Chlamydiae and Chlamydia like Bacteria

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Medical Microbiology".

Deadline for manuscript submissions: closed (30 November 2019) | Viewed by 74793

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Guest Editor
1. Laboratory of Immunogenetics, Department of Medical Microbiology and Infection Control, VU University Medical Center / Amsterdam UMC, Amsterdam, The Netherlands
2. Director of the Institute for Public Health Genomics (IPHG), Department of Genetics and Cell Biology, Research Institute GROW, Maastricht, The Netherlands
Interests: chlamydia trachomatis; neisseria gonorrhoeae; trichomonas vaginalis; mycoplasma genitalium
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Guest Editor
Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Medical Microbiology & Infection Control, Laboratory of Immunogenetics, Amsterdam, The Netherlands
Interests: chlamydia trachomatis infections
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are proud to announce that the journal Microorganisms (https://www.mdpi.com/journal/microorganisms) will be the sponsor for the best Oral Presentation at the 13th Annual Amsterdam Chlamydia Meeting (13th AACM) held 1 February 2019 in Amsterdam (see more details at www.AACM.nl). In addition, linked to the 13th AACM, a Special Issue of Microorganisms will be launched called “Chlamydiae and Chlamydia-like Bacteria”, and presenters at the 13th AACM can submit a manuscript in the month following the AACM (before 1 April 2019) with a publication goal of the Special Issue being before summer 2019. Microorganisms is PubMed retrievable, and will receive an impact factor in July 2019 (based on the journal’s citations in the last two years, it will be approximately 2.5). Please consider publishing your work presented at AACM in this Special Issue. Further updates will follow in the upcoming months.

Besides papers from 13th AACM, this Special Issue also welcomes any submission from Chlamydia field to provide a wide overview on Chlamydiae and Chlamydia-like Bacteria research.

Manuscript submissions open: 1 October 2018

Prof. Dr. Servaas A. Morré
Dr. Sander Ouburg
Guest Editors

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Published Papers (20 papers)

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9 pages, 248 KiB  
Article
Screening of Chlamydia trachomatis and Waddlia chondrophila Antibodies in Women with Tubal Factor Infertility
by Wies T.M. van Dooremalen, Stephan P. Verweij, Janneke E. den Hartog, Carole Kebbi-Beghdadi, Sander Ouburg, Gilbert Greub, Servaas A. Morré and Anne Ammerdorffer
Microorganisms 2020, 8(6), 918; https://doi.org/10.3390/microorganisms8060918 - 17 Jun 2020
Cited by 4 | Viewed by 2276
Abstract
Waddlia chondrophila is an emerging intracellular pathogen belonging to the order of Chlamydiales, and was previously associated with adverse pregnancy outcomes, as well as tubal factor infertility (TFI). In this study, we investigate the link between both W. chondrophila and Chlamydia trachomatis [...] Read more.
Waddlia chondrophila is an emerging intracellular pathogen belonging to the order of Chlamydiales, and was previously associated with adverse pregnancy outcomes, as well as tubal factor infertility (TFI). In this study, we investigate the link between both W. chondrophila and Chlamydia trachomatis IgG seropositivity and TFI. Antibodies against both bacteria were measured in 890 serum samples of women visiting a fertility clinic. After a hysterosalpingography and/or laparoscopy, they were classified as either TFI-negative (TFI−) or TFI-positive (TFI+). The total seroprevalence was 13.4% for C. trachomatis and 38.8% for W. chondrophila. C. trachomatis antibodies were present significantly more often in the TFI+ group than in the TFI− group, while for W. chondrophila no difference could be observed. In conclusion, our study confirms the association between C. trachomatis seropositivity and TFI, but no association was found between W. chondrophila seropositivity and TFI. The high percentage of W. chondrophila seropositivity in all women attending a fertility clinic does, however, demonstrate the need for further research on this Chlamydia-like bacterium and its possible role in infertility. Full article
(This article belongs to the Special Issue Chlamydiae and Chlamydia like Bacteria)
19 pages, 2435 KiB  
Article
Eukaryotic Cell Permeabilisation to Identify New Putative Chlamydial Type III Secretion System Effectors Secreted within Host Cell Cytoplasm
by Carole Kebbi-Beghdadi, Ludovic Pilloux, Virginie Martin and Gilbert Greub
Microorganisms 2020, 8(3), 361; https://doi.org/10.3390/microorganisms8030361 - 03 Mar 2020
Cited by 3 | Viewed by 3220
Abstract
Chlamydia trachomatis and Waddlia chondrophila are strict intracellular bacteria belonging to the Chlamydiales order. C. trachomatis is the most frequent bacterial cause of genital and ocular infections whereas W. chondrophila is an opportunistic pathogen associated with adverse pregnancy outcomes and respiratory infections. [...] Read more.
