salud.gob.ar/recurso/boletin-ndeg-39-respuesta-al-vih-y-las-its-en-la-argentina accessed.
- 7.La Rosa L, Svidler López L, Entrocassi AC, López Aquino D, Caffarena D, et al. Chlamydia trachomatis anorectal infections by LGV (L1, L2 and L2b) and non-LGV serotypes in symptomatic patients in Buenos Aires, Argentina. Int J STD AIDS. 2021;32:1318–1325. doi: 10.1177/09564624211038384. [DOI] [PubMed] [Google Scholar]
- 8.ECDC . European Centre for Disease Prevention and Control; 2022. Lymphogranuloma venereum - Annual Epidemiological Report for 2019 [Internet]https://www.ecdc.europa.eu/sites/default/files/documents/lymphogranuloma-venereum-annual-epidemiological-report-2019.pdf [Google Scholar]
- 9.López LS, La Rosa L, Entrocassi AC, Caffarena D, Santos B, et al. Rectal lymphogranuloma venereum, Buenos Aires, Argentina. Emerg Infect Dis. 2019;25:598–599. doi: 10.3201/eid2503.180600. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Fermepin MR, Entrocassi AC, Büttner KA, Caffarena D, Aquino DL, et al. More than L2b in rectal lymphogranuloma venereum. Lancet Microbe . 2021;2:e55. doi: 10.1016/S2666-5247(20)30225-1. [DOI] [PubMed] [Google Scholar]
- 11.Büttner KA, Entrocassi AC, Gallo Vaulet ML, López Aquino D, Caffarena D, et al. ompA sequencing and multilocus sequence typing of lymphogranuloma venereum cases in Buenos Aires reveal new Chlamydia trachomatis genotypes. Microorganisms. 2024;12:587. doi: 10.3390/microorganisms12030587. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Büttner KA, Bregy V, Purushothaman S, Wegner F, Imkamp F, et al. The challenge of sequencing chlamydia trachomatis and other bacterial STI genomes directly from clinical swabs: the optimum solution. Microb Genom. doi: 10.1099/mgen.0.001353. Submitted. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics. 2014;30:2114–2120. doi: 10.1093/bioinformatics/btu170. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Knaus BJ, Grünwald NJ. vcfr: a package to manipulate and visualize variant call format data in R. Mol Ecol Resour. 2017;17:44–53. doi: 10.1111/1755-0998.12549. [DOI] [PubMed] [Google Scholar]
- 15.Hadfield J, Harris SR, Seth-Smith HMB, Parmar S, Andersson P, et al. Comprehensive global genome dynamics of Chlamydia trachomatis show ancient diversification followed by contemporary mixing and recent lineage expansion. Genome Res. 2017;27:1220–1229. doi: 10.1101/gr.212647.116. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Versteeg B, Bruisten SM, Pannekoek Y, Jolley KA, Maiden MCJ, et al. Genomic analyses of the Chlamydia trachomatis core genome show an association between chromosomal genome, plasmid type and disease. BMC Genomics. 2018;19:130. doi: 10.1186/s12864-018-4522-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Minh BQ, Schmidt HA, Chernomor O, Schrempf D, Woodhams MD, et al. IQ-TREE 2: new models and efficient methods for phylogenetic inference in the genomic era. Mol Biol Evol. 2020;37:1530–1534. doi: 10.1093/molbev/msaa015. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Croucher NJ, Page AJ, Connor TR, Delaney AJ, Keane JA, et al. Rapid phylogenetic analysis of large samples of recombinant bacterial whole genome sequences using Gubbins. Nucleic Acids Res. 2015;43:e15. doi: 10.1093/nar/gku1196. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Hadfield J, Croucher NJ, Goater RJ, Abudahab K, Aanensen DM, et al. Phandango: an interactive viewer for bacterial population genomics. Bioinformatics. 2017;34:292–293. doi: 10.1101/119545. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Larsson A. AliView: a fast and lightweight alignment viewer and editor for large datasets. Bioinformatics. 2014;30:3276–3278. doi: 10.1093/bioinformatics/btu531. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Peuchant O, Laurier-Nadalié C, Albucher L, Balcon C, Dolzy A, et al. Anorectal lymphogranuloma venereum among men who have sex with men: a 3-year nationwide survey, France, 2020 to 2022. Euro Surveill. 2024;29:2300520. doi: 10.2807/1560-7917.ES.2024.29.19.2300520. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Jeffrey BM, Suchland RJ, Quinn KL, Davidson JR, Stamm WE, et al. Genome sequencing of recent clinical Chlamydia trachomatis strains identifies loci associated with tissue tropism and regions of apparent recombination. Infect Immun. 2010;78:2544–2553. doi: 10.1128/IAI.01324-09. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Bowden KE, Joseph SJ, Cartee JC, Ziklo N, Danavall D, et al. Whole-genome enrichment and sequencing of Chlamydia trachomatis directly from patient clinical vaginal and rectal swabs. mSphere. 2021;6:e01302-20. doi: 10.1128/mSphere.01302-20. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Hamill M, Benn P, Carder C, Copas A, Ward H, et al. The clinical manifestations of anorectal infection with lymphogranuloma venereum (LGV) versus non-LGV strains of Chlamydia trachomatis: a case-control study in homosexual men. Int J STD AIDS. 2007;18:472–475. doi: 10.1258/095646207781147319. [DOI] [PubMed] [Google Scholar]
- 25.Rodriguez-Dominguez M, Gonzalez-Alba JM, Puerta T, Menendez B, Sanchez-Diaz AM, et al. High prevalence of co-infections by invasive and non-invasive Chlamydia trachomatis genotypes during the lymphogranuloma venereum outbreak in Spain. PLoS One. 2015;10:e0126145. doi: 10.1371/journal.pone.0126145. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Somboonna N, Wan R, Ojcius DM, Pettengill MA, Joseph SJ, et al. Hypervirulent Chlamydia trachomatis clinical strain is a recombinant between lymphogranuloma venereum (L2) and D lineages. mBio. 2011;2:e00045–11. doi: 10.1128/mBio.00045-11. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Citations
- Andrea Büttner K, Wegner F, Vera B, Entrocassi AC, Gallo Vaulet ML, et al. 2025. Chlamydia trachomatis genomes from rectal samples: description of new clade comprising ompA-genotype L4 from Argentina. Figshare. Dataset . [DOI] [PMC free article] [PubMed]