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PLoS Pathogens May 2024Mycoplasmas are minimal but notorious bacteria that infect humans and animals. These genome-reduced organisms have evolved strategies to overcome host apoptotic defense...
Mycoplasmas are minimal but notorious bacteria that infect humans and animals. These genome-reduced organisms have evolved strategies to overcome host apoptotic defense and establish persistent infection. Here, using Mycoplasma bovis as a model, we demonstrate that mycoplasma glycine cleavage system (GCS) H protein (GcvH) targets the endoplasmic reticulum (ER) to hijack host apoptosis facilitating bacterial infection. Mechanically, GcvH interacts with the ER-resident kinase Brsk2 and stabilizes it by blocking its autophagic degradation. Brsk2 subsequently disturbs unfolded protein response (UPR) signaling, thereby inhibiting the key apoptotic molecule CHOP expression and ER-mediated intrinsic apoptotic pathway. CHOP mediates a cross-talk between ER- and mitochondria-mediated intrinsic apoptosis. The GcvH N-terminal amino acid 31-35 region is necessary for GcvH interaction with Brsk2, as well as for GcvH to exert anti-apoptotic and potentially pro-infective functions. Notably, targeting Brsk2 to dampen apoptosis may be a conserved strategy for GCS-containing mycoplasmas. Our study reveals a novel role for the conserved metabolic route protein GcvH in Mycoplasma species. It also sheds light on how genome-reduced bacteria exploit a limited number of genomic proteins to resist host cell apoptosis thereby facilitating pathogenesis.
Topics: Apoptosis; Humans; Endoplasmic Reticulum; Bacterial Proteins; Animals; Mycoplasma Infections; Mycoplasma bovis; Glycine; Unfolded Protein Response; Protein Serine-Threonine Kinases
PubMed: 38787906
DOI: 10.1371/journal.ppat.1012266 -
Marine Drugs May 2024, a notable pathogen behind respiratory infections, employs specialized proteins to adhere to the respiratory epithelium, an essential process for initiating infection....
, a notable pathogen behind respiratory infections, employs specialized proteins to adhere to the respiratory epithelium, an essential process for initiating infection. The role of glycosaminoglycans, especially heparan sulfate, is critical in facilitating pathogen-host interactions, presenting a strategic target for therapeutic intervention. In this study, we assembled a glycan library comprising heparin, its oligosaccharide derivatives, and a variety of marine-derived sulfated glycans to screen the potential inhibitors for the pathogen-host interactions. By using Surface Plasmon Resonance spectroscopy, we evaluated the library's efficacy in inhibiting the interaction between adhesion proteins and heparin. Our findings offer a promising avenue for developing novel therapeutic strategies against infections.
Topics: Mycoplasma pneumoniae; Heparin; Polysaccharides; Aquatic Organisms; Humans; Adhesins, Bacterial; Bacterial Adhesion; Pneumonia, Mycoplasma; Anti-Bacterial Agents; Animals; Host-Pathogen Interactions; Sulfates
PubMed: 38786623
DOI: 10.3390/md22050232 -
Biosensors May 2024Sexually transmitted diseases (STDs) are a global concern because approximately 1 million new cases emerge daily. Most STDs are curable, but if left untreated, they can...
Sexually transmitted diseases (STDs) are a global concern because approximately 1 million new cases emerge daily. Most STDs are curable, but if left untreated, they can cause severe long-term health implications, including infertility and even death. Therefore, a test enabling rapid and accurate screening and genotyping of STD pathogens is highly awaited. Herein, we present the development of the DNA-based 6STD Genotyping 9G Membrane test, a lateral flow strip membrane assay, for the detection and genotyping of six STD pathogens, including , , , , , and . Here, we developed a multiplex PCR primer set that allows PCR amplification of genomic materials for these six STD pathogens. We also developed the six ssDNA probes that allow highly efficient detection of the six STD pathogens. The 6STD Genotyping 9G Membrane test lets us obtain the final detection and genotyping results in less than 30 m after PCR at 25 °C. The accuracy of the 6STD Genotyping 9G membrane test in STD genotyping was confirmed by its 100% concordance with the sequencing results of 120 clinical samples. Therefore, the 6STD Genotyping 9G Membrane test emerges as a promising diagnostic tool for precise STD genotyping, facilitating informed decision-making in clinical practice.
Topics: Humans; Chlamydia trachomatis; Neisseria gonorrhoeae; Sexually Transmitted Diseases; Genotype; Trichomonas vaginalis; Genotyping Techniques; Mycoplasma hominis; Ureaplasma urealyticum; DNA; Mycoplasma genitalium; Biosensing Techniques; DNA, Bacterial; Multiplex Polymerase Chain Reaction
PubMed: 38785734
DOI: 10.3390/bios14050260 -
Journal of Clinical Virology : the... Aug 2024Community-acquired pneumonia (CAP) is a major global cause of death and hospitalization. Bacteria or community-acquired viruses (CARVs) cause CAP. COVID-19 associated...
