Frontiers in Cellular and Infection Microbiology最新文献

Introduction: Malaria remains a major global health burden and motivates fast, reliable in silico prioritization of antimalarial (AM) peptide candidates. Designing such peptides is challenging due to the vast search space, scarce or noisy supervision, and potential out-of-distribution miscalibration of computational scores. Prior pipelines typically rank existing sequences rather than generate new candidates under explicit design constraints with calibrated, risk-aware decision rules.

Methods: We propose a constraint-guided generate-then-classify framework. A low-data generator-an optimized variant of CTCM-Neo-proposes de novo sequences within APD3-derived windows for net charge, GRAVY, and Boman index. A frozen, temperature-scaled protein language-model classifier (ConformaX-PEP) outputs calibrated probabilities for predicted antimalarial activity and hemolysis, and a split-conformal gate with risk level α=0.1 converts these scores into accept/reject decisions at fixed operating thresholds p _act ≥ 0.78 and p _hemo ≤ 0.20.

Results: On the initial 322-sequence corpus (52 AM, 200 unlabeled, 70 positive-like), a held-out evaluation achieves AUROC ≈0.93, AUPRC ≈0.80, and ECE ≈0.03, indicating strong discrimination with low calibration error prior to external testing. The method outperforms strong baselines in convergence speed and reliability. On 210 previously unseen peptides (80 AM, 130 NM), two independent runs achieve 92.86% and 93.33% accuracy with balanced precision and recall and good calibration. Hyperparameter sweeps reveal broad, stable optima, supporting reproducibility. Template-based docking with GalaxyPepDock is used strictly as a hypothesis-generating structural sanity check and does not constitute evidence of biological binding or efficacy.

Discussion: Overall, the framework compresses the search space into a small, risk-bounded set of computationally prioritized candidates and provides a scalable, uncertainty-aware route for downstream experimental follow-up. All results reported here are computational, and antimalarial activity remains to be confirmed experimentally.

Introduction: Eravacycline (ERV) is a novel synthetic fluorocycline antibiotic with broad-spectrum antibacterial efficacy against pathogens. This study aimed to investigate the clinical effectiveness of eravacycline and its correlation with minimum inhibitory concentrations (MICs) against infections caused by Acinetobacter baumannii or Klebsiella pneumoniae.

Methods: This retrospective multicenter study investigated the real-world use of ERV in 1,796 adults with infection caused by A. baumannii or K. pneumoniae in China. Antimicrobial susceptibility of strains and laboratory test results during treatment were analyzed. Microbiological and clinical outcomes were assessed at the end of treatment and day 30.

Results: The overall susceptibility rate to ERV was 96.0% (1,027/1,070), and around 98% of carbapenem-resistant isolates were susceptible to ERV. ERV had a 4-fold lower MIC₉₀ than tigecycline against both pathogens. At end of treatment, treatment success (microbiological eradication or clinical resolution) occurred in 82.6% (1,483/1,796) of the cohort with microbiological eradication achieved 76.1% (789/1,037). At day 30, infection cure was achieved in 83.57% (1,501/1,796) of the cases. Different ERV regimens (monotherapy or concomitant therapy) had no influence on the treatment and 30-day clinical outcomes. Multivariable analysis identified that elevated C-reactive protein (CRP) levels during treatment, bloodstream infection, sepsis and specific clinical interventions (e.g., central venous catheterization) were independent predictors of treatment failure.

Conclusions: The study highlights ERV's utility in infection of A. baumannii or K. pneumoniae, especially carbapenem-resistant strains.

Objective: Diabetic foot ulcers (DFUs) represent a serious diabetic complication requiring effective therapeutic interventions. This systematic review and meta-analysis evaluates the clinical outcomes and safety profile of antibiotic-loaded bone cement (ALBC), an innovative localized drug delivery approach, for managing DFU patients.

Methods: From their inception through October 2025, a comprehensive literature search was conducted across multiple databases including PubMed, Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and CBM Database. Our analysis focused exclusively on randomized clinical trials that compared ALBC therapy with standard treatment protocols in diabetic foot cases. The primary endpoints assessed were wound healing time and clinical effective rate. Secondary outcome measures encompassed length of hospitalization, surgical intervention frequency, visual analog scale (VAS) for pain assessment, and limb preservation rates. Statistical analysis was performed using R statistical software with random-effects modeling to account for potential heterogeneity.

