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2.
Clin Lab ; 70(7)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38965951

RESUMO

BACKGROUND: Sexually transmitted infections (STIs) increase gradually and have become a public health problem in the world. UU, CT, NG, and MG are four common STI pathogens. Our retrospective study analyzed the clinical situation and the laboratory data of patients infected with the four pathogens. The prevalence of the four pathogens, detected in urine and genital tract secretion, was studied in Hangzhou, China. METHODS: A total of 3,168 male and female patients were randomly selected from February 2023 to February 2024. Urine and genital secretions were collected, and four STI pathogens were controlled for detection. Data were collected from the hospital's electronic medical records, and SPSS 25.0 software was used to perform a statistical analysis. RESULTS: Among 3,168 patients, a total of 1,527 were detected as positive, and the positive rate was 48.20%. The age of patients ranged from 13 - 98 years, with an average age of 45.6. The total of patients consisted of 2,191 males and 977 females, which had a significant difference (p < 0.05). Specimens were mainly collected from the Department of Dermatovenerology, Urological Surgery, Obstetrics and Gynecology, and so on. The positive rate was statistically different between male and female patients (p < 0.05). Single infection performed a main role and accounted for 79.57% of all of the positive patients. In the ≤ 20 age group, the positive rate was the highest and was as high as 77.65%. In detail, single infection caused by UU dominated, especially in the 21 - 30 age group. Double infection caused by UU and CT and triple infection caused by UU, CT, and NG were the majority, both especially in the 21 - 30 age group. There were significant differences in the positive rates in the different age groups and in the four pathogens (p < 0.05). Quadruple infection was very rare and had only been detected in one patient. CONCLUSIONS: The prevalence of the four pathogens in Hangzhou was different from other regions. More male than female patients, more single than multiple infections, and more single and multiple infections occurring in young people were the features in Hangzhou. The study would provide reference for prevention, diagnosis, and treatment of STI.


Assuntos
Infecções Sexualmente Transmissíveis , Humanos , Masculino , Feminino , China/epidemiologia , Adulto , Pessoa de Meia-Idade , Adolescente , Prevalência , Adulto Jovem , Estudos Retrospectivos , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/urina , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/microbiologia , Idoso , Idoso de 80 Anos ou mais , Gonorreia/epidemiologia , Gonorreia/diagnóstico , Gonorreia/urina , Gonorreia/microbiologia , Infecções por Chlamydia/epidemiologia , Infecções por Chlamydia/urina , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/microbiologia
3.
J Clin Microbiol ; 62(7): e0031124, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38836570

RESUMO

Home sample collection for sexually transmitted infection (STI) screening options can improve access to sexual healthcare across communities. For Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG), genital infections have classically been the focus for remote collection options. However, infections may go undiagnosed if sampling is limited to urogenital sites because some individuals only participate in oral and/or anal intercourse. Here we evaluated samples for CT/NG detection after several pre-analytical collection challenges. A paired provider to self-collection validation was performed on rectal [n = 162; 22 + for CT and 9 + for NG by provider-collected (PC)] and throat (N = 158; 2 + for CT and 11 + for NG by provider-collected) swabs. The positive percent agreement for CT and NG ranged from 90.9% to 100%. The discrepancies were more often positive on self-collected (SC) (n = 9 SC+/PC-; n = 1 PC+/SC-; n = 1 PC+/SC Equiv.; n = 2 PC-/SC Equiv.). An empirical limit of detection (LoD) lower than the manufacturer's claim (0.031 vs 2.5 IFU/mL for CT and 0.063 vs 124.8 CFU/ml for NG, respectively) was used to challenge additional variables. Common hand contaminants, including soap, hand sanitizer, lotion, and sunscreen were added to known positive (3× empirical LoD) or negative samples and did not influence detection. Samples at 2× and 10× the empirical LoD were challenged with extreme temperature cycling and extended room temperature storage. Detection was not affected by these conditions. These results indicate that remote self-collection is an appropriate method of sample acquisition for detecting extragenital CT/NG infections. Additionally, they provide a foundation towards meeting the regulatory standards for commercial testing of home collected extragenital samples. IMPORTANCE: There is a clinical need for expanded extragenital bacterial sexually transmitted infection (STI) testing options, but the current regulatory landscape limits the wide-spread promotion and adoption of such services. Improved access, particularly for the LGBTQ+ community, can be achieved by validating testing for specimens that are self-collected at a remote location and arrive at the laboratory via a postal carrier or other intermediary route. Here we provide valuable data showing that self-collected samples for anal and oropharyngeal STI testing are equally or increasingly sensitive compared with those collected by a provider. We systematically consider the effects of storage time, exposure to temperature extremes, and the addition of common toiletries on results.


