Frontiers in Cellular and Infection Microbiology最新文献

Introduction: After a prolonged lull during COVID-19 non-pharmaceutical interventions, Mycoplasma pneumoniae activity re-emerged in 2023 in multiple regions; in China this occurred against a backdrop of very high macrolide resistance. We conducted a retrospective single-center study of pediatric M. pneumoniae pneumonia in Jinan, comparing a pre-resurgence period (2021) with 2023-2024.

Methods: Clinical data were linked to whole-genome sequencing of 227 cultured isolates. We assessed lineage composition and relatedness using core-genome phylogenetics and SNP-threshold networks, and compared diversity and pan-genome functional profiles across major clades. Phenotypic antimicrobial susceptibility testing was performed.

Results: The proportion of severe cases increased from 7.4% (2021) to 19.9% (2024). Over the same interval, the P1-1/ST3 lineage rose from 41.9% to 84.0%, displacing previously co-circulating lineages. Core-genome analyses indicated reduced diversity and a compact ST3 cluster within the T1-3R subclade of the P1-type 1 lineage (EC1 clone), alongside a smaller P1-type 2/T2-2 (EC2/ST14) clade. Using a ≤11-SNP threshold, 74% of isolates fell within the largest connected component. Pan-genome comparisons suggested enrichment of replication/recombination/repair functions in T1-3R, whereas canonical adhesion factors and the CARDS toxin were conserved. All isolates carried the 23S rRNA A2063G substitution with phenotypic macrolide resistance, while in vitro susceptibility to tetracycline and levofloxacin was retained.

Discussion: The 2023-2024 resurgence coincided with clonal replacement by P1-1/ST3 in a setting of fixed macrolide resistance and an increase in severe pediatric disease. Given the retrospective, culture-based design, this should be interpreted as a temporal association rather than evidence that ST3 intrinsically caused more severe disease. These findings support consideration of non-macrolide agents in similar high-resistance settings and motivate prospective genomic-clinical surveillance.

The rise of methicillin-resistant Staphylococcus aureus (MRSA) underscores the urgent need for rapid, sensitive, and portable diagnostics. In this paper, we have critically reviewed recent advances in biosensor technologies, integrating nanomaterials, aptamers, CRISPR/Cas systems, and microfluidic lab-on-a-chip platforms, that enable sub-hour and ultrasensitive detection of S. aureus and its resistance genes. These innovations offer powerful alternatives to conventional culture and PCR assays, forming the way for real-time, point-of-care antimicrobial resistance testing. Remaining challenges include matrix interference, lack of standardization, and limited clinical validation, yet continued integration with artificial intelligence and digital systems promises transformative diagnostic capabilities.

Introduction: The parasite Schistosoma mansoni has a unique reproductive biology, because female maturation depends on constant pairing with a male. Paired females produce each up to 300 eggs per day, which are the pathogenic factors of schistosomiasis, a neglected tropical disease that affects > 240 million people worldwide. Due to the importance of egg production for life-cycle maintenance and pathology, molecular mechanisms controlling schistosome reproduction are in the focus of research. Among the candidates involved in regulating the reproductive biology of this parasite are DEAD-box RNA helicases. These enzymes are associated with various cellular processes, including ribosome biogenesis and post-transcriptional regulation. In platyhelminths, helicases are largely unexplored. One member of the DEAD-box helicase family is the eukaryotic translation initiation factor 4A (eIF4A), which unwinds stable RNA structures in the 5'-untranslated region of selected mRNAs.

Objectives: We functionally characterized two eIF4A isoforms of S. mansoni (SmeIF4A-a and SmeIF4A-b), which are potentially involved in translation initiation like their human orthologs, to evaluate their importance for parasite vitality and reproduction.

Methodologies/findings: Transcripts of both SmeIF4A isoforms were localized in female ovaries as shown by whole mount in situ hybridization. RNA-interference (RNAi) experiments revealed a decisive role of SmeIF4A-a in gonad maintenance and egg production. Stem-cell proliferation assays and confocal laser scanning microscopy uncovered the loss of proliferation activity in germinal and somatic stem cells after Smeif4a-a RNAi. No distinct function was found for SmeIF4A-b.

Conclusion: Our results suggest that SmeIF4A-a is a key factor in stem-cell proliferation and gonad maintenance, and thus also in egg production.

Introduction: Enterocytozoon bieneusi is the most prevalent microsporidian species infecting humans and causing diarrhea. Epidemiological investigations seldom focus on this pathogen, and its disease burden has been underestimated. This research investigated the prevalence and genotypic characteristics of E. bieneusi in patients with diarrhea from Guangdong (Zhuhai), Shandong (Qingdao), Shanghai and Zhejiang (Wenzhou) Provinces, China.