BACKGROUND
Community-acquired pneumonia (CAP) is a major global cause of death and hospitalization. Bacteria or community-acquired viruses (CARVs) cause CAP. COVID-19 associated restrictions effectively reduced the circulation of CARVs.
OBJECTIVES
The aim of this study was to analyze the proportion of CARVs in adult patients with CAP from mid-2020 to mid-2023. Specifically, we aimed to compare the rate of influenza virus, SARS-CoV-2, and RSV detections in patients aged 18-59 years and ≥60 years.
STUDY DESIGN
We analyze the proportion of 21 community-acquired respiratory viruses (CARVs) and three atypical bacteria (Bordetella pertussis, Legionella pneumophila, and Mycoplasma pneumoniae) in nasopharyngeal swab samples using molecular multiplex methods within the prospective, multicentre, multinational study of the German study Group CAPNETZ. We used stringent inclusion criteria throughout the study.
RESULTS
We identified CARVs in 364/1,388 (26.2 %) patients. In detail, we detected SARS-CoV-2 in 210/1,388 (15.1 %), rhino-/enterovirus in 64/1,388 (4.6 %), influenza virus in 23/1,388 (1.6 %) and RSV in 17/1,388 (1.2 %) of all patients. We detected RSV and influenza more frequently in patients ≥60 years, especially in 22/23 compared to the previous season. None of the atypical bacteria were detected.
CONCLUSIONS
Beginning in 2023, we demonstrate a re-emergence of CARVs in CAP patients. Effective vaccines or specific antiviral therapies for more than two thirds of the detected viral infections are currently available. High detection rates of vaccine-preventable viruses in older age groups support targeted vaccination campaigns.
Topics: Humans; Community-Acquired Infections; Middle Aged; Adult; Prospective Studies; Male; Female; Young Adult; Adolescent; Aged; COVID-19; Mycoplasma pneumoniae; SARS-CoV-2; Pneumonia, Viral; Influenza, Human; Germany; Viruses; Nasopharynx; Legionella pneumophila
PubMed: 38781632
DOI: 10.1016/j.jcv.2024.105694 -
Health Informatics Journal 2024Mycoplasma pneumonia may lead to hospitalizations and pose life-threatening risks in children. The automated identification of mycoplasma pneumonia from electronic...
Mycoplasma pneumonia may lead to hospitalizations and pose life-threatening risks in children. The automated identification of mycoplasma pneumonia from electronic medical records holds significant potential for improving the efficiency of hospital resource allocation. In this study, we proposed a novel method for identifying mycoplasma pneumonia by integrating multi-modal features derived from both free-text descriptions and structured test data in electronic medical records. Our approach begins with the extraction of free-text and structured data from clinical records through a systematic preprocessing pipeline. Subsequently, we employ a pre-trained transformer language model to extract features from the free-text, while multiple additive regression trees are used to transform features from the structured data. An attention-based fusion mechanism is then applied to integrate these multi-modal features for effective classification. We validated our method using clinic records of 7157 patients, retrospectively collected for training and testing purposes. The experimental results demonstrate that our proposed multi-modal fusion approach achieves significant improvements over other methods across four key performance metrics.
Topics: Humans; Pneumonia, Mycoplasma; Electronic Health Records; Child; Retrospective Studies; Mycoplasma pneumoniae; Female; Male; Child, Preschool
PubMed: 38779978
DOI: 10.1177/14604582241255818 -
BMC Pulmonary Medicine May 2024Mycoplasma pneumoniae pneumonia (MPP) is prevalent in paediatric patients and can progress to refractory mycoplasma pneumoniae pneumonia (RMPP).
INTRODUCTION
Mycoplasma pneumoniae pneumonia (MPP) is prevalent in paediatric patients and can progress to refractory mycoplasma pneumoniae pneumonia (RMPP).
OBJECTIVE
To assess the predictive value of bronchoscopy combined with computed tomography (CT) score in identifying RMPP in children.
METHODS
A retrospective analysis was conducted on 244 paediatric patients with MP, categorising them into RMPP and general mycoplasma pneumoniae pneumonia (GMPP) groups. A paired t-test compared the bronchitis score (BS) and CT score before and after treatment, supplemented by receiver operating characteristic (ROC) analysis.
