Frontiers in Cellular and Infection Microbiology最新文献

Objectives: The growing burden of drug-resistant tuberculosis (TB) constitutes a major public health challenge. Ethionamide (ETH), a second-line anti-TB drug, plays an important role in the treatment of multidrug-resistant tuberculosis (MDR-TB). However, the molecular mechanisms underlying ETH resistance remain incompletely elucidated. Thus, this study aimed to evaluate the effects of mutations in ETH resistance-associated genes (inhA, ethA, ethR, and mshA) on ETH resistance levels among Mycobacterium tuberculosis (MTB) isolates from China.

Methods: A total of 137 MTB isolates from China were tested for ETH minimum inhibitory concentrations (MICs) pusing Sensititre^® plates, and the sequences of four ETH resistance-associated genes were analyzed based on genomic and PCR sequencing data.

Results: Our results showed that 95.1% (39/41 isolates) of ETH-resistant isolates harbored at least one mutation in these four ETH resistance-associated genes. Most mutations were found in the inhA and ethA (including 5' untranslated region). Mutations in inhA region were mainly concentrated at the -777C>T site, whereas those in the ethA region were relatively scattered. Notably, multiple mutations were common in high-level ETH-resistant strains and were significantly associated with high-level resistance (P = 0.012). Furthermore, several novel single mutations in ETH-resistant strains, including inhA -100C>A, ethA -31G>A, and mshA Tyr155Ser, were detected.

Conclusion: Different individual mutations and multiple concurrent mutations in ETH resistance-associated genes are associated with varying levels of ETH resistance. These results broaden our understanding of the molecular characteristics of ETH resistance in China.

Background: Severe community-acquired pneumonia (SCAP) remains a major cause of mortality in the paediatric population, with current diagnostic and treatment approaches often proving insufficient and contributing to the growing challenge of antibiotic resistance. This study explored the potential of metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid as a tool to enhance the precision of antibiotic management in children with SCAP.

Methods: A retrospective cohort study of 202 paediatric patients with community-acquired pneumonia (aged 1 month-18 years) admitted to the First Affiliated Hospital of Xinxiang Medical University (November 2020-March 2023) was conducted. Patients were grouped by severity (intensive care unit [ICU]/non-ICU) and mNGS timing (early: ≤72 hours post-admission; late: >72 hours). The diagnostic efficacy of mNGS versus conventional microbiological techniques (CMT) was evaluated using sensitivity, specificity, positive/negative predictive values and area under the receiver operating characteristic curve (AUC) analysis. Antibiotic adjustments and clinical outcomes were analysed via survival statistics.

Results: Metagenomic next-generation sequencing showed a higher positive detection rate (98.51%) than CMT (47.52%) (AUC = 0.82, 95%CI: 0.76-0.88). Of the 202 patients, 127 (62.87%) were male, with a median age of 1.88 years (interquartile range: 0.29-7 years). Early mNGS was associated with fewer extrapulmonary complications (69.63% vs 55.22% in the late group, p < 0.05), and shorter hospitalisation (median 13 vs 15 days, p <0.01). Antibiotic escalation occurred in 50 (24.75%) cases, de-escalation in 22 (10.89%) and same-level adjustment in 25 (12.38%).

Conclusion: Metagenomic next-generation sequencing outperforms CMT in pathogen detection. Early mNGS is associated with improved clinical outcomes, suggesting its potential utility in paediatric SCAP management.

Akabane virus (AKAV), an arthropod-borne pathogen causing severe reproductive failure in ruminants, poses a major threat to livestock industry. Given the lack of vaccines and antiviral drugs against AKAV, the development of rapid antiviral screening tools is urgently needed. To establish a quantifiable platform for AKAV research, we constructed a reporter virus (rAKAV-L-HiBiT) by inserting the 11-amino-acid HiBiT subunit of NanoLuc luciferase into the C-terminus of the L protein. The recombinant virus was characterized for growth kinetics, genetic stability, and luciferase activity. rAKAV-L-HiBiT exhibited a similar replication profile to wild-type AKAV and maintained stable luciferase activity over 10 passages in vitro. Crucially, luciferase activity of rAKAV-L-HiBiT showed a strong positive correlation with viral loads (r > 0.99), validating its utility as a convenient and rapid platform for AKAV quantification. Subsequently, we applied this platform to neutralization and antiviral compound screening assays and Remdesivir was identified as a potent inhibitor of AKAV. Taken together, our study presents rAKAV-L-HiBiT as a reliable tool for rapid antiviral drug discovery and neutralization testing.