Assuntos
Infecções por Chlamydia , Chlamydia trachomatis , Gonorreia , Neisseria gonorrhoeae , Manejo de Espécimes , Humanos , Manejo de Espécimes/métodos , Chlamydia trachomatis/isolamento & purificação , Gonorreia/diagnóstico , Gonorreia/microbiologia , Neisseria gonorrhoeae/isolamento & purificação , Feminino , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/microbiologia , Masculino , Adulto , Faringe/microbiologia , Infecções Sexualmente Transmissíveis/diagnóstico , Reto/microbiologia , Adulto Jovem , Sensibilidade e Especificidade
4.
J Neuroinflammation ; 21(1): 158, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879567

RESUMO

Respiratory infections are one of the most common causes of illness and morbidity in neonates worldwide. In the acute phase infections are known to cause wide-spread peripheral inflammation. However, the inflammatory consequences to the critical neural control centres for respiration have not been explored. Utilising a well characterised model of neonatal respiratory infection, we investigated acute responses within the medulla oblongata which contains key respiratory regions. Neonatal mice were intranasally inoculated within 24 h of birth, with either Chlamydia muridarum or sham-infected, and tissue collected on postnatal day 15, the peak of peripheral inflammation. A key finding of this study is that, while the periphery appeared to show no sex-specific effects of a neonatal respiratory infection, sex had a significant impact on the inflammatory response of the medulla oblongata. There was a distinct sex-specific response in the medulla coincident with peak of peripheral inflammation, with females demonstrating an upregulation of anti-inflammatory cytokines and males showing very few changes. Microglia also demonstrated sex-specificity with the morphology of females and males differing based upon the nuclei. Astrocytes showed limited changes during the acute response to neonatal infection. These data highlight the strong sex-specific impact of a respiratory infection can have on the medulla in the acute inflammatory phase.


Assuntos
Animais Recém-Nascidos , Infecções por Chlamydia , Chlamydia muridarum , Animais , Camundongos , Feminino , Infecções por Chlamydia/microbiologia , Infecções por Chlamydia/patologia , Masculino , Infecções Respiratórias/microbiologia , Infecções Respiratórias/patologia , Tronco Encefálico/patologia , Doenças Neuroinflamatórias/microbiologia , Doenças Neuroinflamatórias/patologia , Doenças Neuroinflamatórias/imunologia , Caracteres Sexuais , Camundongos Endogâmicos C57BL , Citocinas/metabolismo
5.
Vet Microbiol ; 295: 110128, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38851154

RESUMO

Feline upper respiratory tract disease (URTD) is a common but complicated disease that occurs in domestic cats, worldwide. 396 cats in Guangxi Province, China were screened for URTD-associated pathogens from March 2022 to August 2023. Mycoplasma felis was found to be the most prevalent infectious agent with a positivity rate of 24.75 %, followed by feline calicivirus (FCV), Chlamydia felis, feline herpesvirus 1 (FHV-1) and feline influenza A virus (FeIAV) with rates of 15.91, 11.62, 5.56 and 1.52 %, respectively. In particular, C. felis and M. felis were found in 13 of 55 co-infected cats. Of the 46 C. felis-positive samples, one strain, named as GXNN36, was successfully isolated using chicken embryos and it was characterized both in vivo and in vitro. For the cat studies, both high- and low-dose challenged groups showed severe conjunctivitis, accompanied by transient fever and respiratory symptoms. C. felis replicated well in turbinate, trachea and lung tissues with high copy numbers and the infection subsequently spread to the livers, spleens, pancreas, kidneys, hearts and intestines. These findings will help our understanding of the role of C. felis in feline URTD and provide a valuable model to evaluate the efficacy of vaccines and therapeutic remedies in the future.


Assuntos
Doenças do Gato , Infecções por Chlamydia , Chlamydia , Animais , Gatos , Doenças do Gato/microbiologia , Doenças do Gato/virologia , Chlamydia/isolamento & purificação , Chlamydia/genética , Chlamydia/patogenicidade , Chlamydia/classificação , Infecções por Chlamydia/veterinária , Infecções por Chlamydia/microbiologia , China/epidemiologia , Mycoplasma/isolamento & purificação , Mycoplasma/classificação , Infecções Respiratórias/veterinária , Infecções Respiratórias/microbiologia , Infecções Respiratórias/virologia , Calicivirus Felino/isolamento & purificação , Calicivirus Felino/patogenicidade , Coinfecção/veterinária , Coinfecção/microbiologia , Coinfecção/virologia , Feminino , Infecções por Mycoplasma/veterinária , Infecções por Mycoplasma/microbiologia , Masculino , Embrião de Galinha
6.
Front Cell Infect Microbiol ; 14: 1403782, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38912205

RESUMO

Introduction: We assessed the in vitro anti-chlamydial activity of fresh vaginal secretions, deciphering the microbial and metabolic components able to counteract Chlamydia trachomatis viability. Methods: Forty vaginal samples were collected from a group of reproductive-aged women and their anti-chlamydial activity was evaluated by inhibition experiments. Each sample underwent 16S rRNA metabarcoding sequencing to determine the bacterial composition, as well as 1H-NMR spectroscopy to detect and quantify the presence of vaginal metabolites. Results: Samples characterized by a high anti-chlamydial activity were enriched in Lactobacillus, especially Lactobacillus crispatus and Lactobacillus iners, while not-active samples exhibited a significant reduction of lactobacilli, along with higher relative abundances of Streptococcus and Olegusella. Lactobacillus gasseri showed an opposite behavior compared to L. crispatus, being more prevalent in not-active vaginal samples. Higher concentrations of several amino acids (i.e., isoleucine, leucine, and aspartate; positively correlated to the abundance of L. crispatus and L. jensenii) lactate, and 4-aminobutyrate were the most significant metabolic fingerprints of highly active samples. Acetate and formate concentrations, on the other hand, were related to the abundances of a group of anaerobic opportunistic bacteria (including Prevotella, Dialister, Olegusella, Peptostreptococcus, Peptoniphilus, Finegoldia and Anaerococcus). Finally, glucose, correlated to Streptococcus, Lachnospira and Alloscardovia genera, emerged as a key molecule of the vaginal environment: indeed, the anti-chlamydial effect of vaginal fluids decreased as glucose concentrations increased. Discussion: These findings could pave the way for novel strategies in the prevention and treatment of chlamydial urogenital infections, such as lactobacilli probiotic formulations or lactobacilli-derived postbiotics.


