Search Results (15)

Chlamydia trachomatis (Ct) is a leading cause of sexually transmitted infections globally, often resulting in inflammatory disorders, ectopic pregnancies, and infertility. Studying Ct’s pathogenesis remains challenging due to its unique life cycle and host-specific interactions, which require diverse experimental models. Animal studies using mouse, guinea pig, pig, and non-human primate models provide valuable insights into immune responses, hormonal influences, and disease progression. However, they face limitations in terms of translational relevance due to physiological differences, as well as ethical concerns. Complementing these, in vitro systems, ranging from simple monolayer to advanced three-dimensional models, exhibit improved physiological relevance by replicating the human tissue architecture. This includes the detailed investigation of epithelial barrier disruptions, epithelium–stroma interactions, and immune responses at a cellular level. Nonetheless, in vitro models fall short in mimicking the intricate tissue structures found in vivo and, therefore, cannot faithfully replicate the host–pathogen interactions or infection dynamics observed in living organisms. This review presents a comprehensive overview of the in vivo and in vitro models employed over the past few decades to investigate Ct and its pathogenesis, addressing their strengths and limitations. Furthermore, we explore emerging technologies, including organ-on-chip and in silico models, as promising tools to overcome the existing challenges and refine our understanding of Ct infections. Full article

Chlamydia trachomatis (CT) is a major cause of sexually transmitted infections (STIs) worldwide, with significant implications for reproductive health. The bacterium’s genome contains highly polymorphic regions, influencing both the type and severity of infections. These genetic variations, particularly those occurring in the major outer membrane protein (MOMP) gene, are critical for classifying the bacterium into distinct serovars and enable CT to adapt to diverse host environments, contributing to its immune evasion, persistence, and pathogenicity. Persistent or untreated urogenital infections can lead to chronic inflammation, tissue damage, and pelvic inflammatory disease, ultimately increasing the risk of ectopic pregnancy, spontaneous abortion, and infertility. This review consolidates current knowledge on the genetic diversity of CT, its potential role in modulating infection outcomes, and its immune evasion mechanisms. By integrating scientific evidence linking chlamydial infections to infertility, we underscore the urgent need for targeted research to address this critical public health challenge. Full article

Chlamydia trachomatis (Ct) is an obligate intracellular pathogen that causes the most commonly diagnosed bacterial sexually transmitted infection (STI) and is a leading cause of preventable blindness globally. Ct infections can generate a strong pro-inflammatory immune response, leading to immune-mediated pathology in infected tissues. Neutrophils play an important role in mediating both pathology and protection during infection. Excessive neutrophil activation, migration, and survival are associated with host tissue damage during Chlamydia infections. In contrast, neutrophils also perform phagocytic killing of Chlamydia in the presence of IFN-γ and anti-Chlamydia antibodies. Neutrophil extracellular traps (NETs) and many neutrophil degranulation products have also demonstrated strong anti-Chlamydia functions. To counteract this neutrophil-mediated protection, Chlamydia has developed several evasion strategies. Various Chlamydia proteins can limit potentially protective neutrophil responses by directly targeting receptors present on the surface of neutrophils or neutrophil degranulation products. In this review, we provide a survey of current knowledge regarding the role of neutrophils in pathogenesis and protection, including the ways that Chlamydia circumvents neutrophil functions, and we propose critical areas for future research. Full article

Trachoma is the most common infectious cause of blindness worldwide. This review investigates the pathogenesis of trachoma, focusing on its causative agent, transmission pathways, disease progression, and immune responses. Trachoma is caused by serovars A–C of the bacterium Chlamydia trachomatis (Ct). Transmission occurs through direct or indirect exchanges of ocular and nasal secretions, especially in regions with poor hygiene and overcrowded living conditions. The disease is initiated in early childhood by repeated infection of the ocular surface by Ct. This triggers recurrent chronic inflammatory episodes, leading to the development of conjunctival scarring and potentially to trichiasis, corneal opacity, and visual impairment. Exploring the pathogenesis of trachoma not only unveils the intricate pathways and mechanisms underlying this devastating eye disease but also underscores the multifaceted dimensions that must be considered in its management. Full article