Chlamydia trachomatis and Waddlia chondrophila are strict intracellular bacteria belonging to the Chlamydiales order. C. trachomatis is the most frequent bacterial cause of genital and ocular infections whereas W. chondrophila is an opportunistic pathogen associated with adverse pregnancy outcomes and respiratory infections. Being strictly intracellular, these bacteria are engaged in a complex interplay with their hosts to modulate their environment and create optimal conditions for completing their life cycle. For this purpose, they possess several secretion pathways and, in particular, a Type III Secretion System (T3SS) devoted to the delivery of effector proteins in the host cell cytosol. Identifying these effectors is a crucial step in understanding the molecular basis of bacterial pathogenesis. Following incubation of infected cells with perfringolysin O, a pore-forming toxin that binds cholesterol present in plasma membranes, we analysed by mass spectrometry the protein content of the host cell cytoplasm. We identified 13 putative effectors secreted by C. trachomatis and 19 secreted by W. chondrophila. Using Y. enterocolitica as a heterologous expression and secretion system, we confirmed that four of these identified proteins are secreted by the T3SS. Two W. chondrophila T3SS effectors (hypothetical proteins Wcw_0499 and Wcw_1706) were further characterised and demonstrated to be early/mid-cycle effectors. In addition, Wcw_1706 is associated with a tetratricopeptide domain-containing protein homologous to C. trachomatis class II chaperone. Furthermore, we identified a novel C. trachomatis effector, CT460 that localises in the eukaryotic nucleus when ectopically expressed in 293 T cells. Full article
(This article belongs to the Special Issue Chlamydiae and Chlamydia like Bacteria)
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13 pages, 2421 KiB  
Article
Interferon-γ Possesses Anti-Microbial and Immunomodulatory Activity on a Chlamydia trachomatis Infection Model of Primary Human Synovial Fibroblasts
by Marisa Di Pietro, Simone Filardo, Federica Frasca, Carolina Scagnolari, Martina Manera, Vincenzo Sessa, Guido Antonelli and Rosa Sessa
Microorganisms 2020, 8(2), 235; https://doi.org/10.3390/microorganisms8020235 - 10 Feb 2020
Cited by 6 | Viewed by 2298
Abstract
Chlamydia trachomatis, an obligate intracellular pathogen, is the most common cause of bacterial sexually transmitted diseases, and it is potentially responsible for severe chronic sequelae, such as reactive arthritis. To date, details of the mechanisms by which Chlamydiae induce innate antimicrobial pathways [...] Read more.
Chlamydia trachomatis, an obligate intracellular pathogen, is the most common cause of bacterial sexually transmitted diseases, and it is potentially responsible for severe chronic sequelae, such as reactive arthritis. To date, details of the mechanisms by which Chlamydiae induce innate antimicrobial pathways in synovial fibroblasts, are not well characterized; therefore, herein, we investigated the effects of interferon (IFN)α, IFNβ, and IFNγ on the infection, and replication phases of the C. trachomatis developmental cycle, as well as on the induction of pattern recognition receptors (PRRs) and IFN-related pathways. To do so, we set up an in vitro chlamydial-infection model of primary human synovial cells treated with IFNs before or after the infection. We then determined the number of chlamydial inclusion forming units and inclusion size, as well as the expression of toll like receptor (TLR)2, TLR3, TLR4, cyclic GMP-AMP synthase (cGAS), stimulator of IFN gene (STING), IRF9, ISG56, and GBP1. The main result of our study is the significant inhibition of C. trachomatis infection and replication in human synovial cells following the treatment with IFNγ, whereas IFN-I proved to be ineffective. Furthermore, IFNγ greatly upregulated all the PRRs and ISGs examined. In conclusion, IFNγ exhibited a potent anti-Chlamydia activity in human synovial cells as well as the ability to induce a strong increase of innate immune pathways. Full article
(This article belongs to the Special Issue Chlamydiae and Chlamydia like Bacteria)
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8 pages, 263 KiB  
Article
Waddlia chondrophila and Male Infertility
by David Baud, Nicolas Vulliemoz, Maria Verónica Morales Zapata, Gilbert Greub, Manon Vouga and Milos Stojanov
Microorganisms 2020, 8(1), 136; https://doi.org/10.3390/microorganisms8010136 - 17 Jan 2020
Cited by 6 | Viewed by 2681
Abstract
Waddlia chondrophila, a Chlamydia-like bacterium, has been previously associated with adverse pregnancy outcomes. Analogously to Chlamydia trachomatis, W. chondrophila also negatively impacts human semen and may be a source of impaired male fertility. In this study, we analyzed W. chondrophila [...] Read more.
Waddlia chondrophila, a Chlamydia-like bacterium, has been previously associated with adverse pregnancy outcomes. Analogously to Chlamydia trachomatis, W. chondrophila also negatively impacts human semen and may be a source of impaired male fertility. In this study, we analyzed W. chondrophila seroprevalence in a population of male patients of infertile couples and the impact of past exposition to this bacterium on semen parameters. Our results show a surprisingly high seroprevalence of W. chondrophila, which contrasts with a previous study focusing on a population of healthy men. Nevertheless, we did not observe any significant association between positive serology and abnormal sperm parameters. This may suggest that a negative impact on semen is observed only during an ongoing infection. Alternatively, W. chondrophila may have an immune impact on male fertility, as previously postulated for women with adverse pregnancy outcomes. Full article
(This article belongs to the Special Issue Chlamydiae and Chlamydia like Bacteria)
20 pages, 2922 KiB  
Article
Diverse Stress-Inducing Treatments cause Distinct Aberrant Body Morphologies in the Chlamydia-Related Bacterium, Waddlia chondrophila
by Aurélie Scherler, Nicolas Jacquier, Carole Kebbi-Beghdadi and Gilbert Greub
Microorganisms 2020, 8(1), 89; https://doi.org/10.3390/microorganisms8010089 - 09 Jan 2020
Cited by 9 | Viewed by 4218
Abstract
Chlamydiae, such as Chlamydia trachomatis and Chlamydia pneumoniae, can cause chronic infections. It is believed that persistent forms called aberrant bodies (ABs) might be involved in this process. AB formation seems to be a common trait of all members of the Chlamydiales [...] Read more.