Results: 22 RCTs involving 1,295 patients were included. All studies were conducted in China. Pooled analysis demonstrated that ALBC significantly shortened wound healing time (Mean Difference [MD] = -7.10 days, 95% CI: -12.88 to -1.32, p = 0.016, I² = 96%) and improved the clinical effective rate (Odds Ratio [OR] = 4.05, 95% CI: 2.70 to 6.07, p < 0.001, I² = 9.9%) compared to control. Furthermore, ALBC reduced the number of surgeries. The standardized mean difference (SMD) was -1.88, with a 95% CI from -3.29 to -0.47. It also reduced hospital stay, with a mean difference (MD) of -8.56 days and a 95% CI from -12.33 to -4.79. The VAS pain score was reduced, with an SMD of -1.29 and a 95% CI from -1.89 to -0.69. Additionally, the amputation rate was reduced, with an odds ratio (OR) of 0.19 and a 95% CI from 0.07 to 0.50. Subgroup and sensitivity analyses generally supported the robustness of these findings. No significant publication bias was detected.

Conclusion: Antibiotic-loaded bone cement (ALBC) therapy demonstrates significant efficacy and safety in managing diabetic foot ulcers, promoting rapid tissue regeneration while minimizing adverse effects. This intervention correlates with enhanced wound closure rates, diminished pain perception, decreased surgical intervention frequency, reduced hospitalization duration, and lower extremity amputation incidence. Current evidence substantiates the clinical implementation of ALBC therapy; however, additional rigorously designed investigations are warranted to strengthen the external validity of these findings across diverse patient populations.

Chronic inflammatory gastrointestinal disorders, including inflammatory bowel disease (IBD), Crohn's disease, ulcerative colitis, and irritable bowel syndrome (IBS), remain challenging to manage due to complex etiologies, heterogeneous disease progression, and limitations in current diagnostic and therapeutic strategies. Existing clinical approaches rely on a combination of invasive and non-invasive diagnostic tools, while therapeutic management predominantly involves symptomatic control, disease-modifying pharmacotherapy, and surgical interventions. However, these strategies often fail to enable early or real-time disease detection and frequently fall short of achieving sustained remission. This review highlights two emerging and potentially transformative approaches: nanomedicine and living diagnostic-therapeutic systems. Nanomedicine has gained significant attention for its ability to enhance targeted drug delivery and improve therapeutic efficiency, addressing several limitations of conventional treatments; nevertheless, challenges related to delivery consistency, biosafety, scalability, and long-term efficacy persist. In parallel, living diagnostic-therapeutic systems-engineered whole-cell sensors capable of real-time sensing and on-demand therapeutic response within the gut-represent a compelling alternative. Although still at an early stage of development, promising preclinical and limited clinical studies demonstrate their potential utility. Key challenges remain, including biosensor functionality, genetic stability, microbial colonization, host-microbe interactions, and integration into existing healthcare frameworks, alongside regulatory and translational barriers. Overall, the convergence of nanomedicine and living, responsive systems may offer a transformative pathway for the diagnosis and treatment of chronic inflammatory gut diseases.

Reversible protein S-palmitoylation, mediated by protein acyl transferases (PATs) and depalmitoylases, is essential for regulating numerous biological processes, including subcellular localization, protein stability, enzymatic activity, and protein-protein interactions. While the study of S-palmitoylation in virology is extensive, less attention has been paid to its reverse process, depalmitoylation, at the virus-host interface. This review summarizes the dynamic regulatory mechanisms of both S-palmitoylation and depalmitoylation. We systematically review the functional consequences of these host enzyme-mediated modifications based on the roles of viral proteins in the viral life cycle. Next, we focus on how viruses exploit these modifications for immune evasion and the corresponding host antiviral strategies. Finally, we analyze the distinct role of depalmitoylation in regulating viral replication and host defense. Overall, this review aims to provide new insights into the regulatory mechanisms of reversible S-palmitoylation at the virus-host interface.

Introduction: Crohn's disease (CD) is commonly treated with biologic therapies, including anti-TNFα agents, vedolizumab (VDZ), and ustekinumab (USTE), yet only a subset of patients respond to these treatments. This study aimed to evaluate the potential of the gut microbiome to predict treatment response.