Assuntos
Chlamydia trachomatis , Lactobacillus , RNA Ribossômico 16S , Vagina , Feminino , Humanos , Vagina/microbiologia , RNA Ribossômico 16S/genética , Lactobacillus/isolamento & purificação , Lactobacillus/genética , Lactobacillus/metabolismo , Chlamydia trachomatis/isolamento & purificação , Adulto , Streptococcus/isolamento & purificação , Adulto Jovem , Lactobacillus crispatus/isolamento & purificação , Infecções por Chlamydia/microbiologia
7.
Nat Commun ; 15(1): 4926, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858371

RESUMO

Chlamydia invasion of epithelial cells is a pathogen-driven process involving two functionally distinct effectors - TarP and TmeA. They collaborate to promote robust actin dynamics at sites of entry. Here, we extend studies on the molecular mechanism of invasion by implicating the host GTPase dynamin 2 (Dyn2) in the completion of pathogen uptake. Importantly, Dyn2 function is modulated by TarP and TmeA at the levels of recruitment and activation through oligomerization, respectively. TarP-dependent recruitment requires phosphatidylinositol 3-kinase and the small GTPase Rac1, while TmeA has a post-recruitment role related to Dyn2 oligomerization. This is based on the rescue of invasion duration and efficiency in the absence of TmeA by the Dyn2 oligomer-stabilizing small molecule activator Ryngo 1-23. Notably, Dyn2 also regulated turnover of TarP- and TmeA-associated actin networks, with disrupted Dyn2 function resulting in aberrant turnover dynamics, thus establishing the interdependent functional relationship between Dyn2 and the effectors TarP and TmeA.


Assuntos
Actinas , Chlamydia trachomatis , Dinamina II , Chlamydia trachomatis/metabolismo , Chlamydia trachomatis/fisiologia , Humanos , Dinamina II/metabolismo , Dinamina II/genética , Células HeLa , Actinas/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Infecções por Chlamydia/microbiologia , Infecções por Chlamydia/metabolismo , Interações Hospedeiro-Patógeno , Células Epiteliais/microbiologia , Células Epiteliais/metabolismo
8.
Infect Immun ; 92(7): e0006324, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38899879

RESUMO

Toll-like receptor 9 (TLR9) is an innate immune receptor that localizes to endosomes in antigen presenting cells and recognizes single stranded unmethylated CpG sites on bacterial genomic DNA (gDNA). Previous bioinformatic studies have demonstrated that the genome of the human pathogen Chlamydia trachomatis contains TLR9 stimulatory motifs, and correlative studies have implied a link between human TLR9 (hTLR9) genotype variants and susceptibility to infection. Here, we present our evaluation of the stimulatory potential of C. trachomatis gDNA and its recognition by hTLR9- and murine TLR9 (mTLR9)-expressing cells. Utilizing reporter cell lines, we demonstrate that purified gDNA from C. trachomatis can stimulate hTLR9 signaling, albeit at lower levels than gDNA prepared from other Gram-negative bacteria. Interestingly, we found that while C. trachomatis is capable of signaling through hTLR9 and mTLR9 during live infections in HEK293 reporter cell lines, signaling only occurs at later developmental time points. Chlamydia-specific induction of hTLR9 is blocked when protein synthesis is inhibited prior to the RB-to-EB conversion, exacerbated by the inhibition of lipooligosaccharide biosynthesis, and is significantly altered during the induction of aberrance/persistence. Our observations support the hypothesis that chlamydial gDNA is released during the conversion between the pathogen's replicative and infectious forms and during treatment with antibiotics targeting peptidoglycan assembly. Given that C. trachomatis inclusions do not co-localize with TLR9-containing vacuoles in the pro-monocytic cell line U937, our findings also hint that chlamydial gDNA is capable of egress from the inclusion, and traffics to TLR9-containing vacuoles via an as yet unknown pathway.


