Frontiers in Cellular and Infection Microbiology最新文献

Porcine epidemic diarrhea virus (PEDV) is a highly contagious virus that causes severe diarrhea and high mortality in neonatal piglets. Current control measures, such as inactivated and live-attenuated vaccines, have limitations in providing complete protection. In this study, we evaluate the immunogenicity and protective efficacy of a PEDV S protein subunit vaccine compared to a traditional inactivated vaccine. Piglets and Sows were immunized with either the subunit vaccine or an inactivated vaccine, and serum samples were collected to assess IgG and neutralizing antibody levels. Results demonstrated that the S protein subunit vaccine induced significantly higher IgG and neutralizing antibody levels in both piglets and sows compared to the inactivated vaccine. Piglets born to immunized sows were challenged with a virulent PEDV strain. Piglets from the subunit vaccine group exhibited lower viral shedding, reduced clinical symptoms, and minimal intestinal lesions. These findings suggest that the PEDV S protein subunit vaccine provides enhanced immunity and protection against PEDV, making it a promising candidate for preventing PEDV infections in swine.

The PhoP response regulator and the cognate sensor kinase PhoQ form one of the two-component signal transduction systems that is highly conserved in bacteria. The PhoP/PhoQ system is a crucial mediator of signal transduction. It regulates the expression of bacterial environmental tolerance genes, virulence factors, adhesion, and invasion-related genes by sensing various environmental signals in the host, including Mg²⁺, low pH, antimicrobial peptides, and osmotic pressure. In this review, we describe the PhoP/PhoQ system-induced signal composition and its feedback mechanism, and the abundance of PhoP phosphorylation in the activated state directly or indirectly controls the transcription and expression of related genes, regulating bacterial stability. Then, we discuss the relationship between the PhoP/PhoQ system and other components of the TCS system. Under the same induction conditions, their interaction relationship determines whether bacteria can quickly restore their homeostasis and exert virulence effects. Finally, we investigate the coordinated role of the PhoP/PhoQ system in acquiring pathogenic virulence.

Background: The COVID-19 pandemic has led to the excessive use of antimicrobials in critically ill patients. Infections caused by Acinetobacter baumannii have increased significantly both regionally and globally during the COVID-19 pandemic, posing dramatic challenges for intensive care unit (ICU) patients. This study aimed to determine the prevalence, antimicrobial resistance patterns, presence of selected antimicrobial resistance genes, and genetic diversity of A. baumannii isolates obtained from COVID-19 cases admitted to the ICU at the University Hospital in Iran.

Materials and methods: This was a cross-sectional and single-center study comprising patients with A. baumannii infections admitted to the ICU with COVID-19 between April and November 2021. The demographic and clinical data of the patients were collected. Antimicrobial susceptibility testing was conducted based on Clinical Laboratory Standards Institute guidelines. This study used PCR and multiplex PCR to investigate antibiotic resistance genes (ARGs) and global clones (GC), respectively. Genetic diversity was investigated by repetitive element sequence-based PCR (REP-PCR).

Results: The prevalence of A. baumannii coinfection in COVID-19 cases was 8.1% (43/528). More than 90% (39/43) of A. baumannii isolates were resistant to cefepime, ampicillin-sulbactam, gentamicin, trimethoprim-sulfamethoxazole and amikacin. Furthermore, 44.2% (19/43) of isolates were resistant to colistin. There were 91% (39/43) isolates that were extensively drug-resistant (XDR). The most prevalence carbapenem resistance encoding genes were bla _-OXA-23 65.1% (29/43) and bla _NDM 41.8% (18/43). The most common aminoglycoside resistance genes were aac(6')-Ib 65.1% (28/43) and ant(2)-Ia 46.5% (20/43). Isolates from the prominent Global clone GCII comprised 83.7% (36/43) of total isolates. Genetic fingerprinting using REP-PCR revealed that 39 typeable A. baumannii isolates were categorized into 12 distinct genotypes, of which 72% (28/39) of isolates belonged to one genotype.

Conclusion: The high prevalence of XDR A. baumannii such as carbapenem and colistin-resistant strains, poses a significant concern for the treatment of COVID-19 patients, heightening the risk of therapeutic failure. The data demonstrate the dissemination of a single A. baumannii clone carrying multiple ARGs within our hospital. Regarding the limited therapeutic options, it is crucial to implement effective prevention and containment policies to curb the spread of these strains.