Background: Chronic hepatitis B (CHB) remains a global health challenge, with current therapies achieving low rates of functional cure (FC). Reliable biomarkers are urgently needed to guide individualized treatment. This study characterized the immune-metabolic profiles of CHB patients receiving pegylated interferon-α (PegIFN-α) or nucleos(t)ide analogues (NAs), focusing on mitochondrial function as a novel predictor of therapeutic response.

Methods: A total of 93 CHB patients and 32 healthy controls were recruited from three centers. Peripheral blood leukocyte subsets and mitochondrial parameters, including mitochondrial mass (MM) and the percentage of cells with low mitochondrial membrane potential (MMPlow%), were assessed by flow cytometry. Multivariate logistic regression and receiver operating characteristic (ROC) analyses were used to identify independent predictors and evaluate biomarker performance for FC.

Results: Untreated CHB patients showed marked mitochondrial depletion across immune subsets. NA therapy normalized mitochondrial parameters without improving FC rates, whereas PegIFN-α therapy selectively remodeled CD4+ T cell metabolism and promoted monocyte differentiation. Improved mitochondrial efficiency in CD8+ T cells and elevated monocyte counts were closely associated with HBsAg clearance. Lymphocyte MMPlow% showed the strongest individual predictive value, while an integrated immune-metabolic model further enhanced accuracy for FC prediction.

Conclusion: Immune-metabolic remodeling underlies PegIFN-α-induced functional cure in CHB. Mitochondrial profiling provides a promising framework for precision stratification and immune-based therapeutic optimization.

Background: Corynebacterium parakroppenstedtii, and C. pseudokroppenstedtii are emerging as significant pathogens in mastitis. Despite its clinical significance, data on its epidemiological, microbiological, and clinical features remain limited.

Methods: We conducted a comprehensive study on mastitis cases associated with Corynebacterium kroppenstedtii complex (CKC) in Guangdong, China (September 2021-September 2023). A total of 101 bacterial isolates were collected and initially identified as CKC using MALDI-TOF MS. Species-level confirmation was achieved through partial sequencing of the 16S rRNA, ropB, and fusA genes. Unclassified isolates were further characterized by whole genome sequencing (WGS). Clinical information was collected, and antimicrobial susceptibility testing was performed.

Results: Among the 101cases, C. parakroppenstedtii accounted for 86% of infections, while C. pseudokroppenstedtii for 12%, and a potential novel species for the remaining 2%. Notably, no C. kroppenstedtii infections were detected. Granulomatous lobular mastitis (GLM) was the predominant presentation, occurring in 72% of all cases. Comparative analysis revealed that C. pseudokroppenstedtii infections were associated with higher rates of pus formation and recurrence, whereas C. parakroppenstedtii infections were more prevalent among parous women. Moreover, C. pseudokroppenstedtii exhibited higher resistance rates to ceftriaxone (32.15% vs. 20.00%) and ciprofloxacin (75.00% vs. 19.09%) compared with C. parakroppenstedtii.

Conclusions: These findings challenge the prevailing understanding that C. kroppenstedtii is the main pathogen in mastitis and underscore the need for species-level identification to guide diagnosis and optimize antibiotic therapy for CKC-related mastitis. These insights are vital for improving clinical management and informing treatment strategies.

Background: The etiology and pathogenesis of idiopathic oligoasthenospermia (IOA) remain unclear, and current treatment options yield suboptimal outcomes. Consequently, there is an urgent need to identify novel biomarkers and develop diagnostic tools to improve patient identification and clinical management. Multi-omics technologies offer a promising pathway toward achieving this goal in the future.