Assuntos
Infecções por Chlamydia , Chlamydia trachomatis , Transdução de Sinais , Receptor Toll-Like 9 , Chlamydia trachomatis/imunologia , Chlamydia trachomatis/metabolismo , Chlamydia trachomatis/genética , Humanos , Receptor Toll-Like 9/metabolismo , Receptor Toll-Like 9/genética , Animais , Camundongos , Infecções por Chlamydia/microbiologia , Infecções por Chlamydia/imunologia , Infecções por Chlamydia/metabolismo , Células HEK293 , DNA Bacteriano/genética , Linhagem Celular
9.
PLoS Pathog ; 20(6): e1012303, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38885287

RESUMO

Chlamydia trachomatis is a clinically important bacterium that infects epithelial cells of the genitourinary and respiratory tracts and the eye. These differentiated cells are in a quiescent growth state and have a surface organelle called a primary cilium, but the standard Chlamydia cell culture infection model uses cycling cells that lack primary cilia. To investigate if these differences are relevant, we performed infections with host cells that have a primary cilium. We found that C. trachomatis caused progressive loss of the primary cilium that was prevented by disrupting Aurora A (AurA), HDAC6 or calmodulin, which are components of the cellular cilia disassembly pathway. Stabilization of the primary cilium by targeting this pathway caused a large reduction in infectious progeny although there were no changes in chlamydial inclusion growth, chlamydial replication or the ultrastructural appearance of dividing and infectious forms (RBs and EBs, respectively). Thus, the presence of a primary cilium interfered with the production of infectious EBs at a late step in the developmental cycle. C. trachomatis infection also induced quiescent cells to re-enter the cell cycle, as detected by EdU incorporation in S-phase, and Chlamydia-induced cilia disassembly was necessary for cell cycle re-entry. This study therefore describes a novel host-pathogen interaction in which the primary cilium limits a productive Chlamydia infection, and the bacterium counteracts this host cell defense by activating the cellular cilia disassembly pathway.


Assuntos
Infecções por Chlamydia , Chlamydia trachomatis , Cílios , Chlamydia trachomatis/fisiologia , Cílios/microbiologia , Cílios/metabolismo , Infecções por Chlamydia/microbiologia , Infecções por Chlamydia/metabolismo , Infecções por Chlamydia/patologia , Humanos , Células Epiteliais/microbiologia , Células Epiteliais/metabolismo
10.
PLoS One ; 19(6): e0305279, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38861585

RESUMO

OBJECTIVES: Chlamydia trachomatis (chlamydia) is one of the most reported bacterial sexually transmitted infections (STI) worldwide. Chlamydia can cause long term complications such as pelvic inflammatory disease (PID), ectopic pregnancy (EP) and tubal factor infertility (TFI). Changing testing strategies, for example reduced asymptomatic testing, influence chlamydia surveillance, highlighting the need for exploring alternative ways of monitoring chlamydia. We investigated the possibility of introducing routine surveillance of chlamydia related long term complications. METHODS: A qualitative study including 15 in-depth interviews with a purposive sample of gynaecologists, general practitioners (GP), sexual health and emergency doctors was conducted in the Netherlands in 2021-2022. A semi-structured interview guide focused on experiences with diagnosis and registration of PID, EP and TFI and how a change in asymptomatic chlamydia testing strategy might influence this. Interviews were transcribed and analysed using a thematic approach. RESULTS: Analysis showed that gynaecologists most frequently reported diagnosing PID, EP and TFI. Other professions rarely diagnose these complications, with emergency doctors only diagnosing EP. Most respondents reported unique registration codes for PID and EP, but the coding for TFI is more ambiguous. They reflected that diagnosis and registration of PID, EP and TFI are handled differently within their professions. Most respondents acknowledged registration in diagnostic codes as a useful surveillance tool. They expressed concerns in representativeness (e.g. differences in interpretation of diagnosis criteria) and data quality for surveillance. CONCLUSIONS: Patient files of gynaecologists are likely to be most complete for monitoring trends of diagnosed chlamydia related long term complications in the Netherlands. However, when establishing a chlamydia complication surveillance system, professionals should be engaged in further standardizing diagnosis and registration practices. This will improve the quality and interpretability of complication surveillance and facilitate comparison between countries.


Assuntos
Infecções por Chlamydia , Chlamydia trachomatis , Doença Inflamatória Pélvica , Humanos , Países Baixos/epidemiologia , Feminino , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/epidemiologia , Infecções por Chlamydia/microbiologia , Doença Inflamatória Pélvica/microbiologia , Doença Inflamatória Pélvica/epidemiologia , Doença Inflamatória Pélvica/diagnóstico , Chlamydia trachomatis/isolamento & purificação , Masculino , Pesquisa Qualitativa , Gravidez , Gravidez Ectópica/diagnóstico , Gravidez Ectópica/epidemiologia , Gravidez Ectópica/microbiologia , Adulto , Pessoa de Meia-Idade
11.
EBioMedicine ; 104: 105140, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38744110