Chlamydiae, such as Chlamydia trachomatis and Chlamydia pneumoniae, can cause chronic infections. It is believed that persistent forms called aberrant bodies (ABs) might be involved in this process. AB formation seems to be a common trait of all members of the Chlamydiales order and is caused by distinct stress stimuli, such as β-lactam antibiotics or nutrient starvation. While the diverse stimuli inducing ABs are well described, no comprehensive morphological characterization has been performed in Chlamydiales up to now. We thus infected mammalian cells with the Chlamydia-related bacterium Waddlia chondrophila and induced AB formation using different stimuli. Their morphology, differences in DNA content and in gene expression were assessed by immunofluorescence, quantitative PCR, and reverse transcription PCR, respectively. All stimuli induced AB formation. Interestingly, we show here for the first time that the DNA gyrase inhibitor novobiocin also caused appearance of ABs. Two distinct patterns of ABs could be defined, according to their morphology and number: (i) small and multiple ABs versus (ii) large and rare ABs. DNA replication of W. chondrophila was generally not affected by the different treatments. Finally, no correlation could be observed between specific types of ABs and expression patterns of mreB and rodZ genes. Full article
(This article belongs to the Special Issue Chlamydiae and Chlamydia like Bacteria)
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18 pages, 1812 KiB  
Article
Chlamydia trachomatis Whole-Proteome Microarray Analysis of The Netherlands Chlamydia Cohort Study
by Katrin Hufnagel, Bernice Hoenderboom, Christoph Harmel, Juliane K. Rohland, Birgit H.B. van Benthem, Servaas A. Morré and Tim Waterboer
Microorganisms 2019, 7(12), 703; https://doi.org/10.3390/microorganisms7120703 - 16 Dec 2019
Cited by 8 | Viewed by 2710
Abstract
Chlamydia trachomatis (Ct) whole-proteome microarrays were utilized to identify antibody patterns associated with infection; pelvic inflammatory disease (PID), tubal factor infertility, chronic pelvic pain (CPP) and ectopic pregnancy in a subsample of the Netherlands Chlamydia cohort study. Serum pools were analyzed on whole-proteome [...] Read more.
Chlamydia trachomatis (Ct) whole-proteome microarrays were utilized to identify antibody patterns associated with infection; pelvic inflammatory disease (PID), tubal factor infertility, chronic pelvic pain (CPP) and ectopic pregnancy in a subsample of the Netherlands Chlamydia cohort study. Serum pools were analyzed on whole-proteome arrays. The 121 most reactive antigens identified during whole-proteome arrays were selected for further analysis with minimized microarrays that allowed for single sera analysis. From the 232 single sera; 145 (62.5%) serum samples were reactive for at least one antigen. To discriminate between positive and negative serum samples; we created a panel of in total 18 antigens which identified 96% of all microarray positive samples. Antigens CT_858; CT_813 and CT_142 were most reactive. Comparison of antibody reactivity’s among women with and without Ct related sequelae revealed that the reactivity of CT_813 and CT_142 was less common among women with PID compared to women without (29.0% versus 58.6%, p = 0.005 and 25.8% versus 50.6%, p = 0.017 respectively). CT_858 was less common among CPP cases compared to controls (33.3% versus 58.6; p = 0.028). Using a whole-proteome array to select antigens for minimized arrays allows for the identification of novel informative antigens as general infection markers or disease associated antigens Full article
(This article belongs to the Special Issue Chlamydiae and Chlamydia like Bacteria)
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17 pages, 2688 KiB  
Article
Interactions Screenings Unearth Potential New Divisome Components in the Chlamydia-Related Bacterium, Waddlia chondrophila
by Firuza Bayramova, Nicolas Jacquier and Gilbert Greub
Microorganisms 2019, 7(12), 617; https://doi.org/10.3390/microorganisms7120617 - 26 Nov 2019
Cited by 3 | Viewed by 2640
Abstract
Chlamydiales order members are obligate intracellular bacteria, dividing by binary fission. However, Chlamydiales lack the otherwise conserved homologue of the bacterial division organizer FtsZ and certain division protein homologues. FtsZ might be functionally replaced in Chlamydiales by the actin homologue MreB. RodZ, the [...] Read more.
