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Chlamydia trachomatis Pathogenicity and Disease
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Chlamydia trachomatis Pathogenicity and Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 15423

Special Issue Editor

Dr. Rosa Sessa

E-Mail Website
Guest Editor
Department of Public Health and Infectious Diseases, “Sapienza” University, 00185 Rome, Italy
Interests: identification of host defence factors towards C. trachomatis genital infection; study of C. trachomatis role in the pathogenesis of male infertility; study of chlamydia-host cell interaction; identification of new anti-chlamydial drugs; study of the etiopathogenic role Chlamydia pneumoniae in the chronic inflammatory diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Chlamydia trachomatis, responsible for genital infection, trachoma, and lymphogranuloma venereum according to the specific serotype, is still a relevant public health problem worldwide due to the high prevalence of asymptomatic infections in both women and men, favoring the onset of chronic complications, such as pelvic inflammatory disease and ectopic pregnancy for women, epididymitis and proctitis for men, as well as reactive arthritis and infertility for both sexes. These are likely due to the long-term persistence of C. trachomatis infection in the host organism, leading to a chronic inflammatory state and the consequent tissue damage.

To date, many critical questions on the pathogenesis of C. trachomatis infection remain to be answered. For example, the nature of the host innate immune response to C. trachomatis, as well as the virulence factors involved, is a key issue that needs further investigation to clarify the molecular and cellular mechanisms responsible for tissue damage associated to chlamydial infection.

In order to shed light on the etiopathogenesis and host cell response mechanisms of damaging C. trachomatis infection, this Special Issue is dedicated to current progress in chlamydial infection pathogenesis and related diseases.

Prof. Dr. Rosa Sessa
Guest Editor

Manuscript Submission Information

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Keywords

  • Chlamydia trachomatis
  • virulence factors
  • host susceptibility or resistance
  • innate and adaptive
  • immune responses
  • genetic studies
  • cervico-vaginal microbiota
  • clinical outcomes with molecular study

Published Papers (7 papers)

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Editorial

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2 pages, 194 KiB  
Editorial
Towards a Deeper Understanding of Chlamydia trachomatis Pathogenetic Mechanisms: Editorial to the Special Issue “Chlamydia trachomatis Pathogenicity and Disease”
by Simone Filardo, Marisa Di Pietro and Rosa Sessa
Int. J. Mol. Sci. 2022, 23(7), 3943; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23073943 - 01 Apr 2022
Viewed by 2820
Abstract
Chlamydia trachomatis, an obligate intracellular Gram-negative bacterium, is characterized by a wide range of different serotypes responsible for several local or systemic human diseases, including genital tract manifestations (D–K), trachoma (A–C), and lymphogranuloma venereum (L1–3) [...] Full article
(This article belongs to the Special Issue Chlamydia trachomatis Pathogenicity and Disease)

