Frontiers in Cellular and Infection Microbiology最新文献

Antimicrobial resistance (AMR) is a critical global health threat that may cause up to 10 million deaths annually by 2050, requiring integrated actions within the One Health framework. The misuse of antimicrobials across human, animal, and environmental sectors has intensified the spread of multidrug-resistant bacteria, including Escherichia coli, Staphylococcus aureus, and Klebsiella pneumoniae. In this context, Lactobacillus-derived postbiotics have emerged as eco-friendly alternatives with antimicrobial and antibiofilm properties. A systematic review was conducted to consolidate scientific evidence on the strategic potential of Lactobacillus cell-free supernatants, with a specific focus on Limosilactobacillus fermentum. Studies published between 2000 and July 2025 were screened, prioritizing investigations that evaluated antimicrobial activity, biofilm inhibition, and efficacy in biological and technological models against multidrug-resistant pathogens. After screening, 95 studies were included in the analysis. L. fermentum was deliberately selected as the focus species based on consistent evidence of postbiotic efficacy against pathogenic bacteria and biofilm formation. The reviewed studies also demonstrated favorable physicochemical stability of L. fermentum cell-free derivatives, supporting their safety and scalability for applied use. This review highlights L. fermentum as a strategic model within One Health aligned approaches to combat AMR. The findings reinforce the role of postbiotics as sustainable, effective, and scalable tools for mitigating antimicrobial resistance across human, animal, and environmental interfaces.

Background: Early assessment of acute pancreatitis (AP) severity is critical. We therefore built a web-based calculator that instantly estimates the probability that a patient admitted with AP will progress to the severe form.

Methods: Clinical records for patients who were diagnosed as AP at the Second Affiliated Hospital of Guilin Medical University between the start of 2016 and May 2025 were retrospectively examined. The dataset was randomly divided into training set (70%) and test set (30%). For the traditional machine learning models, we employed 5-fold cross-validation combined with random search for hyperparameter optimization during training. Feature selection was performed using Random Forest (RF) and the Least Absolute Shrinkage and Selection Operator (LASSO) methods. Model construction included Logistic Regression (LR), Decision Tree (DT), Naive Bayes (NB), Support Vector Machine (SVM), Multi-Layer Perceptron (MLP), Light Gradient Boosting Machine (LightGBM), Extreme Gradient Boosting (XGBoost), Artificial Neural Network (ANN), Convolutional Neural Network (CNN), and Long Short-Term Memory Network (LSTM). The area under the receiver operating characteristic curve (AUC), among other metrics, served to evaluate model efficacy. SHapley Additive exPlanations (SHAP) and Partial Dependency Plots (PDP) were employed to explain model predictions, and a clinical application risk prediction platform was further developed.

Results: 1289 patients with AP were included, with 11 variables screened to develop 10 models. Among these, the LightGBM demonstrated the highest predictive accuracy on training and test sets, with AUC (95% CI) values of 0.9726 (0.9626-0.9818) and 0.9301 (0.9113-0.9481), respectively. SHAP and PDP analyses identified Ca, WBC, α-HBDH, and Glu as key predictive features for severe acute pancreatitis (SAP). Calcium levels exerted a negative influence on SAP prediction, whereas WBC, α-HBDH, and Glu exerted positive influences, exhibiting positive synergistic effects among these three variables.

Conclusion: Our study highlights the substantial predictive potential of Ca, WBC, α-HBDH, and Glu for SAP. We have built a predictive online platform for clinical use, enabling healthcare professionals to rapidly and effectively assess SAP risk, thereby facilitating timely intervention and treatment.

Objective: To analyze the clinical differences between pertussis and/or Mycoplasma pneumoniae (MP) infections in children and provide insights for clinical differential diagnosis.

Methods: We retrospectively reviewed children with respiratory symptoms who attended Shandong University Children's Hospital (Jinan, China) from 2019 to 2024 and underwent simultaneous testing for pertussis and MP. Patients were categorized as pertussis-only, MP-only, or dual-positive, and differences in demographics, seasonality, manifestations, hematologic indices, and co-detected pathogens were analyzed.