Epidemiologic studies have established that mpox (formerly known as monkeypox) outbreaks worldwide in 2022–2023, due to Clade IIb mpox virus (MPXV), disproportionately affected gay, bisexual, and other men who have sex with men. More than 35% and 40% of the mpox cases suffer from co-infection with HIV and sexually transmitted infections (STIs) (e.g., Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, and herpes simplex virus), respectively. Bacterial superinfection can also occur. Co-infection of MPXV and other infectious agents may enhance disease severity, deteriorate outcomes, elongate the recovery process, and potentially contribute to the morbidity and mortality of the ensuing diseases. However, the interplays between MPXV and HIV, bacteria, other STI pathogens and host cells are poorly studied. There are many open questions regarding the impact of co-infections with HIV, STIs, or bacterial superinfections on the diagnosis and treatment of MPXV infections, including clinical and laboratory-confirmed mpox diagnosis, suboptimal treatment effectiveness, and induction of antiviral drug resistance. In this review article, we will discuss the progress and knowledge gaps in MPXV biology, antiviral therapy, pathogenesis of human MPXV and its co-infection with HIV, STIs, or bacterial superinfections, and the impact of the co-infections on the diagnosis and treatment of mpox disease. This review not only sheds light on the MPXV infection and co-infection of other etiologies but also calls for more research on MPXV life cycles and the molecular mechanisms of pathogenesis of co-infection of MPXV and other infectious agents, as well as research and development of a novel multiplex molecular testing panel for the detection of MPXV and other STI co-infections. Full article

The incidence of Chlamydia trachomatis respiratory infection is increasing, and its pathogenesis is still unclear. Pyroptosis, as a mode of inflammatory cell death, plays a vital role in the occurrence and development of Chlamydia trachomatis respiratory infection. In this study, the potential pyroptosis-related genes involved in Chlamydia trachomatis respiratory infection were identified by constructing a mouse model of C. muridarum infection combined with bioinformatics analysis. Through in-depth analysis of the RNA sequencing data, 13 differentially expressed pyroptosis-related genes were screened, including 1 downregulated gene and 12 upregulated genes. Gene ontology (GO) analysis showed that these genes mainly regulate inflammatory responses and produce IL-1β. Protein–protein interaction network analysis identified eight hub genes of interest: Tnf, Tlr2, Il1b, Nlrp3, Tlr9, Mefv, Zbp1 and Tnfaip3. Through quantitative real-time PCR (qPCR) analysis, we found that the expression of these genes in the lungs of C. muridarum-infected mice was significantly reduced, consistent with the bioinformatics results. At the same time, we detected elevated levels of caspase-3, gasdermin D and gasdermin E proteins in the lungs of C. muridarum-infected mice, demonstrating that Chlamydia trachomatis infection does induce pyroptosis. We then predicted nine miRNAs targeting these hub genes and constructed a key competitive endogenous RNA (ceRNA) network. In summary, we identified six key pyroptosis-related genes involved in Chlamydia trachomatis respiratory infection and constructed a ceRNA network associated with these genes. These findings will improve understanding of the molecular mechanisms underlying pyroptosis in Chlamydia trachomatis respiratory infections. Full article

Currently, Chlamydia trachomatis still possesses a significant impact on public health, with more than 130 million new cases each year, alongside a high prevalence of asymptomatic infections (approximately 80% in women and 50% in men). C. trachomatis infection involves a wide range of different cell types, from cervical epithelial cells, testicular Sertoli cells to Synovial cells, leading to a broad spectrum of pathologies of varying severity both in women and in men. Several two-dimensional in vitro cellular models have been employed for investigating C. trachomatis host–cell interaction, although they present several limitations, such as the inability to mimic the complex and dynamically changing structure of in vivo human host-tissues. Here, we present a brief overview of the most cutting-edge three-dimensional cell-culture models that mimic the pathophysiology of in vivo human tissues and organs for better translating experimental findings into a clinical setting. Future perspectives in the field of C. trachomatis research are also provided. Full article