Research

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11 pages, 921 KiB  
Article
Genetic Variation in the MBL2 Gene Is Associated with Chlamydia trachomatis Infection and Host Humoral Response to Chlamydia trachomatis Infection
by Stephan P. Verweij, Remco P. H. Peters, Arnold Catsburg, Henry J. C. de Vries, Sander Ouburg and Servaas A. Morré
Int. J. Mol. Sci. 2022, 23(16), 9292; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23169292 - 18 Aug 2022
Cited by 1 | Viewed by 1391
Abstract
This study aims to assess the potential association of MBL2 gene single nucleotide polymorphisms (SNPs) to Chlamydia trachomatis infection. We analysed a selected sample of 492 DNA and serum specimens from Dutch Caucasian women. Women were categorized into four groups of infection status [...] Read more.
This study aims to assess the potential association of MBL2 gene single nucleotide polymorphisms (SNPs) to Chlamydia trachomatis infection. We analysed a selected sample of 492 DNA and serum specimens from Dutch Caucasian women. Women were categorized into four groups of infection status based on the results of DNA and antibody tests for C. trachomatis: Ct-DNA+/IgG+, Ct-DNA+/IgG−, Ct-DNA−/IgG+, and Ct-DNA−/IgG−. We compared six MBL2 SNPs (−619G > C (H/L), −290G > C (Y/X), −66C > T (P/Q), +154C > T (A/D), +161A > G (A/B), and +170A > G (A/C)) and their respective haplotypes in relation to these different subgroups. The −619C (L) allele was less present within the Ct-DNA−/IgG+ group compared with the Ct-DNA−/IgG− group (OR = 0.49; 95% CI: 0.28–0.83), while the +170G (C) allele was observed more in the Ct-DNA+/IgG+ group as compared with the Ct-DNA−/IgG− group (OR = 2.4; 95% CI: 1.1–5.4). The HYA/HYA haplotype was more often present in the Ct-DNA−/IgG− group compared with the Ct-DNA+/IgG+ group (OR = 0.37; 95% CI: 0.16–0.87). The +170G (C) allele was associated with increased IgG production (p = 0.048) in C. trachomatis PCR-positive women. This study shows associations for MBL in immune reactions to C. trachomatis. We showed clear associations between MBL2 genotypes, haplotypes, and individuals’ stages of C. trachomatis DNA and IgG positivity. Full article
(This article belongs to the Special Issue Chlamydia trachomatis Pathogenicity and Disease)
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14 pages, 3193 KiB  
Article
Bortezomib Eliminates Persistent Chlamydia trachomatis Infection through Rapid and Specific Host Cell Apoptosis
by Ryota Itoh, Yusuke Kurihara, Michinobu Yoshimura and Kenji Hiromatsu
Int. J. Mol. Sci. 2022, 23(13), 7434; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23137434 - 04 Jul 2022
Cited by 2 | Viewed by 2222
Abstract
Chlamydia trachomatis, a parasitic intracellular bacterium, is a major human pathogen that causes millions of trachoma, sexually transmitted infections, and pneumonia cases worldwide. Previously, peptidomimetic inhibitors consisting of a hydrophobic dipeptide derivative exhibited significant inhibitory effects against chlamydial growth. Based on this [...] Read more.
Chlamydia trachomatis, a parasitic intracellular bacterium, is a major human pathogen that causes millions of trachoma, sexually transmitted infections, and pneumonia cases worldwide. Previously, peptidomimetic inhibitors consisting of a hydrophobic dipeptide derivative exhibited significant inhibitory effects against chlamydial growth. Based on this finding, this study showed that both bortezomib (BTZ) and ixazomib (IXA), anticancer drugs characterized by proteasome inhibitors, have intensive inhibitory activity against Chlamydia. Both BTZ and IXA consisted of hydrophobic dipeptide derivatives and strongly restricted the growth of Chlamydia (BTZ, IC50 = 24 nM). In contrast, no growth inhibitory effect was observed for other nonintracellular parasitic bacteria, such as Escherichia coli. BTZ and IXA appeared to inhibit chlamydial growth bacteriostatically via electron microscopy. Surprisingly, Chlamydia-infected cells that induced a persistent infection state were selectively eliminated by BTZ treatment, whereas uninfected cells survived. These results strongly suggested the potential of boron compounds based on hydrophobic dipeptides for treating chlamydial infections, including persistent infections, which may be useful for future therapeutic use in chlamydial infectious diseases. Full article
(This article belongs to the Special Issue Chlamydia trachomatis Pathogenicity and Disease)
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16 pages, 2569 KiB  
Article
Modified Fluoroquinolones as Antimicrobial Compounds Targeting Chlamydia trachomatis
by Thi Huyen Vu, Erika Adhel, Katarina Vielfort, Ngûyet-Thanh Ha Duong, Guillaume Anquetin, Katy Jeannot, Philippe Verbeke, Sofia Hjalmar, Åsa Gylfe and Nawal Serradji
Int. J. Mol. Sci. 2022, 23(12), 6741; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23126741 - 16 Jun 2022
Cited by 2 | Viewed by 2006
Abstract
Chlamydia trachomatis causes the most common sexually transmitted bacterial infection and trachoma, an eye infection. Untreated infections can lead to sequelae, such as infertility and ectopic pregnancy in women and blindness. We previously enhanced the antichlamydial activity of the fluoroquinolone ciprofloxacin by grafting [...] Read more.