Methods: A total of 691 fecal specimens from patients exhibiting diarrhea were collected and subjected to polymerase chain reaction (PCR) detection, targeting the internal transcribed spacer (ITS) region of the E. bieneusi genome. Genotypes were identified by sequencing PCR products, and zoonotic risk was evaluated through homology and phylogenetic analysis.

Results: 4.9% (34/691) of patients were positive for E. bieneusi. The patients from Shanghai had the highest incidence at 14.3% (21/147), which was significantly higher than those in Qingdao (2.9%, 5/171), Wenzhou (3.3%, 3/90), and Zhuhai (1.8%, 5/283) (χ² = 35.5, P < 0.001). Meanwhile, the positive rate was 7.1% (18/254), 3.1% (10/325) and 5.4% (6/112) among children, adults, and the elderly, respectively. Additionally, the positive rate of patients in rural areas was 8.6% (26/302), significantly higher than that in urban areas, which was 2.1% (8/389) (χ² = 15.6, P < 0.001). Twelve genotypes of E. bieneusi were identified, including seven known genotypes: CHG3 (n = 17), CHG19 (n = 3), EbPigITS7 (n = 3), Type IV (n = 3), CHG5 (n = 1), EbpA (n = 1), and S7 (n = 1), as well as five novel genotypes (SHH1, WZH1, ZHH1, ZHH2 and ZHH3), each represented by a single sample. The identified genotypes can be categorized into Groups 1, 2, 12, and 13 through phylogenetic analysis.

Conclusions: This study offers insights into the epidemiology and genetic diversity of E. bieneusi among patients experiencing diarrhea in four provinces of China. It also underscores the necessity of ongoing monitoring and management to prevent the spread of this pathogen.

Introduction: The diminishing efficacy of conventional antibiotics against methicillin-resistant Staphylococcus aureus (MRSA) necessitates novel therapeutic strategies. Drug repurposing represents a promising approach. This study investigates the antibacterial potential of Nifuratel, a repurposed agent, against MRSA.

Methods: In vitro antibacterial activity was assessed against type strains and clinical isolates via minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. The propensity for resistance development was evaluated. Sub-MIC effects on key virulence phenotypes-biofilm formation, hemolysis, auto-aggregation, and surface spreading-were examined. The mechanism of action was investigated using transmission electron microscopy, fluorescence probes, and molecular dynamics simulations. Efficacy and biocompatibility were evaluated in vivo using murine abscess and wound infection models, with assessments of bacterial load, inflammation, wound healing, hemolysis, and organ toxicity.

Results: Nifuratel exhibited potent bactericidal activity with MICs of 2-8 µg/mL and MBCs of 8-16 µg/mL, and a low propensity for resistance development. At sub-MIC concentrations, it significantly suppressed MRSA virulence phenotypes. Mechanistic studies revealed that Nifuratel disrupts the proton motive force by dissipating both the transmembrane potential and proton gradient, without causing direct membrane damage. In vivo, Nifuratel treatment significantly reduced bacterial loads, attenuated inflammation, and promoted wound healing comparably to fusidic acid. The compound demonstrated excellent biocompatibility with minimal hemolysis and no observed organ toxicity.

Discussion: These results identify Nifuratel as a promising repurposed antimicrobial agent against MRSA. Its dual capability to exert direct bactericidal activity by disrupting PMF and attenuate key virulence factors, combined with a favorable resistance profile and biocompatibility in vivo, supports its potential for further therapeutic development.

Background: Previous studies have demonstrated that carvacrol (Car) ameliorates vascular and hepatic injury in db/db mice, but its low bioavailability limits clinical translation.

Methods: To address this, this study constructed carvacrol-loaded polymeric nanoparticles (Car@PLGA-NPs) to enhance carvacrol bioavailability and fully explore its novel mechanisms of action on islet function and gut homeostasis in a diabetic model. We used C57BL/6J db/db mice to measure serum fasting blood glucose, oral glucose tolerance (OGTT), insulin tolerance (ITT), and lipid profiles. Fecal samples were collected for 16S rRNA sequencing to analyze gut microbiota composition and its correlation with host indices. Pancreatic and intestinal tissues underwent histopathological staining, immunofluorescence, and Western blotting to detect endoplasmic reticulum (ER) stress-related protein expression levels (p-IRE1α, XBP1S, PERK, p-ElF2α).