RESULTS
The RMPP group showed higher incidences of extrapulmonary complications and pleural effusion (58.10% and 40%, respectively) compared with the GMPP group (44.60%, p = 0.037 and 18.71%, p < 0.001, respectively). The CT scores for each lung lobe were statistically significant between the groups, except for the right upper lobe (p < 0.05). Correlation analysis between the total CT score and total BS yielded r = 0.346 and p < 0.001. The ROC for BS combined with CT score, including area under the curve, sensitivity, specificity, and cut-off values, were 0.82, 0.89, 0.64, and 0.53, respectively.
CONCLUSION
The combined BS and CT score method is highly valuable in identifying RMPP in children.
Topics: Humans; Pneumonia, Mycoplasma; Male; Female; Retrospective Studies; Child; Bronchoscopy; Tomography, X-Ray Computed; Child, Preschool; ROC Curve; Mycoplasma pneumoniae; Predictive Value of Tests; Anti-Bacterial Agents; Adolescent; Sensitivity and Specificity; Lung; Bronchitis
PubMed: 38778338
DOI: 10.1186/s12890-024-02996-w -
Veterinary Microbiology Jul 2024Mycoplasma synoviae causes infectious synovitis and respiratory tract infections in chickens and is responsible for significant economic losses in the poultry industry....
Mycoplasma synoviae causes infectious synovitis and respiratory tract infections in chickens and is responsible for significant economic losses in the poultry industry. Effective attachment and colonisation of the trachea is critical for the persistence of the organism and progression of the disease it causes. The respiratory tract infection is usually sub-clinical, but concurrent infection with infectious bronchitis virus (IBV) is known to enhance the pathogenicity of M. synoviae. This study aimed to explore differentially expressed genes in the tracheal mucosa, and their functional categories, during chronic infection with M. synoviae, using a M. synoviae-IBV infection model. The transcriptional profiles of the trachea were assessed 2 weeks after infection using RNA sequencing. In chickens infected with M. synoviae or IBV, only 1 or 8 genes were differentially expressed compared to uninfected chickens, respectively. In contrast, the M. synoviae-IBV infected chickens had 621 upregulated and 206 downregulated genes compared to uninfected chickens. Upregulated genes and their functional categories were suggestive of uncontrolled lymphoid cell proliferation and an ongoing pro-inflammatory response. Genes associated with anti-inflammatory effects, pathogen removal, apoptosis, regulation of the immune response, airway homoeostasis, cell adhesion and tissue regeneration were downregulated. Overall, transcriptional changes in the trachea, 2 weeks after infection with M. synoviae and IBV, indicate immune dysregulation, robust inflammation and a lack of cytotoxic damage during chronic infection. This model provides insights into the pathogenesis of chronic infection with M. synoviae.
Topics: Animals; Chickens; Mycoplasma Infections; Poultry Diseases; Mycoplasma synoviae; Trachea; Infectious bronchitis virus; Chronic Disease; Coronavirus Infections; Transcriptome; Gene Expression Profiling; Coinfection
PubMed: 38772075
DOI: 10.1016/j.vetmic.2024.110119 -
PloS One 2024Mycoplasmal pneumonia in sheep and goats usually result covert but huge economic losses in the sheep and goat industry. The disease is prevalent in various countries in...
Mycoplasmal pneumonia in sheep and goats usually result covert but huge economic losses in the sheep and goat industry. The disease is prevalent in various countries in Africa and Asia. Clinical manifestations in affected animals include anorexia, fever, and respiratory symptoms such as dyspnea, polypnea, cough, and nasal discharge. Due to similarities with other respiratory infections, accurate diagnosis can be challenging, and isolating the causative organism is often problematic. However, the utilization of molecular techniques, such as PCR, allows for rapid and specific identification of pathogens. Thus, a goat infection model with Mycoplasma was established and the pathogen was tested using PCR. The results indicated that this approach could be effectively utilized for the rapid detection of mycoplasma in clinical settings. Additionally, the prevalence of contagious pleuropneumonia of sheep in Qinghai Province was further investigated through PCR analysis. A total of 340 nasal swabs were collected from 17 sheep farms in Qinghai province. Among these samples, 84 tested positive for Mycoplasma mycoides subsp. capri (Mmc) and 148 tested positive for Mycoplasma ovipneumoniae (Movi), resulting in positive rates of 24.71% and 43.53% respectively. Furthermore, our investigation revealed positive PCR results for nasal swabs, trachea, and lung samples obtained from sheep exhibiting symptoms suggestive of mycoplasma infection. Moreover, three distinct strains were isolated from these positive samples. Additionally, the inflammatory cytokines of peripheral blood mononuclear cells (PBMCs) were assessed using RT-PCR. The findings demonstrated a high susceptibility of sheep to Movi in Qinghai province, with infected sheep displaying an inflammatory response. Consequently, the outcomes of this study will furnish valuable epidemiological insights for the effective prevention and control of this disease within Qinghai Province.