Chlamydiales order members are obligate intracellular bacteria, dividing by binary fission. However, Chlamydiales lack the otherwise conserved homologue of the bacterial division organizer FtsZ and certain division protein homologues. FtsZ might be functionally replaced in Chlamydiales by the actin homologue MreB. RodZ, the membrane anchor of MreB, localizes early at the division septum. In order to better characterize the organization of the chlamydial divisome, we performed co-immunoprecipitations and yeast-two hybrid assays to study the interactome of RodZ, using Waddlia chondrophila, a potentially pathogenic Chlamydia-related bacterium, as a model organism. Three potential interactors were further investigated: SecA, FtsH, and SufD. The gene and protein expression profiles of these three genes were measured and are comparable with recently described division proteins. Moreover, SecA, FtsH, and SufD all showed a peripheral localization, consistent with putative inner membrane localization and interaction with RodZ. Notably, heterologous overexpression of the abovementioned proteins could not complement E. coli mutants, indicating that these proteins might play different functions in these two bacteria or that important regulators are not conserved. Altogether, this study brings new insights to the composition of the chlamydial divisome and points to links between protein secretion, degradation, iron homeostasis, and chlamydial division. Full article
(This article belongs to the Special Issue Chlamydiae and Chlamydia like Bacteria)
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12 pages, 259 KiB  
Article
Sexually Transmitted Infections and Behavioral Determinants of Sexual and Reproductive Health in the Allahabad District (India) Based on Data from the ChlamIndia Study
by Pierre P. M. Thomas, Jay Yadav, Rajiv Kant, Elena Ambrosino, Smita Srivastava, Gurpreet Batra, Arvind Dayal, Nidhi Masih, Akash Pandey, Saurav Saha, Roel Heijmans, Jonathan A. Lal and Servaas A. Morré
Microorganisms 2019, 7(11), 557; https://doi.org/10.3390/microorganisms7110557 - 12 Nov 2019
Cited by 4 | Viewed by 3487
Abstract
Background: Sexually transmitted infections (STIs), like Chlamydia trachomatis and Neisseria gonorrhoeae (CT and NG, respectively) are linked to an important sexual and reproductive health (SRH) burden worldwide. Behavior is an important predictor for SRH, as it dictates the risk for STIs. Assessing the [...] Read more.
Background: Sexually transmitted infections (STIs), like Chlamydia trachomatis and Neisseria gonorrhoeae (CT and NG, respectively) are linked to an important sexual and reproductive health (SRH) burden worldwide. Behavior is an important predictor for SRH, as it dictates the risk for STIs. Assessing the behavior of a population helps to assess its risk profile. Methods: Study participants were recruited at a gynecology outpatient department (OPD) in the Allahabad district in Uttar Pradesh India, and a questionnaire was used to assess demographics, SRH, and obstetric history. Patients provided three samples (urine, vaginal swab, and whole blood). These samples were used to identify CT and NG using PCR/NAAT and CT IgG ELISA. Results: A total of 296 women were included for testing; mean age was 29 years. No positive cases of CT and NG were observed using PCR/NAAT. A 7% (22/296) positivity rate for CT was observed using IgG ELISA. No positive association was found between serology and symptoms (vaginal discharge, abdominal pain, dysuria, and dyspareunia) or adverse pregnancy outcomes (miscarriage and stillbirth). Positive relations with CT could be observed with consumption of alcohol, illiteracy, and tenesmus (p-value 0.02–0.03). Discussion: STI prevalence in this study was low, but a high burden of SRH morbidity was observed, with a high symptomatic load. High rates of miscarriage (31%) and stillbirth (8%) were also observed among study subjects. No associations could be found between these ailments and CT infection. These rates are high even for low- and middle-income country standards. Conclusion: This study puts forward high rates of SRH morbidity, and instances of adverse reproductive health outcomes are highlighted in this study, although no associations with CT infection could be found. This warrants more investigation into the causes leading to these complaints in the Indian scenario and potential biases to NAAT testing, such as consumption of over-the-counter antimicrobials. Full article
(This article belongs to the Special Issue Chlamydiae and Chlamydia like Bacteria)
14 pages, 487 KiB  
Article
Antibody Testing in Estimating Past Exposure to Chlamydia trachomatis in The Netherlands Chlamydia Cohort Study
by Bernice M. Hoenderboom, Michelle E. van Willige, Jolande A. Land, Jolein Pleijster, Hannelore M. Götz, Jan E. A. M. van Bergen, Nicole H. T. M. Dukers-Muijrers, Christian J. P. A. Hoebe, Birgit H. B. van Benthem and Servaas A. Morré
Microorganisms 2019, 7(10), 442; https://doi.org/10.3390/microorganisms7100442 - 11 Oct 2019
Cited by 4 | Viewed by 3601
Abstract
The asymptomatic course of Chlamydia trachomatis (CT) infections can result in underestimated CT lifetime prevalence. Antibody testing might improve this estimate. We assessed CT antibody positivity and predictive factors thereof in the Netherlands Chlamydia Cohort Study. Women who had ≥1 CT Nucleic Acid [...] Read more.
The asymptomatic course of Chlamydia trachomatis (CT) infections can result in underestimated CT lifetime prevalence. Antibody testing might improve this estimate. We assessed CT antibody positivity and predictive factors thereof in the Netherlands Chlamydia Cohort Study. Women who had ≥1 CT Nucleic Acid Amplification Test (NAAT) in the study (2008–2011) and who provided self-reported information on NAATs were tested for CT major outer membrane protein specific IgG in serum (2016). CT antibody positivity was assessed and predictive factors were identified using multivariable logistic regressions, separately for CT-positive women (≥1 positive NAAT or ≥1 self-reported positive CT test) and CT-negative women (negative by study NAAT and self-report). Of the 3,613 women studied, 833 (23.1%) were CT -positive. Among the CT-negative women, 208 (7.5%, 95% CI 6.5–8.5) tested positive for CT antibodies. This increased CT lifetime prevalence with 5.8% (95% CI 5.0–6.5). Among women with a CT-positive history, 338 (40.6%, 95% CI 38.5–44.1) tested positive. Predictive factors for antibody positivity related to lower social economic status, sexual risk behavior, multiple infections, higher body mass index, and non-smoking. CT antibody testing significantly increased the lifetime prevalence. Combining NAAT outcomes, self-reported positive tests, and antibody testing reduced misclassification in CT prevalence estimates. Full article
(This article belongs to the Special Issue Chlamydiae and Chlamydia like Bacteria)
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10 pages, 653 KiB  
Article
Predictive Values of Serum Chlamydia trachomatis TroA and HtrA IgG Antibodies as Markers of Persistent Infection in the Detection of Pelvic Adhesions and Tubal Occlusion
by Tiina Rantsi, Jolande A. Land, Päivi Joki-Korpela, Sander Ouburg, Kati Hokynar, Jorma Paavonen, Aila Tiitinen and Mirja Puolakkainen
Microorganisms 2019, 7(10), 391; https://doi.org/10.3390/microorganisms7100391 - 25 Sep 2019
Cited by 9 | Viewed by 2950
Abstract
Chlamydia trachomatis IgG antibody testing (CAT) has been used as a screening test for tubal factor infertility (TFI), but as the CAT is only a marker of a past exposure to C. trachomatis and not of late sequelae, the positive predictive value (PPV) [...] Read more.