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

Chlamydia trachomatis (Ct) causes the most prevalent bacterial sexually transmitted disease leading to ectopic pregnancy and infertility. Swine not only have many similarities to humans, but they are also susceptible to Ct. Despite these benefits and the ease of access to primary tissue from this food animal, in vitro research in swine has been underutilized. This study will provide basic understanding of the Ct host–pathogen interactions in porcine oviduct epithelial cells (pOECs)—the counterparts of human Fallopian tube epithelial cells. Using NanoString technology, flow cytometry, and confocal and transmission-electron microscopy, we studied the Ct developmental cycle in pOECs, the cellular immune response, and the expression and location of the tight junction protein claudin-4. We show that Ct productively completes its developmental cycle in pOECs and induces an immune response to Ct similar to human cells: Ct mainly induced the upregulation of interferon regulated genes and T-cell attracting chemokines. Furthermore, Ct infection induced an accumulation of claudin-4 in the Ct inclusion with a coinciding reduction of membrane-bound claudin-4. Downstream effects of the reduced membrane-bound claudin-4 expression could potentially include a reduction in tight-junction expression, impaired epithelial barrier function as well as increased susceptibility to co-infections. Thereby, this study justifies the investigation of the effect of Ct on tight junctions and the mucosal epithelial barrier function. Taken together, this study demonstrates that primary pOECs represent an excellent in vitro model for research into Ct pathogenesis, cell biology and immunity. Full article

Pathogenic bacteria are a global health threat, with over 2 million infections caused by Gram-negative bacteria every year in the United States. This problem is exacerbated by the increase in resistance to common antibiotics that are routinely used to treat these infections, creating an urgent need for innovative ways to treat and prevent virulence caused by these pathogens. Many Gram-negative pathogenic bacteria use a type III secretion system (T3SS) to inject toxins and other effector proteins directly into host cells. The T3SS has become a popular anti-virulence target because it is required for pathogenesis and knockouts have attenuated virulence. It is also not required for survival, which should result in less selective pressure for resistance formation against T3SS inhibitors. In this review, we will highlight selected examples of direct antibody immunizations and the use of antibodies in immunotherapy treatments that target the bacterial T3SS. These examples include antibodies targeting the T3SS of Pseudomonas aeruginosa, Yersinia pestis, Escherichia coli, Salmonella enterica, Shigella spp., and Chlamydia trachomatis. Full article

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

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

The actin cytoskeleton is crucially important to maintenance of the cellular structure, cell motility, and endocytosis. Accordingly, bacterial pathogens often co-opt the actin-restructuring machinery of host cells to access or create a favorable environment for their own replication. The obligate intracellular organism Chlamydia trachomatis and related species exemplify this dynamic: by inducing actin polymerization at the site of pathogen-host attachment, Chlamydiae induce their own uptake by the typically non-phagocytic epithelium they infect. The interaction of chlamydial adhesins with host surface receptors has been implicated in this effect, as has the activity of the chlamydial effector TarP (translocated actin recruitment protein). Following invasion, C. trachomatis dynamically assembles and maintains an actin-rich cage around the pathogen’s membrane-bound replicative niche, known as the chlamydial inclusion. Through further induction of actin polymerization and modulation of the actin-crosslinking protein myosin II, C. trachomatis promotes egress from the host via extrusion of the inclusion. In this review, we present the experimental findings that can inform our understanding of actin-dependent chlamydial pathogenesis, discuss lingering questions, and identify potential avenues of future study. Full article

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

Background: Viral infections of the anal/rectal tract of men who have sex with men (MSM) have been poorly studied. Methods: In total, 158 swab samples (81 anal/rectal, 65 throat/oral and 12 urethral) were collected from 126 MSM. DNA was isolated and subjected to real-time PCR assays for the detection of the sexually transmitted (ST) pathogens Chlamydia trachomatis, Neisseria gonorrhoeae and Mycoplasmas ssp, human papillomavirus (HPV) and six human polyomaviruses (HPyVs; JCPyV, BKPyV, Merkel cell PyV–MCPyV-, HPyV-6, HPyV-7 and HPyV-9). Results: C. trachomatis (31/126, 24.6%) and M. genitalium (30/126, 23.8%) were the most frequently detected ST pathogens. Thirty-one/126 (24.6%) patients were positive for at least one HPyV. The significantly (p < 0.05) prevalent HPyV in the anal tract was MCPyV, which was amplified in 27/81 (33.3%) samples, followed by HPyV-6, which was amplified in 6/81 (7.4%) swabs. Coinfections with MCPyV and C. trachomatis or Mycoplasmas were found in 4/21 (19.0%) and 5/21 (23.8%) anal/rectal swabs, respectively. Three/4 MCPyV-C. trachomatis coinfected patients were symptomatic. Conclusions: Based on the high prevalence of MCPyV in the anal/rectal swabs from MSM patients and on the well-known oncogenic properties of MCPyV, sexual transmission and possible involvement of HPyVs in the pathogenesis of diseases of the anal canal should be further studied. Full article