RESUMO

BACKGROUND: Chlamydia trachomatis (CT) Major Outer Membrane Protein (MOMP) holds a neutralising epitope in the Variable Domain 4 (VD4), and this region's immune dominance during infection is well known. This study aimed to assess the antibody response induced after infection and compare it for specificity and functionality to the response following vaccination with the vaccine CTH522, which contains VD4's from serovars D, E, F, and G. METHODS: We assessed the antibody epitopes in MOMP by a high density peptide array. Furthermore, the role of the VD4 epitope in neutralisation was explored by competitive inhibition experiments with a fusion protein holding the neutralising VD4 linear epitope. This was done in two independent groups: 1) MOMP seropositive individuals infected with CT (n = 10, from case-control study) and 2) CTH522/CAF®01-vaccinated females (n = 14) from the CHLM-01 clinical trial. FINDINGS: We identified the major antigenic regions in MOMP as VD4 and the conserved region just before VD3 in individuals infected with CT. The same regions, with the addition of VD1, were identified in vaccine recipients. Overall, the VD4 peptide responses were uniform in vaccinated individuals and led to inhibition of infection in vitro in all tested samples, whereas the VD4 responses were more heterogenous in individuals infected with CT, and only 2 out of 10 samples had VD4-mediated neutralising antibody responses. INTERPRETATION: These data provide insights into the role of antibodies against MOMP VD4 induced after infection and vaccination, and show that their functionality differs. The induction of functional VD4-specific antibodies in vaccine recipients mimics previous results from animal models. FUNDING: This work was supported by the European Commission through contract FP7-HEALTH-2011.1.4-4-280873 (ADITEC) and Fonden til Lægevidenskabens Fremme.


Assuntos
Anticorpos Antibacterianos , Vacinas Bacterianas , Infecções por Chlamydia , Chlamydia trachomatis , Epitopos , Vacinação , Humanos , Chlamydia trachomatis/imunologia , Anticorpos Antibacterianos/imunologia , Anticorpos Antibacterianos/sangue , Infecções por Chlamydia/imunologia , Infecções por Chlamydia/microbiologia , Feminino , Vacinas Bacterianas/imunologia , Epitopos/imunologia , Anticorpos Neutralizantes/imunologia , Proteínas da Membrana Bacteriana Externa/imunologia , Adulto , Masculino , Estudos de Casos e Controles , Adulto Jovem
12.
J Biol Chem ; 300(6): 107350, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38718865

RESUMO

The obligate intracellular bacterium, Chlamydia trachomatis, has evolved to depend on its human host for many metabolites, including most amino acids and three of the four nucleotides. Given this, it is not surprising that depletion of a single amino acid in the host cell growth medium blocks chlamydial replication. Paradoxically, supra-normal levels of some amino acids also block productive replication of Chlamydia. Here, we have determined how elevated serine levels, generated by exogenous supplementation, impede chlamydial inclusion development and reduce the generation of infectious progeny. Our findings reveal that human serine racemase, which is broadly expressed in multiple tissues, potentiates the anti-chlamydial effect of elevated serine concentrations. In addition to reversibly converting l-serine to d-serine, serine racemase also deaminates serine via ß-elimination. We have determined that d-serine does not directly impact Chlamydia; rather, ammonia generated by serine deamination limits the productive chlamydial replication. Our findings imply that ammonia produced within host cells can traverse the chlamydial inclusion membrane. Further, this property of serine deaminase can be exploited to sensitize Chlamydia to concentrations of doxycycline that are otherwise not bactericidal. Because exogenously elevated levels of serine can be tolerated over extended periods, the broad expression pattern of serine racemase indicates it to be a host enzyme whose activity can be directed against multiple intracellular bacterial pathogens. From a therapeutic perspective, demonstrating host metabolism can be skewed to generate an anti-bacterial metabolite that synergizes with antibiotics, we believe our results provide a new approach to target intracellular pathogens.


Assuntos
Antibacterianos , Chlamydia trachomatis , Serina , Humanos , Chlamydia trachomatis/metabolismo , Chlamydia trachomatis/efeitos dos fármacos , Serina/metabolismo , Antibacterianos/farmacologia , Células HeLa , Racemases e Epimerases/metabolismo , Desaminação , Infecções por Chlamydia/metabolismo , Infecções por Chlamydia/tratamento farmacológico , Infecções por Chlamydia/microbiologia
13.
Pathog Dis ; 822024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38821518

RESUMO

Chlamydia trachomatis infection can be regulated by autophagy-related genes. LncRNA CYTOR has been proven to be involved in autophagy. In this research, we investigated the role of CYTOR in autophagy induced by C. trachomatis and the potential mechanisms. After C. trachomatis infection, CYTOR and MAPK1 were up-regulated and miR-206 was down-regulated, meanwhile, the autophagy-related protein Beclin1 and LC3-Ⅱ/LC3-Ⅰ ratio were increased. Interference with CYTOR or overexpression with miR-206 downregulated the autophagy-related protein Beclin1 and the number of autophagic spots LC3, decreased the protein ratio of LC3-II/LC3-I, and upregulated the expression of P62 protein. The luciferase reporter assay confirmed that CYTOR acted as a sponge for miR-206 to target MAPK1. In addition, CYTOR promoted autophagy induced by C. trachomatis infection through the MAPK1/ERK signaling pathway activation. Taken together, we have identified a novel molecular mechanism that the CYTOR/miR-206/MAPK1 axis was involved in the regulation of autophagy in C. trachomatis infection. This work provides an experimental basis for elucidating the pathogenesis of C. trachomatis for the treatment, prevention and control of related infectious diseases.