Chlamydia trachomatis IgG antibody testing (CAT) has been used as a screening test for tubal factor infertility (TFI), but as the CAT is only a marker of a past exposure to C. trachomatis and not of late sequelae, the positive predictive value (PPV) of the test is low. The persistence of C. trachomatis in the upper genital tract has been suggested as one of the key mechanisms in the development of TFI. Serum antibodies against C. trachomatis TroA and HtrA, proteins expressed specifically during persistent infection, have been suggested as novel biomarkers for TFI diagnostics. We studied serum IgG antibody responses against C. trachomatis TroA, HtrA and MOMP in 79 subfertile women, of whom 28 had laparoscopically proven TFI. We confirmed that the accuracy of CAT in diagnosing TFI is low, whereas TroA IgG and HtrA IgG are more accurate tests in detecting tubal occlusion and pelvic adhesions. However, the sensitivity and negative predictive value (NPV) of TroA IgG and HtrA IgG are still too low to justify their use as a screening test in clinical practice. Individual immunogenetic profiles combined with TroA and HtrA antibody responses might identify women with the highest risk for developing late complications after C. trachomatis infection. Full article
(This article belongs to the Special Issue Chlamydiae and Chlamydia like Bacteria)
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12 pages, 1354 KiB  
Article
The Finnish New Variant of Chlamydia trachomatis with a Single Nucleotide Polymorphism in the 23S rRNA Target Escapes Detection by the Aptima Combo 2 Test
by Kati Hokynar, Kaisu Rantakokko-Jalava, Antti Hakanen, Marika Havana, Laura Mannonen, Pia Jokela, Satu Kurkela, Maija Lappalainen, Magnus Unemo and Mirja Puolakkainen
Microorganisms 2019, 7(8), 227; https://doi.org/10.3390/microorganisms7080227 - 31 Jul 2019
Cited by 18 | Viewed by 4796
Abstract
In 2019, more than 200 cases of Chlamydia trachomatis negative/equivocal by the Aptima Combo 2 assay (AC2, target: 23S rRNA) with slightly elevated relative light units (RLUs), but positive by the Aptima Chlamydia trachomatis assay (ACT, target: 16S rRNA) have been detected in [...] Read more.
In 2019, more than 200 cases of Chlamydia trachomatis negative/equivocal by the Aptima Combo 2 assay (AC2, target: 23S rRNA) with slightly elevated relative light units (RLUs), but positive by the Aptima Chlamydia trachomatis assay (ACT, target: 16S rRNA) have been detected in Finland To identify the cause of the AC2 CT false-negative specimens, we sequenced parts of the CT 23S rRNA gene in 40 specimens that were AC2 negative/equivocal but ACT positive. A single nucleotide polymorphism (SNP; C1515T in the C. trachomatis 23S rRNA gene) was revealed in 39 AC2/ACT discordant specimens. No decrease in the number of mandatorily notified C. trachomatis cases was observed nationally in Finland in 2010–2019. When RLUs obtained for AC2 negative specimens were retrospectively evaluated in 2011–2019, a continuous increase in the proportion of samples with RLUs 10–19 was observed since 2014, and a slight increase in the proportion of samples with RLUs 20–84 in 2017–2019, indicating that the Finnish new variant of C. trachomatis might have been spreading nationally for several years. This emphasizes that careful surveillance of epidemiology, positivity rate and test performance are mandatory to detect any changes affecting detection of infections. Full article
(This article belongs to the Special Issue Chlamydiae and Chlamydia like Bacteria)
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11 pages, 710 KiB  
Article
Transcriptional Expression of the ompA, cpaf, tarp, and tox Genes of Chlamydia trachomatis Clinical Isolates at Different Stages of the Developmental Cycle
by Suvi Korhonen, Kati Hokynar, Laura Mannonen, Jorma Paavonen, Eija Hiltunen-Back and Mirja Puolakkainen
Microorganisms 2019, 7(6), 153; https://doi.org/10.3390/microorganisms7060153 - 28 May 2019
Cited by 5 | Viewed by 2946
Abstract
The transcriptional gene expression patterns of Chlamydia trachomatis have mainly been studied using reference strains propagated in cultured cells. Here, using five low-passage-number C. trachomatis clinical isolates that originated from asymptomatic or symptomatic female patients, the in vitro expression of the ompA, [...] Read more.