Chlamydia trachomatis causes the most common sexually transmitted bacterial infection and trachoma, an eye infection. Untreated infections can lead to sequelae, such as infertility and ectopic pregnancy in women and blindness. We previously enhanced the antichlamydial activity of the fluoroquinolone ciprofloxacin by grafting a metal chelating moiety onto it. In the present study, we pursued this pharmacomodulation and obtained nanomolar active molecules (EC50) against this pathogen. This gain in activity prompted us to evaluate the antibacterial activity of this family of molecules against other pathogenic bacteria, such as Neisseria gonorrhoeae and bacteria from the ESKAPE group. The results show that the novel molecules have selectively improved activity against C. trachomatis and demonstrate how the antichlamydial effect of fluoroquinolones can be enhanced. Full article
(This article belongs to the Special Issue Chlamydia trachomatis Pathogenicity and Disease)
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28 pages, 5437 KiB  
Article
Transactive Response DNA-Binding Protein (TARDBP/TDP-43) Regulates Cell Permissivity to HIV-1 Infection by Acting on HDAC6
by Romina Cabrera-Rodríguez, Silvia Pérez-Yanes, Rafaela Montelongo, José M. Lorenzo-Salazar, Judith Estévez-Herrera, Jonay García-Luis, Antonio Íñigo-Campos, Luis A. Rubio-Rodríguez, Adrián Muñoz-Barrera, Rodrigo Trujillo-González, Roberto Dorta-Guerra, Concha Casado, María Pernas, Julià Blanco, Carlos Flores and Agustín Valenzuela-Fernández
Int. J. Mol. Sci. 2022, 23(11), 6180; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23116180 - 31 May 2022
Cited by 7 | Viewed by 2315
Abstract
The transactive response DNA-binding protein (TARDBP/TDP-43) influences the processing of diverse transcripts, including that of histone deacetylase 6 (HDAC6). Here, we assessed TDP-43 activity in terms of regulating CD4+ T-cell permissivity to HIV-1 infection. We observed that overexpression of wt-TDP-43 increased both mRNA [...] Read more.
The transactive response DNA-binding protein (TARDBP/TDP-43) influences the processing of diverse transcripts, including that of histone deacetylase 6 (HDAC6). Here, we assessed TDP-43 activity in terms of regulating CD4+ T-cell permissivity to HIV-1 infection. We observed that overexpression of wt-TDP-43 increased both mRNA and protein levels of HDAC6, resulting in impaired HIV-1 infection independently of the viral envelope glycoprotein complex (Env) tropism. Consistently, using an HIV-1 Env-mediated cell-to-cell fusion model, the overexpression of TDP-43 levels negatively affected viral Env fusion capacity. Silencing of endogenous TDP-43 significantly decreased HDAC6 levels and increased the fusogenic and infection activities of the HIV-1 Env. Using pseudovirus bearing primary viral Envs from HIV-1 individuals, overexpression of wt-TDP-43 strongly reduced the infection activity of Envs from viremic non-progressors (VNP) and rapid progressors (RP) patients down to the levels of the inefficient HIV-1 Envs observed in long-term non-progressor elite controllers (LTNP-EC). On the contrary, silencing endogenous TDP-43 significantly favored the infectivity of primary Envs from VNP and RP individuals, and notably increased the infection of those from LTNP-EC. Taken together, our results indicate that TDP-43 shapes cell permissivity to HIV-1 infection, affecting viral Env fusion and infection capacities by altering the HDAC6 levels and associated tubulin-deacetylase anti-HIV-1 activity. Full article
(This article belongs to the Special Issue Chlamydia trachomatis Pathogenicity and Disease)
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13 pages, 1465 KiB  
Article
First-Void Urine Microbiome in Women with Chlamydia trachomatis Infection
by Valeria Gaspari, Camilla Ceccarani, Marco Severgnini, Gionathan Orioni, Tania Camboni, Luca Laghi, Sara Morselli, Claudio Foschi, Antonella Marangoni, Clarissa Consolandi and Bianca Maria Piraccini
Int. J. Mol. Sci. 2022, 23(10), 5625; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23105625 - 17 May 2022
Cited by 1 | Viewed by 1529
Abstract
Background: Chlamydia trachomatis (CT) is the agent of the most common bacterial sexually transmitted infection worldwide. Until now, little information is available about the microbial composition of urine samples during CT urethritis. Therefore, in this study, we characterized the microbiome and metabolome profiles [...] Read more.
Background: Chlamydia trachomatis (CT) is the agent of the most common bacterial sexually transmitted infection worldwide. Until now, little information is available about the microbial composition of urine samples during CT urethritis. Therefore, in this study, we characterized the microbiome and metabolome profiles of first-void urines in a cohort of women with CT urethral infection attending an STI clinic. Methods: Based on CT positivity by nucleic acid amplification techniques on urine samples, the enrolled women were divided into two groups, i.e., “CT-negative” (n = 21) and “CT-positive” (n = 11). Urine samples were employed for (i) the microbiome profile analysis by means of 16s rRNA gene sequencing and (ii) the metabolome analysis by 1H-NMR. Results: Irrespective of CT infection, the microbiome of first-void urines was mainly dominated by Lactobacillus, L. iners and L. crispatus being the most represented species. CT-positive samples were characterized by reduced microbial biodiversity compared to the controls. Moreover, a significant reduction of the Mycoplasmataceae family—in particular, of the Ureaplasma parvum species—was observed during CT infection. The Chlamydia genus was positively correlated with urine hippurate and lactulose. Conclusions: These data can help elucidate the pathogenesis of chlamydial urogenital infections, as well as to set up innovative diagnostic and therapeutic approaches. Full article
(This article belongs to the Special Issue Chlamydia trachomatis Pathogenicity and Disease)
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Review