Assuntos
Autofagia , Chlamydia trachomatis , MicroRNAs , Proteína Quinase 1 Ativada por Mitógeno , RNA Longo não Codificante , Chlamydia trachomatis/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/genética , Infecções por Chlamydia/microbiologia , Infecções por Chlamydia/metabolismo , Células HeLa , Regulação para Cima , Proteína Beclina-1/metabolismo , Proteína Beclina-1/genética
14.
Microbiol Spectr ; 12(7): e0045324, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38814079

RESUMO

Chlamydia trachomatis is the leading cause of bacterial sexually transmitted infections in the USA and of preventable blindness worldwide. This obligate intracellular pathogen replicates within a membrane-bound inclusion, but how it acquires nutrients from the host while avoiding detection by the innate immune system is incompletely understood. C. trachomatis accomplishes this in part through the translocation of a unique set of effectors into the inclusion membrane, the inclusion membrane proteins (Incs). Incs are ideally positioned at the host-pathogen interface to reprogram host signaling by redirecting proteins or organelles to the inclusion. Using a combination of co-affinity purification, immunofluorescence confocal imaging, and proteomics, we characterize the interaction between an early-expressed Inc of unknown function, Tri1, and tumor necrosis factor receptor-associated factor 7 (TRAF7). TRAF7 is a multi-domain protein with a RING finger ubiquitin ligase domain and a C-terminal WD40 domain. TRAF7 regulates several innate immune signaling pathways associated with C. trachomatis infection and is mutated in a subset of tumors. We demonstrate that Tri1 and TRAF7 specifically interact during infection and that TRAF7 is recruited to the inclusion. We further show that the predicted coiled-coil domain of Tri1 is necessary to interact with the TRAF7 WD40 domain. Finally, we demonstrate that Tri1 displaces the native TRAF7 binding partners, mitogen-activated protein kinase kinase kinase 2 (MEKK2), and MEKK3. Together, our results suggest that by displacing TRAF7 native binding partners, Tri1 has the capacity to alter TRAF7 signaling during C. trachomatis infection.IMPORTANCEChlamydia trachomatis is the leading cause of bacterial sexually transmitted infections in the USA and preventable blindness worldwide. Although easily treated with antibiotics, the vast majority of infections are asymptomatic and therefore go untreated, leading to infertility and blindness. This obligate intracellular pathogen evades the immune response, which contributes to these outcomes. Here, we characterize the interaction between a C. trachomatis-secreted effector, Tri1, and a host protein involved in innate immune signaling, TRAF7. We identified host proteins that bind to TRAF7 and demonstrated that Tri1 can displace these proteins upon binding to TRAF7. Remarkably, the region of TRAF7 to which these host proteins bind is often mutated in a subset of human tumors. Our work suggests a mechanism by which Tri1 may alter TRAF7 signaling and has implications not only in the pathogenesis of C. trachomatis infections but also in understanding the role of TRAF7 in cancer.


Assuntos
Proteínas de Bactérias , Infecções por Chlamydia , Chlamydia trachomatis , Interações Hospedeiro-Patógeno , Humanos , Chlamydia trachomatis/metabolismo , Chlamydia trachomatis/genética , Chlamydia trachomatis/imunologia , Células HeLa , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Infecções por Chlamydia/microbiologia , Infecções por Chlamydia/metabolismo , Infecções por Chlamydia/imunologia , Transdução de Sinais , Peptídeos e Proteínas Associados a Receptores de Fatores de Necrose Tumoral/metabolismo , Peptídeos e Proteínas Associados a Receptores de Fatores de Necrose Tumoral/genética , Imunidade Inata , Ligação Proteica , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Células HEK293
15.
PLoS One ; 19(5): e0302785, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38768150

RESUMO

INTRODUCTION: The rates of gonorrhea and chlamydia have been increasing in the years preceding the COVID19 pandemic. Because most gonorrhea and chlamydia infections are located in the oropharynx and rectum for men who have sex with men (MSM), and because at-home self-collected swabs for these infections are not licensed by Health Canada or the United States Food and Drug Administration, decreased accessed to in-person care during and since the COVID19 pandemic potentially means missed case findings. OBJECTIVES: To evaluate the performance of at-home self-collected pharyngeal and rectal swabs for gonorrhea and chlamydia nucleic acid amplification testing. METHODOLOGY: All persons who contacted our Sexual Health Clinic and who had a clinical indication to complete oral and/or rectal swabs for gonorrhea and chlamydia were invited to complete at-home swabs in advance of their scheduled appointments. We mailed swabs and instructions to those who consented. Participants brought these swabs to their scheduled in clinic appointments, where we repeated the same swabs. All matching swabs were sent to the laboratory for analysis to determine concordance. RESULTS: From September 8, 2022 to July 18, 2023, we enrolled 296 eligible participants who provided 1184 swabs. For analysis, cancelled specimens and specimens with invalid results were excluded, leaving 1032 swabs for comparison. We identified 66 STI diagnoses in 47 unique participants. Overall accuracy was high (exceeding 99%), except for rectal chlamydia, which was 96.0%. While the performance of self-swabs for chlamydia was lower compared to gonorrhea, at-home swabs identified six chlamydia infections that were missed by in-clinic collected swabs (two pharyngeal, four rectal). Removing these six cases as "false positives" increased overall accuracy for chlamydia detection to 99.7% (pharyngeal) and 97.8% (rectal). CONCLUSION: Self-collected at-home swabs had good performance acceptable for gonorrhea and chlamydia nucleic acid amplification testing.