Results: A total of 7184 children were included: 2,982 pertussis-only, 3,166 MP-only, and 1,036 dual-positive. Significant differences were observed in sex (χ² = 30.964), age (χ² = 393.010), and season (χ² = 436.070) (all p < 0.001). Pertussis-only cases were more common in boys, during spring and winter, and in patients aged 6 years to <12 years. MP-only cases clustered in ages 2 to <6 and 6 to <12 years, with peaks in summer and autumn. Dual-positive cases were slightly more frequent in girls, clustered in the 6 to <12-year-old group, and occurred more often in spring and summer. Fever (χ² = 442.36, p < 0.001) was more frequent in the MP-only and dual-positive groups, whereas gastrointestinal symptoms (χ² = 30.00, p < 0.001), cyanosis (χ² = 12.91, p = 0.002), spasmodic cough (χ² = 212.07, p < 0.001), and cockcrow-like echo (χ² = 77.38, p < 0.001) were more common in the pertussis-only group. Lung crackles (χ² = 52.44, p < 0.001) and multilobar involvement (χ² = 28.08, p < 0.001) were predominantly observed in the MP-only group. The duration of cough before diagnosis was shorter in the MP-only group than in both the pertussis-only and dual-positive groups (H = 371.49, p < 0.001). Lymphocyte counts (H = 178.03) were the highest in the pertussis-only group, and neutrophil counts (H = 119.45) and C-reactive protein (H = 369.80) were the highest in the MP-only group (all p<0.001). Among the 7184 children, 1,224 (15.65%) had codetection of other pathogens, with human rhinovirus, Haemophilus influenzae, and Streptococcus pneumoniae most common. The MP-only group was more often accompanied with influenza A/B (χ² = 16.688, p < 0.001) and Legionella pneumophila (χ² = 12.715, p = 0.002); pertussis-only, Streptococcus pneumoniae (χ² = 11.872, p = 0.003); dual-positive, Klebsiella pneumoniae (χ² = 7.284, p = 0.009).

Conclusion: Pertussis and MP infections in children show distinct demographic, seasonal, clinical, and laboratory patterns. Recognition of these epidemiologic and clinical signatures supports early differentiation at the bedside and the use of multiplex PCR combined with specific laboratory markers to enable more targeted clinical management.

Background: As the principal cause of cervical cancer, human papillomavirus (HPV) infection is linked to vaginal infections such as bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), aerobic vaginitis (AV), and Trichomonas vaginalis (TV); however, the exact relationship remains controversial.

Methods: In this study, we performed a cross-sectional analysis of 10,104 women in Jinan, China, to establish a detailed association between HPV and vaginal infections.

Results: Our analysis showed that the HPV infection rate in Jinan was 21.84% of which the high-risk HPV (HR-HPV) infection rate was 84.32%. Although HR-HPV, low-risk HPV, BV, VVC, and TV prevalence rates across seasons were not statistically significant, we discerned significance for AV. In addition, while there was no difference between the prevalence of HPV and VVC, women with BV, AV, TV, or any vaginal infection manifested a higher risk of HPV infection. As for HR-HPV, our results showed statistically significant differences in HR-HPV infection rates between patients with BV, AV, TV, or any type of vaginal infection and the control group; however, VVC cases and cases without VVC did not differ. Furthermore, our correlation analysis among different HR-HPV genotypes and vaginal infections revealed an elevated incidence of BV in individuals with HPV45, HPV51, HPV52, HPV58, HPV66, and HPV68. AV exhibited an elevated infection rate in women with HPV16, HPV33, and HPV68; while TV demonstrated an increased infection risk in women with HPV52.

Conclusion: We hereby explored the complex relationship between HPV infection and vaginal infections and provided information on early-detection, preventive, and therapeutic strategies.

Introduction: Ceftazidime-avibactam represents a crucial therapeutic option for managing infections attributable to carbapenem-resistant P. aeruginosa. Nonetheless, the emergence of resistance to ceftazidime-avibactam in P. aeruginosa presents a significant challenge for clinical anti-infective therapy. This study primarily elucidates the mechanisms by which P. aeruginosa transitions from drug sensitivity to resistance during ceftazidime-avibactam treatment, ultimately resulting in therapeutic failure.

Methods: The susceptibility testing was performed using the broth microdilution method, conjugation experiment was performed via the filter mating method, the genetic surroundings of bla _KPC-249 and comparison of plasmids structures was performed using short/long-read genome sequencing and analysis method, the resistance of transconjugant carried the bla _KPC-249 to ceftazidime-avibactam was performed via molecular cloning method.