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) exhibits diverse genotypes with varying virulence and resistance profiles, particularly in the context of bloodstream infections (BSI). This study investigates the prevalence of the sasX, mupA, and qacA/B genes among MRSA isolates from bloodstream infections in southern China and analyzes their genetic relatedness.

Methods: A polymerase chain reaction (PCR) assay was developed to detect the presence of the sasX gene, which is associated with nasal colonization, immune evasion, and virulence, the mupirocin resistance gene mupA, and the chlorhexidine tolerance gene qacA/B in a total of 77 MRSA isolates. Multilocus sequence typing (MLST) was performed to determine the sequence types (STs) and assess the genetic relatedness of the isolates. The resistance of these strains to 16 antibiotics was also analyzed. The distribution of these genes and their association with epidemic STs were analyzed.

Results: A total of 26 STs were identified, with notable prevalence in five epidemic clones: ST59, ST5, and ST764. The prevalence of the sasX, mupA, and qacA/B genes across all isolates was 23.4%, 33.8%, and 79.2%, respectively. Specifically, the frequency of the sasX gene was highest in ST59 (29.4%), ST239 (100%), and ST764 (37.5%); mupA was most prevalent in ST5 (66.7%), ST59 (17.6%), ST764 (37.5%), and ST15 (100%); qacA/B was predominantly found in ST59 (88.2%), ST5 (66.7%), ST398 (85.7%), ST764 (50.0%), and ST239 (100%). The gene distribution patterns revealed that sasX+ qacA/B+ mupA+ strains were closely associated with epidemic clones ST6290 and ST88, whereas sasX+ qacA/B+ mupA- strains were linked to ST59, ST239, and ST764.

Discussion: Notably, forty-seven (61%) MRSA BSI strains were multidrug-resistant, with the majority exhibiting resistance to penicillin, erythromycin, and clindamycin. Major MRSA clones in southern China include ST59, ST5, ST764, and ST398. In this study, sasX, mupA and qacA/B genes were present in the MRSA isolates, with the mupA gene being the most prevalent. Variations in the prevalence of virulence and resistance genes among these epidemic strains underscore the need for targeted infection control measures. These findings contribute to a better understanding of the genetic epidemiology of MRSA in the region, facilitating the development of effective prevention and control strategies for BSI.

Introduction: Bloodstream infections are a critical challenge worldwide due to the slow turnaround time of conventional microbiological tests for detecting bacteremia in septic patients. Noscendo GmbH (Duisburg, Germany) has developed the CE/IVD pipeline DISQVER for clinical metagenomics testing based on cell-free DNA (cfDNA) from blood samples to address this issue.

Methods: We conducted a retrospective study to evaluate the diagnostic utility of this methodological setup in improving treatment decisions since it was introduced into our clinical setting. Between January 2021 and June 2022, the first 300 cases in which DISQVER was applied at our university hospital were collected and analyzed. The results were compared with routine microbiology test results, clinical picture, associated treatment decisions, and clinical course.

Results: Our findings demonstrate that DISQVER results where no pathogen was reported effectively ruled out bacterial bloodstream infections, whereas positive results varied in their usefulness. While the metagenomic approach proved highly valuable for detecting non-culturable and rare pathogens, its utility was limited in cases where detected microorganisms were commonly associated with the microbiota.

Discussion: Performing on-site analysis might mitigate delays resulting from logistical challenges and might help optimizing antibiotic stewardship. Once prompt results can be obtained, the relevance of incorporating molecular resistograms will become more pronounced. Further, the specific patient subgroups that most benefit from this analysis must be worked out. Guiding clinicians in identifying the infection focus based on the detected bacteria would significantly improve patient care. Lastly, evidence of filamentous fungi must be diligently followed up.

The risk of children being infected with Influenza A virus (IAV) is high, and if not treated promptly, it can lead to serious illness. Compared with control group, IAV infection decreased the contents of platelet, white blood cell, lymphocyte, eosinophil, basophil, CD3⁺ T cells, CD4⁺ T cells, CD8⁺ T cells, and B cells, while increasing the number of red blood cell. Additionally, IAV infection increased serum concentrations of total protein, albumin and lipase, while decreasing the contents of calcium, triglyceride, total bilirubin, direct bilirubin, indirect bilirubin and gamma-glutamyltransferase. However, the interactions between the respiratory microbiome and metabolites and their impact on IAV in children remains unclear. Ultra performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-QTOF/MS) and 16S rRNA gene sequencing were employed to analysis the respiratory microbiome and serum metabolic characteristics of 85 patients with IAV infection and age-matched 55 controls with respiratory disease who tested negative for 13 types of respiratory pathogens. The serum metabolic profile of IAV patients was significantly changed, and the purine metabolism was destroyed. Purine metabolism was also enriched in H3N2 patients compared to H1N1, with increased xanthine, deoxyguanosine, and inosine. The respiratory microbiome structure in children with IAV, including H1N1 and H3N2, was significantly different from that of the control, with significantly increased Chao index. The Mantel test revealed the correlation and consistency in the trends of Haemophilus, Ureaplasma and Inosine. This study revealed the characteristics of the respiratory microbiome and serum metabolites in pediatric patients with IAV, providing a new direction for exploring the pathogenesis of IAV in children.