Assuntos
Infecções por Chlamydia , Chlamydia trachomatis , Gonorreia , Neisseria gonorrhoeae , Faringe , Reto , Manejo de Espécimes , Humanos , Chlamydia trachomatis/isolamento & purificação , Chlamydia trachomatis/genética , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/microbiologia , Gonorreia/diagnóstico , Gonorreia/microbiologia , Masculino , Neisseria gonorrhoeae/isolamento & purificação , Neisseria gonorrhoeae/genética , Reto/microbiologia , Faringe/microbiologia , Manejo de Espécimes/métodos , Adulto , Feminino , Técnicas de Amplificação de Ácido Nucleico/métodos , Homossexualidade Masculina , Pessoa de Meia-Idade , Autocuidado , Adulto Jovem
16.
Virulence ; 15(1): 2351234, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38773735

RESUMO

Chlamydia infection is an important cause of public health diseases, and no effective vaccine is currently available. Owing to its unique intracellular lifestyle, Chlamydia requires a variety of nutrients and substrates from host cells, particularly sphingomyelin, cholesterol, iron, amino acids, and the mannose-6-phosphate receptor, which are essential for inclusion development. Here, we summarize the recent advances in Chlamydia nutrient acquisition mechanism by hijacking host cell vesicular transport, which plays an important role in chlamydial growth and development. Chlamydia obtains the components necessary to complete its intracellular developmental cycle by recruiting Rab proteins (major vesicular trafficking regulators) and Rab effector proteins to the inclusion, interfering with Rab-mediated multivesicular trafficking, reorienting the nutrition of host cells, and reconstructing the intracellular niche environment. Consequently, exploring the role of vesicular transport in nutrient acquisition offers a novel perspective on new approaches for preventing and treating Chlamydia infection.


Assuntos
Infecções por Chlamydia , Chlamydia , Interações Hospedeiro-Patógeno , Nutrientes , Humanos , Infecções por Chlamydia/microbiologia , Infecções por Chlamydia/metabolismo , Chlamydia/metabolismo , Chlamydia/fisiologia , Chlamydia/patogenicidade , Nutrientes/metabolismo , Animais , Transporte Biológico
17.
Sci Rep ; 14(1): 11825, 2024 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-38783017

RESUMO

In the United States (US), chlamydia is the most frequently reported sexually transmitted infection that is nationally notifiable. We examined trends in chlamydia prevalence in the US in 2011-2016 compared with 2005-2010. Cross-sectional, nationally representative surveys, National Health and Nutrition Examination Surveys (NHANES), were used to compare national chlamydia prevalence estimates from 2011 to 2016 with those from 2005 to 2010, and changes in prevalence since 1999-2004 were also reviewed. Persons aged 18-39 years were included in these analyses. Prevalence of chlamydia was based on results from urine specimens. Results were weighted to represent the U.S. civilian, noninstitutionalized population. The baseline characteristics of the study population were similar in gender, age and race/ethnicity between the two groups (P > 0.05). The overall chlamydia prevalence was 1.88% (95% confidence interval [CI] 1.55-2.22%) in 2011-2016 and 1.57% (95% CI 1.27-1.87%) in 2005-2010, a relative increase of 19.7% (95% CI 0.2-39.2%; P < 0.05) between the two surveys. Increases in chlamydia prevalence was especially concentrated in persons who were male, aged 18 to 29 years, had > high school educational level, never married, age at first sex < 18 years, had 2-5 sexual partners in lifetime and had no past sexually transmitted diagnosis between 2005 and 2016 (P < 0.05). Multivariable logistic regression analysis demonstrated that chlamydia was more prevalent in those aged 18-29 years, being non-Hispanic Blacks, had high school educational level, being widowed/divorced/separated and had > 5 sexual partners. The chlamydia prevalence had an increasing trend from 2005-2010 to 2011-2016. Those with high chlamydia prevalence such as sexually active young adults and Non-Hispanic Black should be screened annually so that infected persons can be diagnosed and they and their sex partners can be treated promptly.


Assuntos
Infecções por Chlamydia , Humanos , Estados Unidos/epidemiologia , Infecções por Chlamydia/epidemiologia , Infecções por Chlamydia/microbiologia , Masculino , Feminino , Adulto , Adolescente , Prevalência , Adulto Jovem , Estudos Transversais , Inquéritos Nutricionais
18.
BMC Infect Dis ; 24(1): 480, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730346

RESUMO

BACKGROUND: Tubal factor infertility (TFI) is common in sub-Saharan Africa and often secondary to pelvic inflammatory disease (PID). Anaerobes associated with bacterial vaginosis (BV) are also found in PIDs widely dominated by Chlamydia trachomatis (C. trachomatis), whose role in TFI is better demonstrated than that of BV. OBJECTIVES: To determine the prevalence of BV and C. trachomatis and to investigate the association between BV, C. trachomatis and TFI. METHODS: We included 137 patients treated for infertility between January 2020 and November 2021. Cases were defined as women with infertility aged 18-45 years presenting with TFI (n = 52), and controls as infertile women in the same age groups without TFI (n = 85). Data on social habits, life style and infertility parameters were collected, and we performed screening for BV and C. trachomatis. Multiple regression was used to measure associations. RESULTS: The prevalence of BV and C. trachomatis was 42.3% (58/137) and 23.4% (32/137), respectively. BV (61.5% vs 30.6%, p<0.001) and C. trachomatis (48.1 vs 8.2%, p<0.001) were more frequent in cases of TFI. BV and C. trachomatis increased the risk of TFI approximately 4-fold [aOR: 3.77 (1.61-8.83), p=0.002] and 14-fold [aOR: 13.77 (4.59-41.27), p<0.001], respectively. CONCLUSION: BV and C. trachomatis infection are strongly associated with TFI in Bukavu. Prevention and screening should be implemented to reduce the risk of TFI.