The transcriptional gene expression patterns of Chlamydia trachomatis have mainly been studied using reference strains propagated in cultured cells. Here, using five low-passage-number C. trachomatis clinical isolates that originated from asymptomatic or symptomatic female patients, the in vitro expression of the ompA, cpaf, tarp, and tox genes was studied with reverse transcriptase real-time PCR during the chlamydial developmental cycle. We observed dissimilarities in the gene expression patterns between the low-passage-number clinical isolates and the reference strains. The expression of ompA and the peak of the tox expression were observed earlier in the reference strains than in most of the clinical isolates. The expression of cpaf was high in the reference strains compared with the clinical isolates at the mid-phase (6–24 hours post infection) of the developmental cycle. All of the strains had a rather similar tarp expression profile. Four out of five clinical isolates exhibited slower growth kinetics compared with the reference strains. The use of low-passage-number C. trachomatis clinical isolates instead of reference strains in the studies might better reflect the situation in human infection. Full article
(This article belongs to the Special Issue Chlamydiae and Chlamydia like Bacteria)
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13 pages, 2871 KiB  
Article
The Chlamydia trachomatis Extrusion Exit Mechanism Is Regulated by Host Abscission Proteins
by Meghan Zuck and Kevin Hybiske
Microorganisms 2019, 7(5), 149; https://doi.org/10.3390/microorganisms7050149 - 25 May 2019
Cited by 6 | Viewed by 4033
Abstract
The cellular exit strategies of intracellular pathogens have a direct impact on microbial dissemination, transmission, and engagement of immune responses of the host. Chlamydia exit their host via a budding mechanism called extrusion, which offers protective benefits to Chlamydia as they navigate their [...] Read more.
The cellular exit strategies of intracellular pathogens have a direct impact on microbial dissemination, transmission, and engagement of immune responses of the host. Chlamydia exit their host via a budding mechanism called extrusion, which offers protective benefits to Chlamydia as they navigate their extracellular environment. Many intracellular pathogens co-opt cellular abscission machinery to facilitate cell exit, which is utilized to perform scission of two newly formed daughter cells following mitosis. Similar to viral budding exit strategies, we hypothesize that an abscission-like mechanism is required to physically sever the chlamydial extrusion from the host cell, co-opting the membrane fission activities of the endosomal sorting complex required for transport (ESCRT) family of proteins that are necessary for cellular scission events, including abscission. To test this, C. trachomatis L2-infected HeLa cells were depleted of key abscission machinery proteins charged multivesicle body protein 4b (CHMP4B), ALIX, centrosome protein 55 (CEP55), or vacuolar protein sorting-associated protein 4A (VPS4A), using RNA interference (RNAi). Over 50% reduction in extrusion formation was achieved by depletion of CHMP4B, VPS4A, and ALIX, but no effect on extrusion was observed with CEP55 depletion. These results demonstrate a role for abscission machinery in C. trachomatis extrusion from the host cell, with ALIX, VPS4A and CHMP4B playing key functional roles in optimal extrusion release. Full article
(This article belongs to the Special Issue Chlamydiae and Chlamydia like Bacteria)
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9 pages, 474 KiB  
Article
Parachlamydia acanthamoebae Detected during a Pneumonia Outbreak in Southeastern Finland, in 2017–2018
by Kati Hokynar, Satu Kurkela, Tea Nieminen, Harri Saxen, Eero J. Vesterinen, Laura Mannonen, Risto Pietikäinen and Mirja Puolakkainen
Microorganisms 2019, 7(5), 141; https://doi.org/10.3390/microorganisms7050141 - 17 May 2019
Cited by 7 | Viewed by 2940
Abstract
Community-acquired pneumonia (CAP) is a common disease responsible for significant morbidity and mortality. However, the definite etiology of CAP often remains unresolved, suggesting that unknown agents of pneumonia remain to be identified. The recently discovered members of the order Chlamydiales, Chlamydia-related bacteria (CRB), [...] Read more.
Community-acquired pneumonia (CAP) is a common disease responsible for significant morbidity and mortality. However, the definite etiology of CAP often remains unresolved, suggesting that unknown agents of pneumonia remain to be identified. The recently discovered members of the order Chlamydiales, Chlamydia-related bacteria (CRB), are considered as possible emerging agents of CAP. Parachlamydia acanthamoebae is the most studied candidate. It survives and replicates inside free-living amoeba, which it might potentially use as a vehicle to infect animals and humans. A Mycoplasma pneumoniae outbreak was observed in Kymenlaakso region in Southeastern Finland during August 2017–January 2018. We determined the occurrence of Chlamydiales bacteria and their natural host, free-living amoeba in respiratory specimens collected during this outbreak with molecular methods. Altogether, 22/278 (7.9%) of the samples contained Chlamydiales DNA. By sequence analysis, majority of the CRBs detected were members of the Parachlamydiaceae family. Amoebal DNA was not detected within the sample material. Our study further proposes that Parachlamydiaceae could be a potential agent causing atypical CAP in children and adolescents. Full article
(This article belongs to the Special Issue Chlamydiae and Chlamydia like Bacteria)
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Review

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16 pages, 639 KiB  
Review
Chronic Inflammatory Diseases at Secondary Sites Ensuing Urogenital or Pulmonary Chlamydia Infections
by Yi Ying Cheok, Chalystha Yie Qin Lee, Heng Choon Cheong, Chung Yeng Looi and Won Fen Wong
Microorganisms 2020, 8(1), 127; https://doi.org/10.3390/microorganisms8010127 - 17 Jan 2020
Cited by 11 | Viewed by 3934
Abstract
Chlamydia trachomatis and C. pneumoniae are members of the Chlamydiaceae family of obligate intracellular bacteria. The former causes diseases predominantly at the mucosal epithelial layer of the urogenital or eye, leading to pelvic inflammatory diseases or blindness; while the latter is a major [...] Read more.