Methods: This study included 40 untreated patients with idiopathic oligoasthenospermia (IOA) and 30 healthy fertile males (HP) as controls. Semen samples were analyzed using 16S rRNA gene sequencing (microbiome) and non-targeted metabolomics (GC-MS/LC-MS coupled). A microbe-metabolite association network was integrated at the genus level based on Spearman correlation algorithms.

Results: Semen microbiome analysis revealed that both microbial composition and species richness differed between IOA patients and HP controls. Non-targeted metabolomics further demonstrated characteristic metabolic dysregulation in seminal plasma of IOA patients, with a metabolic signature effectively distinguishing cases from controls (VIP > 1, FDR < 0.05). KEGG pathway enrichment analysis indicated that differentially expressed metabolites primarily involved amino acid metabolism, carbohydrate metabolism, and related signaling pathways (corrected p-value < 0.05). Construction of a Spearman correlation network between microbiota and metabolites (|r| > 0.6) identified significant interactions between core bacterial genera such as Dialister, Prevotellaceae_NK3B31_group, Lawsonella, and Blautia with seminal plasma metabolites, suggesting potential involvement of the microbiota-metabolite axis in the pathological process of IOA.

Conclusion: The microbial community structure and metabolic profiles in the semen of IOA patients exhibit significant disruption. Diagnostic models constructed based on combined microbial-metabolite features demonstrate potential for effectively distinguishing disease phenotypes. The core dysregulated bacterial genera, associated metabolites, and related pathways may serve as early diagnostic biomarkers and therapeutic intervention targets.

Hepatitis B (HB) remains a global public health challenge, imposing significant burdens on patients and society. Therapeutic strategies and novel drug development for HB continue to be a major research focus, yet current treatments fail to achieve satisfactory clinical cure rates. To address this critical gap, more effective therapeutic approaches are urgently needed. A comprehensive understanding of the hepatitis B virus (HBV) life cycle and the immunopathogenesis of persistent HBV infection, combined with innovations in drug development and delivery systems, will lead to novel strategies for treating chronic HBV infection. This review summarizes recent advances in HBV therapeutic targets, encompassing both viral life cycle and host-directed targets. We critically evaluate emerging therapeutics, including synthetic compounds, herbal medicines, and immunomodulators, along with their supporting preclinical and clinical evidence, as well as progress in drug delivery systems including liver-targeted nanoparticles, and synergistic therapeutic strategies that combine conventional and Chinese-Western medical approaches for enhanced efficacy. Through this comprehensive analysis, this review aims to provide valuable insights for clinical management of HBV and development of innovative therapies, thereby advancing the HBV treatment field. We anticipate achieving complete cure for HB in the foreseeable future.

Background: Heart failure (HF) is a primary cause of death in patients on maintenance hemodialysis (MHD), yet the role of microbial dysbiosis is poorly defined. This study characterized the salivary and gut microbiomes of MHD patients with heart failure with preserved ejection fraction (HFpEF), those without HF (NHF), and healthy controls (CON).

Methods: In this cross-sectional study (n=88), we compared the salivary and fecal microbiomes of HFpEF (n=30), NHF (n=30), and CON (n=28) groups using 16S rRNA gene sequencing. Microbial community structure and composition were analyzed.

Results: Alpha diversity and Beta diversity analysis revealed a distinct salivary microbial structure, which effectively distinguished the MHD group from the Con group (P < 0.05). Conversely, the overall gut community structure showed no significant separation. At the genus level, both MHD groups showed depletion of salivary Veillonella and gut Faecalibacterium compared to controls. Notably, LEfSe analysis highlighted salivary Anaerocolumna as a promising candidate feature associated with the HFpEF group.

Conclusion: Our analyses suggest that HFpEF in MHD patients may be associated with structural alterations in the oral microbiome, which appear more pronounced than those in the gut. Specific oral microbial signatures, particularly the enrichment of Anaerocolumna, showed associations with the HFpEF cohort in our study. This preliminary evidence positions the oral microbiome as an area worthy of further investigation for its potential role in this high-risk population.