Assuntos
Infecções por Chlamydia , Chlamydia trachomatis , Infertilidade Feminina , Vaginose Bacteriana , Humanos , Feminino , Adulto , Vaginose Bacteriana/epidemiologia , Vaginose Bacteriana/microbiologia , Vaginose Bacteriana/complicações , Chlamydia trachomatis/isolamento & purificação , Infecções por Chlamydia/epidemiologia , Infecções por Chlamydia/microbiologia , Infecções por Chlamydia/complicações , Prevalência , Adulto Jovem , Adolescente , República Democrática do Congo/epidemiologia , Pessoa de Meia-Idade , Infertilidade Feminina/microbiologia , Infertilidade Feminina/epidemiologia
19.
PLoS One ; 19(4): e0301873, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38578759

RESUMO

Men having sex with men (MSM) represent a key population, in which sexually transmitted rectal infections (STIs) caused by Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and high-risk HPV (HR-HPV) are very common and linked to significant morbidity. Investigating the anorectal microbiome associated with rectal STIs holds potential for deeper insights into the pathogenesis of these infections and the development of innovative control strategies. In this study, we explored the interplay at the rectal site between C. trachomatis, N. gonorrhoeae, HR-HPV infection, and the anorectal microbiome in a cohort of 92 MSM (47 infected by CT and/or NG vs 45 controls). Moreover, we assessed the presence of Torquetenovirus (TTV), a non-pathogenic endogenous virus, considered as a possible predictor of immune system activation. We found a high prevalence of HR-HPV rectal infections (61%), especially in subjects with a concurrent CT/NG rectal infection (70.2%) and in people living with HIV (84%). In addition, we observed that TTV was more prevalent in subjects with CT/NG rectal infections than in non-infected ones (70.2% vs 46.7%, respectively). The anorectal microbiome of patients infected by CT and/or NG exhibited a reduction in Escherichia, while the presence of TTV was significantly associated with higher levels of Bacteroides. We observed a positive correlation of HR-HPV types with Escherichia and Corynebacterium, and a negative correlation with the Firmicutes phylum, and with Prevotella, Oscillospira, Sutterella. Our findings shed light on some of the dynamics occurring within the rectal environment involving chlamydial/gonococcal infections, HPV, TTV, and the anorectal microbiome. These data could open new perspectives for the control and prevention of STIs in MSM.


Assuntos
Infecções por Chlamydia , Gonorreia , Infecções por HIV , Microbiota , Infecções por Papillomavirus , Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Masculino , Humanos , Neisseria gonorrhoeae , Chlamydia trachomatis , Homossexualidade Masculina , Gonorreia/epidemiologia , Gonorreia/microbiologia , Infecções por Chlamydia/complicações , Infecções por Chlamydia/epidemiologia , Infecções por Chlamydia/microbiologia , Prevalência , Infecções por HIV/epidemiologia
20.
Comp Med ; 74(2): 121-129, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561234

RESUMO

Chlamydia muridarum (Cm), an intracellular bacterium of historical importance, was recently rediscovered as moderately prevalent in research mouse colonies. Cm was first reported as a causative agent of severe pneumonia in mice about 80 y ago, and while it has been used experimentally to model Chlamydia trachomatis infection of humans, there have been no further reports of clinical disease associated with natural infection. We observed clinical disease and pathology in 2 genetically engi- neered mouse (GEM) strains, Il12rb2 KO and STAT1 KO, with impaired interferon-γ signaling and Th1 CD4+ T cell responses in a colony of various GEM strains known to be colonized with and shedding Cm. Clinical signs included poor condition, hunched posture, and poor fecundity. Histopathology revealed disseminated Cm with lesions in pulmonary, gastrointestinal, and urogenital tissues. The presence of Cm was confirmed using both immunohistochemistry for Cm major outer membrane protein-1 antigen and in situ hybridization using a target probe directed against select regions of Cm strain Nigg. Cm was also found in association with a urothelial papilloma in one mouse. These cases provide additional support for excluding Cm from research mouse colonies.


Assuntos
Infecções por Chlamydia , Chlamydia muridarum , Camundongos Knockout , Fator de Transcrição STAT1 , Animais , Infecções por Chlamydia/patologia , Infecções por Chlamydia/veterinária , Infecções por Chlamydia/microbiologia , Camundongos , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/metabolismo , Feminino , Receptores de Interleucina-12/deficiência , Receptores de Interleucina-12/genética , Masculino , Pneumopatias/microbiologia , Pneumopatias/patologia , Pneumopatias/veterinária
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