Chlamydia trachomatis and C. pneumoniae are members of the Chlamydiaceae family of obligate intracellular bacteria. The former causes diseases predominantly at the mucosal epithelial layer of the urogenital or eye, leading to pelvic inflammatory diseases or blindness; while the latter is a major causative agent for pulmonary infection. On top of these well-described diseases at the respective primary infection sites, Chlamydia are notoriously known to migrate and cause pathologies at remote sites of a host. One such example is the sexually acquired reactive arthritis that often occurs at few weeks after genital C. trachomatis infection. C. pneumoniae, on the other hand, has been implicated in an extensive list of chronic inflammatory diseases which include atherosclerosis, multiple sclerosis, Alzheimer’s disease, asthma, and primary biliary cirrhosis. This review summarizes the Chlamydia infection associated diseases at the secondary sites of infection, and describes the potential mechanisms involved in the disease migration and pathogenesis. Full article
(This article belongs to the Special Issue Chlamydiae and Chlamydia like Bacteria)
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21 pages, 1056 KiB  
Review
Chlamydiae from Down Under: The Curious Cases of Chlamydial Infections in Australia
by Martina Jelocnik
Microorganisms 2019, 7(12), 602; https://doi.org/10.3390/microorganisms7120602 - 22 Nov 2019
Cited by 13 | Viewed by 5947
Abstract
In Australia, the most researched and perhaps the most successful chlamydial species are the human pathogen Chlamydia trachomatis, animal pathogens Chlamydia pecorum and Chlamydia psittaci. C. trachomatis remains the leading cause of sexually transmitted infections in Australians and trachoma in Australian [...] Read more.
In Australia, the most researched and perhaps the most successful chlamydial species are the human pathogen Chlamydia trachomatis, animal pathogens Chlamydia pecorum and Chlamydia psittaci. C. trachomatis remains the leading cause of sexually transmitted infections in Australians and trachoma in Australian Indigenous populations. C. pecorum is globally recognised as the infamous koala and widespread livestock pathogen, whilst the avian C. psittaci is emerging as a horse pathogen posing zoonotic risks to humans. Certainly not innocuous, the human infections with Chlamydia pneumoniae seem to be less prevalent that other human chlamydial pathogens (namely C. trachomatis). Interestingly, the complete host range for C. pecorum and C. psittaci remains unknown, and infections by other chlamydial organisms in Australian domesticated and wildlife animals are understudied. Considering that chlamydial organisms can be encountered by either host at the human/animal interface, I review the most recent findings of chlamydial organisms infecting Australians, domesticated animals and native wildlife. Furthermore, I also provide commentary from leading Australian Chlamydia experts on challenges and future directions in the Chlamydia research field. Full article
(This article belongs to the Special Issue Chlamydiae and Chlamydia like Bacteria)
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17 pages, 287 KiB  
Review
Chlamydiaceae: Diseases in Primary Hosts and Zoonosis
by Heng Choon Cheong, Chalystha Yie Qin Lee, Yi Ying Cheok, Grace Min Yi Tan, Chung Yeng Looi and Won Fen Wong
Microorganisms 2019, 7(5), 146; https://doi.org/10.3390/microorganisms7050146 - 24 May 2019
Cited by 68 | Viewed by 6328
Abstract
Bacteria of the Chlamydiaceae family are a type of Gram-negative microorganism typified by their obligate intracellular lifestyle. The majority of the members in the Chlamydiaceae family are known pathogenic organisms that primarily infect the host mucosal surfaces in both humans and animals. For [...] Read more.
Bacteria of the Chlamydiaceae family are a type of Gram-negative microorganism typified by their obligate intracellular lifestyle. The majority of the members in the Chlamydiaceae family are known pathogenic organisms that primarily infect the host mucosal surfaces in both humans and animals. For instance, Chlamydia trachomatis is a well-known etiological agent for ocular and genital sexually transmitted diseases, while C. pneumoniae has been implicated in community-acquired pneumonia in humans. Other chlamydial species such as C. abortus, C. caviae, C. felis, C. muridarum, C. pecorum, and C. psittaci are important pathogens that are associated with high morbidities in animals. Importantly, some of these animal pathogens have been recognized as zoonotic agents that pose a significant infectious threat to human health through cross-over transmission. The current review provides a succinct recapitulation of the characteristics as well as transmission for the previously established members of the Chlamydiaceae family and a number of other recently described chlamydial organisms. Full article
(This article belongs to the Special Issue Chlamydiae and Chlamydia like Bacteria)
16 pages, 535 KiB  
Review
Chlamydia trachomatis and Chlamydia pneumoniae Interaction with the Host: Latest Advances and Future Prospective
by Marisa Di Pietro, Simone Filardo, Silvio Romano and Rosa Sessa
Microorganisms 2019, 7(5), 140; https://doi.org/10.3390/microorganisms7050140 - 16 May 2019
Cited by 32 | Viewed by 7303
Abstract
Research in Chlamydia trachomatis and Chlamydia pneumoniae has gained new traction due to recent advances in molecular biology, namely the widespread use of the metagenomic analysis and the development of a stable genomic transformation system, resulting in a better understanding of Chlamydia pathogenesis. [...] Read more.