Results: For P. aeruginosa isolates from a patient, the minimum inhibitory concentrations (MICs) of ceftazidime-avibactam (CAZ-AVI) were determined as follows: isolates from sputum and bronchoalveolar lavage fluid both exhibited an MIC of 2 mg/L without blaKPC. In comparison, the blood-isolated strain P. aeruginosa PAE045 showed a significantly elevated MIC of >128 mg/L against CAZ-AVI. Plasmid conjugation experiments results demonstrated that the plasmid harboring the bla _KPC-249 gene could be successfully transferred to the recipient strain PAO1 ^rifR (rifampicin-resistant P. aeruginosa PAO1). Third-generation sequencing results revealed that the bla _KPC-249 gene was located on a plasmid with an approximate size of 37 kb. Compared with the wild-type e bla _KPC-2 gene, the bla _KPC-249 gene had two additional amino acid residues in its encoded protein: threonine (Thr, T) at position 182 and serine (Ser, S) at position 183. Furthermore, the upstream and downstream regions of the bla _KPC-249 gene were flanked by the insertion sequences ISKpn6 and ISKpn27, respectively.

Discussion: These mobile genetic elements may play a role in the capture and dissemination of the bla _KPC-249 gene. The bla _KPC-249 gene is identified as a novel mutant variant of the bla _KPC gene family, which mediates the resistance of P. aeruginosa to the antimicrobial agent ceftazidime-avibactam.

Background: Ubiquitination is a posttranslational modification that affects protein function, stability, and localization and is thereby balancing protein homeostasis. During infection, ubiquitination is crucial in regulating host cell signaling pathways in pathogen recognition, clearance and mounting an efficient immune response. S. aureus is an opportunistic pathogen that is able to invade and multiply within both phagocytic and non-phagocytic mammalian cells depending on virulence factor expression of the respective S. aureus strain. Selective autophagy serves as a host defense mechanism to combat intracellular bacterial persistence by targeting and degrading intracellular pathogens. However, S. aureus can subvert autophagosomal degradation and exploit these organelles for intracellular replication.

Results: We examined the role of the E3 ligase S-phase kinase-associated protein 2 (SKP2), a component of the SKP1-Cullin1-F-box (SCF) - complex, during S. aureus infection in alveolar epithelial and in macrophage-like cells. Upon S. aureus infection, we demonstrate increased SKP2 abundance through acetylation-induced stabilization and translocation into the cytoplasm. Cytoplasmic SKP2 modulated autophagy induction. By downregulation of SKP2, the level of the autophagy marker LC3-II was elevated which was accompanied by increased survival of intracellular S. aureus. Conversely, SKP2 overexpression in host cells reduced LC3-II levels followed by reduced intracellular bacteria.

Conclusion: These findings underscore that SKP2 is an important regulator of autophagosome formation, preventing excessive autophagy from being exploited by S. aureus. In conclusion, our findings reveal novel molecular mechanisms involved in the interaction between host cells and S. aureus providing potential approaches for targeted therapeutic intervention.

Background: Porcine reproductive and respiratory syndrome (PRRS) is a widely prevalent disease of reproductive failure of pregnant pigs and respiratory syndromes in pigs of different ages, especially in piglets. The etiological agents include PRRS virus (PRRSV) genotypes 1 (PRRSV-1) and PRRSV-2, whereas their clinical symptoms are similar and hard to differentiate. It is necessary to establish accurate and reliable methods for differential detection of PRRSV-1 and PRRSV-2.

Methods: Two pairs of specific primers and probes were designed basing on the PRRSV-1 and PRRSV-2 ORF6 gene. The reaction conditions and procedures of the duplex crystal digital PCR (cdPCR) were optimized. The specificity, sensitivity, and repeatability of the developed assay were evaluated. The application of the developed assay was assessed by testing 2,185 clinical tissue samples.

Results: The results indicated that the concentration of the templates and their Ct values had good linear relationship with R² of 0.998. This method could specifically detect PRRSV-1 and PRRSV-2, without cross-reaction with other swine viruses. The limits of detection (LODs) of the assay were 4.507 copies/reaction and 5.607 copies/reaction for PRRSV-1 and PRRSV-2, respectively, which was approximately 30 times more sensitive than that of the duplex real-time quantitative PCR (qPCR). The repeatability test showed that the intra- and inter-assay coefficients of variation (CVs) were 0.74%-0.93% and 0.63%-1.62%, respectively. This method was validated by testing 2,185 clinical samples from Guangxi Province in South China, and the positivity rates of PRRSV-1 and PRRSV-2 were 2.20% (48/2,185) and 23.43% (512/2,185), respectively. The coincidence rates of the developed assay with the qPCR assay recommended by the World Organisation of Animal Health (WOAH) were 99.73% and 99.73%, respectively, while with the duplex qPCR developed in this study were 99.82% and 99.77%, respectively.

Conclusions: These results indicated that a rapid and accurate duplex cdPCR method with high sensitivity and excellent specificity had been successfully developed for the differential detection of PRRSV-1 and PRRSV-2.