Results: Results demonstrated that Car@PLGA-NPs, compared to free carvacrol, significantly improved insulin sensitivity, reduced fasting blood glucose, ameliorated dyslipidemia, attenuated inflammation, and mitigated oxidative stress in db/db mice. 16S rRNA sequencing revealed that Car@PLGA-NPs remodeled the gut microbiota composition, with Alloprevotella abundance showing a negative correlation with colonic ER stress proteins (p-IRE1α and p-ElF2α). Immunofluorescence and Western blotting further confirmed that Car@PLGA-NPs significantly suppressed the expression of ER stress-related proteins (p-IRE1α, XBP1S, PERK, p-ElF2α) in both islet and colonic tissues, demonstrating superior efficacy to free carvacrol.

Conclusions: Collectively, this study confirms that the PLGA nanocarrier effectively enhances carvacrol bioavailability. Car@PLGA-NPs improve islet function and intestinal homeostasis in diabetic mice by remodeling the gut microbiota and subsequently inhibiting ER stress in pancreatic and intestinal tissues, providing a novel nano-drug delivery system and a "microbiota-ER stress" regulatory axis for diabetes treatment.

Background: Fusobacterium nucleatum is an oncobacterium capable of promoting the growth and chemotherapy resistance of colonised tumours. Although F. nucleatum is usually susceptible to a range of antibiotics in vitro, these have been associated with worse outcomes when administered with anti-neoplastic chemotherapy. Bacteriophages are viewed as natural alternatives to antibiotics that provide bacterial-specific targeting.

Methods: In this study, we have employed an F. nucleatum specific bacteriophage, FNU1, to limit the effects of this oncobacteria in colon cancer and gastric cancer cell models.

Results: We demonstrated that FNU1 was able to negate the F. nucleatum induced growth stimulatory effects, migratory ability, autophagy, anti-apoptotic effects and chemotherapy resistance in these cell models.

Conclusion: Treatments with bacteriophage FNU1, therefore, have the potential to augment existing cancer therapy, and further testing in animal models is warranted.

Liver fibrosis and cirrhosis are common outcomes of chronic liver diseases such as viral hepatitis, alcoholic liver disease, and non-alcoholic fatty liver disease. Despite diverse causes, they share core pathological features including hepatic stellate cell activation, extracellular matrix deposition, immune dysregulation, and metabolic alterations. Recent advances in multi-omics technologies-encompassing transcriptomics, proteomics, and metabolomics-enhance our understanding of the molecular and cellular mechanisms driving liver fibrosis. This review integrates findings from human studies and animal models, highlighting key pathological pathways and their interactions. Multi-omics analyses also clarify therapeutic mechanisms targeting oxidative stress, inflammation, and metabolic dysfunction. Cross-species comparisons confirm the translational relevance of animal models and underscore the value of multi-omics approaches in biomarker discovery and precision therapy development. Overall, these insights provide a systems-level understanding of liver fibrosis, facilitating advances in diagnosis and treatment strategies.

Background: Periodontal disease and atherosclerosis are two highly prevalent chronic inflammatory conditions that may be pathophysiologically linked.

Objective: This review aims to critically assess the current literature regarding the potential causal relationship between periodontitis, the atherosclerotic process, and particularly the progression of carotid artery disease. Although numerous observational studies support an association between periodontitis and cardiovascular diseases, the evidence remains inconclusive in demonstrating periodontal disease as an independent risk factor in the development of carotid atherosclerotic plaques.

Conclusion: While there is substantial biological plausibility for a link between periodontal disease and atherosclerosis, current evidence is insufficient to confirm a direct causal role, particularly in carotid artery disease. Further longitudinal and interventional studies are necessary to elucidate the mechanisms involved and determine whether periodontal treatment may contribute to cardiovascular risk reduction. The potential public health implications of these findings highlight the necessity for comprehensive preventive and therapeutic oral health interventions aimed at reducing associated systemic risks.

Carbapenem-resistant Enterobacteriaceae (CRE) pose a significant threat in urinary tract infections (UTIs), which are among the most common infectious diseases. This review summarizes the risk factors and treatment advances for CRE-associated UTIs. Key risk factors include advanced age, history of carbapenem use, invasive urological procedures, indwelling catheters, immunosuppression (e.g., in transplant recipients), and prolonged hospitalization. The prognosis of CRE UTIs is generally better than infections at other sites but is influenced by factors like ICU admission and treatment failure. Treatment relies heavily on novel antibiotics, such as ceftazidime-avibactam and the siderophore cephalosporin cefiderocol, often used in combination regimens to enhance efficacy and prevent resistance. Recent clinical trials have demonstrated the effectiveness and safety of cefiderocol against CRE UTIs. Research on adjuvants like metal ion chelators (e.g., copper, bismuth) to restore antibiotic susceptibility is promising. Future efforts should focus on developing new antimicrobials, establishing rapid diagnostics for precise control, and conducting large-scale studies to optimize individual treatment strategies and infection control measures to improve patient outcomes and curb CRE spread.