Introduction: Endometrial cancer (EC) is a significant gynecological malignancy with increasing incidence worldwide. Emerging evidence highlights the role of the uterine microbiome in the pathogenesis of EC. This study aims to characterize the uterine microbiome in EC patients and identify potential microbial biomarkers, with a focus on Anaerococcus as a differentiating taxon.

Methods: The endocervical canal swabs from patients with EC (n=16) and non-cancerous patients (EM, n=13) were collected. The V3-V4 region of the 16S rRNA gene was sequenced using the Illumina platform. Bioinformatic analyses were performed with QIIME2, and statistical comparisons were conducted to assess differences in microbial composition and diversity. In vitro experiments were conducted to assess the functional impact of Anaerococcus on human uterine fibroblasts, including its ability to adhere to the human cells and induce oxidative stress.

Results: The α-diversity metrics, including Shannon entropy and observed amplicon sequence variants (ASVs), revealed significantly higher microbial diversity in EC samples compared to EM. Anaerococcus was identified as a key taxon differentiating EC from EM groups, showing a higher relative abundance in EC samples. Functional predictions and in vitro assays indicated that Anaerococcus may contribute to carcinogenesis by inducing reactive oxygen species (ROS) production, and has the high ability to adhere to the human endometrial fibroblasts.

Discussion: The study provides evidence of distinct microbial signatures in EC, with Anaerococcus emerging as a potential biomarker. The in vitro findings suggest its role in endometrial carcinogenesis, underscoring its potential as a target for future diagnostic and therapeutic applications.

The COVID-19 pandemic highlighted the critical role of viral genomic surveillance, prompting numerous countries to enhance their monitoring systems for acute respiratory infections (ARIs), especially influenza-like illnesses (ILIs). Given the significance of asymptomatic cases in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, cases often undetected by the ILI surveillance, a more comprehensive approach was essential to track the circulation of SARS-CoV-2 variants in the population. In response, many countries swiftly adopted wastewater surveillance, which allowed the early detection of SARS-CoV-2 variants before they were identified through molecular characterization from confirmed clinical cases. In this report, we detail the implementation of SARS-CoV-2 wastewater genomic surveillance in Panama during the first half of 2024. Wastewater samples were collected monthly in duplicate at two collection points from three districts of Panama city metropolitan area for testing by SARS-CoV-2 RT-qPCR, and positive samples were analyzed by next-generation sequencing to identify sublineages. A total of 36 wastewater samples and 822 samples obtained through the clinical surveillance were analyzed for molecular detection and sequencing. Sublineages detected by wastewater surveillance were compared to those detected by clinical surveillance for the same period of time. Wastewater surveillance allowed the identification of the Omicron sublineage JN.1.16.1 in the capital city and its surroundings, which was not detected by the clinical surveillance in the country, despite its global circulation. This highlights the critical need to sustain both genomic surveillance programs beyond the pandemic in countries like Panama that serve as pivotal exchange hubs.

Harnessing the immunomodulatory potential of bacterial metabolites opens up exciting possibilities for treating various immune-related disorders. However, turning this potential into a reality presents significant challenges. This review investigates these challenges, focusing on discovery, production, characterization, stability, formulation, safety, and individual variability limitations. The limited bioavailability of many metabolites, as well as potential improvements along with the potential for off-target effects and the importance of precise targeting, are emphasized. Furthermore, the complex interactions between gut bacterial metabolites and the microbiome are investigated, highlighting the importance of personalized approaches. We conclude by discussing promising advances in metagenomics, metabolomics, synthetic biology, and targeted delivery systems, which hold out hope for overcoming these limitations and paving the way for the clinical translation of bacterial metabolites as effective immunomodulators.