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14 pages, 1239 KiB  
Review
Cervicovaginal Microbiota Composition in Chlamydia trachomatis Infection: A Systematic Review and Meta-Analysis
by Marisa Di Pietro, Simone Filardo, Ilaria Simonelli, Patrizio Pasqualetti and Rosa Sessa
Int. J. Mol. Sci. 2022, 23(17), 9554; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23179554 - 23 Aug 2022
Cited by 4 | Viewed by 1733
Abstract
In healthy women, the cervicovaginal microbiota is characterized by the predominance of Lactobacillus spp., whereas the overgrowth of anaerobic bacteria leads to dysbiosis, known to increase the risk of acquiring genital infections like Chlamydia trachomatis. In the last decade, a growing body [...] Read more.
In healthy women, the cervicovaginal microbiota is characterized by the predominance of Lactobacillus spp., whereas the overgrowth of anaerobic bacteria leads to dysbiosis, known to increase the risk of acquiring genital infections like Chlamydia trachomatis. In the last decade, a growing body of research has investigated the composition of the cervicovaginal microbiota associated with chlamydial infection via 16s rDNA sequencing, with contrasting results. A systematic review and a meta-analysis, performed on the alpha-diversity indices, were conducted to summarize the scientific evidence on the cervicovaginal microbiota composition in C. trachomatis infection. Databases PubMed, Scopus and Web of Science were searched with the following strategy: “Chlamydia trachomatis” AND “micro*”. The diversity indices considered for the meta-analysis were Operational Taxonomic Unit (OTU) number, Chao1, phylogenetic diversity whole tree, Shannon’s, Pielou’s and Simpson’s diversity indexes. The search yielded 425 abstracts for initial review, of which 16 met the inclusion criteria. The results suggested that the cervicovaginal microbiota in C. trachomatis-positive women was characterized by Lactobacillus iners dominance, or by a diverse mix of facultative or strict anaerobes. The meta-analysis, instead, did not show any difference in the microbial biodiversity between Chlamydia-positive and healthy women. Additional research is clearly required to deepen our knowledge on the interplay between the resident microflora and C. trachomatis in the genital microenvironment. Full article
(This article belongs to the Special Issue Chlamydia trachomatis Pathogenicity and Disease)
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