Research in Chlamydia trachomatis and Chlamydia pneumoniae has gained new traction due to recent advances in molecular biology, namely the widespread use of the metagenomic analysis and the development of a stable genomic transformation system, resulting in a better understanding of Chlamydia pathogenesis. C. trachomatis, the leading cause of bacterial sexually transmitted diseases, is responsible of cervicitis and urethritis, and C. pneumoniae, a widespread respiratory pathogen, has long been associated with several chronic inflammatory diseases with great impact on public health. The present review summarizes the current evidence regarding the complex interplay between C. trachomatis and host defense factors in the genital micro-environment as well as the key findings in chronic inflammatory diseases associated to C. pneumoniae. Full article
(This article belongs to the Special Issue Chlamydiae and Chlamydia like Bacteria)
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Other

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11 pages, 837 KiB  
Case Report
An Asymptomatic Patient with Fatal Infertility Carried a Swedish Strain of Chlamydia trachomatis with Additional Deletion in The Plasmid orf1 that Belonged to A Different MLST Sequence Type
by Valentina A. Feodorova, Sergey S. Zaitsev, Yury V. Saltykov, Edgar S. Sultanakhmedov, Andrew L. Bakulev, Sergey S. Ulyanov and Vladimir L. Motin
Microorganisms 2019, 7(7), 187; https://doi.org/10.3390/microorganisms7070187 - 28 Jun 2019
Cited by 5 | Viewed by 2907
Abstract
Here, we present the first case of asymptomatic genital Chlamydial infection caused by the new emerging Chlamydia trachomatis (C.t.) ST13 strain genovar E, which has a double deletion of 377 bp and 17 bp in orf1 gene of the cryptic plasmid [...] Read more.
Here, we present the first case of asymptomatic genital Chlamydial infection caused by the new emerging Chlamydia trachomatis (C.t.) ST13 strain genovar E, which has a double deletion of 377 bp and 17 bp in orf1 gene of the cryptic plasmid (ddCT). This case occurred in an infertile patient (case-patient) with a detectable level of Chlamydial antibodies and a spermatozoa deficiency known as azoospermia. Additionally, the ddCT strain showed the presence of a duplication of 44 bp in the plasmid orf3 and SNP in orf4, which were known as the typical characteristics of the Swedish variant of C.t. (nvCT) genovar E. Multilocus sequence typing (MLST) determined a significant difference between ddCT and nvCT in four alleles (oppA, hfiX, gitA and enoA). Both ddCT and nvCT were assigned to different genetic lineages and could be allocated to two different non-overlapping clonal complexes. Furthermore, ddCT demonstrated a considerable difference among 4–5 alleles in comparison with other C.t. strains of genovar E of ST4, ST8, ST12, and ST94, including the founder of a single relevant cluster, wtCT E/SW3 (Swedish genetic lineage). In contrast to other genovar E strains, ddCT had identical alleles with seven out of seven loci found in ST13 strains of genovars D and G, including the founder for this clonal group, D/UW-3/CX, and six out of seven loci found in its derivatives, such as ST6, ST10, and ST95 of genovars G and H. Nevertheless, MSTree V2 showed that ddCT and nvCT could have a common early ancestor, which is a parental C.t. G/9301 strain of ST9. A significant difference between ddCT and nvCT of genovar D (nvCT-D) that was recently found in Mexico was also determined as: (i) ddCT belonged to genovar E but not to genovar D; (ii) ddCT had a 44 bp duplication within the orf3 of the plasmid typical for nvCT; (iii) ddCT possessed an additional 17 bp deletion in the orf1. In conclusion, improved case management should include the clinical physician’s awareness of the need to enhance molecular screening of asymptomatic Chlamydia patients. Such molecular diagnostics might be essential to significantly reducing the global burden of Chlamydial infection on international public health. Full article
(This article belongs to the Special Issue Chlamydiae and Chlamydia like Bacteria)
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5 pages, 193 KiB  
Case Report
A Bird’s-Eye View of Chronic Unilateral Conjunctivitis: Remember about Chlamydia psittaci
by Stien Vandendriessche, Joanna Rybarczyk, Pieter-Paul Schauwvlieghe, Geraldine Accou, Anne-Marie Van den Abeele and Daisy Vanrompay
Microorganisms 2019, 7(5), 118; https://doi.org/10.3390/microorganisms7050118 - 30 Apr 2019
Cited by 6 | Viewed by 2474
Abstract
Chlamydia psittaci causes psittacosis in humans, mainly in people in contact with birds in either the setting of occupational or companion bird exposure. Infection is associated with a range of clinical manifestations from asymptomatic infection to severe atypical pneumonia and systemic disease. C. [...] Read more.
Chlamydia psittaci causes psittacosis in humans, mainly in people in contact with birds in either the setting of occupational or companion bird exposure. Infection is associated with a range of clinical manifestations from asymptomatic infection to severe atypical pneumonia and systemic disease. C. psittaci has also been associated with ocular adnexal lymphoma in human patients. The current paper describes successful doxycycline treatment of a male patient suffering from C. psittaci chronic unilateral conjunctivitis, most probably linked to the visit of a South African wildlife reserve. Increased awareness among general and occupational physicians, ophthalmologists, clinicians, and the public on the potential of C. psittaci to cause ocular infection is needed. Full article
(This article belongs to the Special Issue Chlamydiae and Chlamydia like Bacteria)
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