Topics: Animals; Sheep; Pneumonia, Mycoplasma; Sheep Diseases; China; Mycoplasma ovipneumoniae; Goats; Prevalence; Polymerase Chain Reaction
PubMed: 38771810
DOI: 10.1371/journal.pone.0299928 -
Frontiers in Cellular and Infection... 2024() belongs to the class , characterized by a very small genome size, reduction of metabolic pathways, including transcription factors, and the absence of a cell wall....
INTRODUCTION
() belongs to the class , characterized by a very small genome size, reduction of metabolic pathways, including transcription factors, and the absence of a cell wall. Despite this, they adapt well not only to specific niches within the host organism but can also spread throughout the body, colonizing various organs and tissues. The adaptation mechanisms of , as well as their regulatory pathways, are poorly understood. It is known that, when adapting to adverse conditions, can undergo phenotypic switches that may persist for several generations.
METHODS
To investigate the adaptive properties of related to survival in the host, we conducted a comparative phenotypic and proteogenomic analysis of eight clinical isolates of obtained from patients with urogenital infections and the laboratory strain H-34.
RESULTS
We have shown that clinical isolates differ in phenotypic features from the laboratory strain, form biofilms more effectively and show resistance to ofloxacin. The comparative proteogenomic analysis revealed that, unlike the laboratory strain, the clinical isolates possess several features related to stress survival: they switch carbon metabolism, activating the energetically least advantageous pathway of nucleoside utilization, which allows slowing down cellular processes and transitioning to a starvation state; they reconfigure the repertoire of membrane proteins; they have integrative conjugative elements in their genomes, which are key mediators of horizontal gene transfer. The upregulation of the methylating subunit of the restriction-modification (RM) system type I and the additional components of RM systems found in clinical isolates suggest that DNA methylation may play a role in regulating the adaptation mechanisms of in the host organism. It has been shown that based on the proteogenomic profile, namely the genome sequence, protein content, composition of the RM systems and additional subunits HsdM, HsdS and HsdR, composition and number of transposable elements, as well as the sequence of the main variable antigen Vaa, we can divide clinical isolates into two phenotypes: typical colonies (TC), which have a high growth rate, and atypical (aTC) mini-colonies, which have a slow growth rate and exhibit properties similar to persisters.
DISCUSSION
We believe that the key mechanism of adaptation of in the host is phenotypic restructuring, leading to a slowing down cellular processes and the formation of small atypical colonies. This is due to a switch in carbon metabolism and activation the pathway of nucleoside utilization. We hypothesize that DNA methylation may play a role in regulating this switch.
Topics: Humans; Mycoplasma hominis; Proteogenomics; Mycoplasma Infections; Adaptation, Physiological; Biofilms; Genome, Bacterial; Phenotype; Anti-Bacterial Agents; Bacterial Proteins; Drug Resistance, Bacterial
PubMed: 38756231
DOI: 10.3389/fcimb.2024.1398706 -
Frontiers in Cellular and Infection... 2024Exploring the effect of SJQJD on the pulmonary microbiota of chronic obstructive pulmonary disease (COPD) rats through 16S ribosomal RNA (rRNA) sequencing.
OBJECTIVE
Exploring the effect of SJQJD on the pulmonary microbiota of chronic obstructive pulmonary disease (COPD) rats through 16S ribosomal RNA (rRNA) sequencing.
METHODS
A COPD rat model was constructed through smoking and lipopolysaccharide (LPS) stimulation, and the efficacy of SJQJD was evaluated by hematoxylin and eosin (H&E) staining and Enzyme-Linked Immunosorbnent Assay (ELISA). The alveolar lavage fluid of rats was subjected to 16S rRNA sequencing. The diversity of lung microbiota composition and community structure was analyzed and differential microbiota were screened. Additionally, machine learning algorithms were used for screening biomarkers of each group of the microbiota.
RESULTS
SJQJD could improve lung structure and inflammatory response in COPD rats. 16s rRNA sequencing analysis showed that SJQJD could significantly improve the abundance and diversity of bacterial communities in COPD rats. Through differential analysis and machine learning methods, potential microbial biomarkers were identified as , , and .
CONCLUSION
SJQJD could improve tissue morphology and local inflammatory response in COPD rats, and its effect may be related to improve pulmonary microbiota.
Topics: Pulmonary Disease, Chronic Obstructive; Animals; Microbiota; Lung; Rats; RNA, Ribosomal, 16S; Drugs, Chinese Herbal; Disease Models, Animal; Male; Bacteria; Bronchoalveolar Lavage Fluid; Rats, Sprague-Dawley
PubMed: 38746785
DOI: 10.3389/fcimb.2024.1379831