Methods: Adult CD patients initiating anti-TNFα (infliximab or adalimumab), VDZ or USTE were enrolled. Pre-treatment ileal and/or colonic biopsies were collected endoscopically. Treatment response after 26-52 weeks was defined by ≥50% reduction in the simple endoscopic score for CD and either a corticosteroid-free clinical response (≥3-point HBI decrease or remission [HBI ≤4] without systemic steroids) or a biochemical response (≥50% or ≤5 mg/L CRP reduction and ≥50% or ≤250 μg/g faecal calprotectin reduction) versus baseline. Mucosal microbiota was profiled by 16S rRNA gene sequencing of biopsies. Machine learning models predicting treatment response were trained using ASV-level count data. The impact of heat-killed bacteria on anti-TNFα-induced CD14⁺CD206⁺ macrophages was tested in mixed lymphocyte reactions (MLRs).

Results: A total of 125 patients were included: 39 on anti-TNFα, 47 on VDZ, and 39 on USTE. Clinical features were similar between responders and non-responders, aside from sex (USTE-colon) and CRP (USTE-ileum). No major microbial differences were observed in VDZ, USTE ileal or colon samples. However, in colonic biopsies, anti-TNFα responders had significantly higher pre-treatment α-diversity, and 3.9% of β-diversity variation associated with response. Among six models, the anti-TNFα colonic model performed significantly better than random (AUC = 0.90) to predict response. Mediterraneibacter gnavus ASVs associated with non-response, whereas Blautia ASVs associated with response, to anti-TNFα. When tested in MLRs, pretreatment with M. gnavus and B. luti led to a reduction in macrophage polarization, with a significantly stronger effect observed for M. gnavus compared with B. luti.

Discussion: Taken together, this study demonstrates that the colonic mucosal microbiome prior to anti-TNFα treatment can distinguish responders from non-responders in CD, supporting its potential as a predictive biomarker.

Nocardia species are opportunistic pathogens that cause localized and disseminated infections, particularly in immunocompromised individuals. Despite their clinical importance, the molecular mechanisms underlying Nocardia pathogenicity remain incompletely understood. This review summarizes current advances in Nocardia virulence factors, host immune responses, and intracellular survival strategies. A diverse array of virulence factors enables Nocardia to invade host cells, circumvent immune defenses, and maintain persistence within host tissues, including mammalian cell entry (Mce) proteins, antioxidant enzymes, phospholipase C, hemolysins, and siderophore-associated proteins. Host protection against Nocardia relies primarily on innate immune responses, with neutrophils playing a central role and being coordinated by γδT cells and interleukin-17-mediated signaling pathways. In addition, the clinical epidemiology of nocardiosis and animal models of Nocardia infection are also briefly summarized. However, most mechanistic studies remain restricted to a limited number of type strains. Further investigations into Nocardia-host interactions are essential for the development of improved diagnostic, therapeutic, and preventive strategies for nocardiosis.

Extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) present increasing incidence and limited therapeutic options, emerging as one of the serious public health threats worldwide. Here, we report a case of an elderly male patient with multiple primary diseases who developed a severe pneumonia following long-term bedrest due to an accidental tumble after cerebral infarction. In the meantime, plenty of Gram-negative bacilli were repeatedly detected in his sputum and rapidly spread into his blood. This strain was ultimately identified as New Delhi metallo-β-lactamase (NDM) positive XDR-PA. Subsequently, the patient was treated with a combination of ceftazidime-avibactam (2.5 g q8h) and high-dose aztreonam (2 g q6h) under close supervision on his hepatorenal function. No dose adjustment was made throughout the treatment course. After one week of therapy, the patient's symptoms were remarkably resolved, and finally discharged. This is the first evidence worldwide of successful treatment for severe pneumonia caused by NDM positive XDR-PA using this dose-dependent combination therapeutic regimen as far as we know. The accurate and timely results of carbapenemase typing and combined antimicrobial susceptibility testing support our bold attempt at this novel treatment regimen, ultimately making the patient recover with a favorable prognosis.

Introduction: With the rapid development of 16S rRNA sequencing and metagenomic technologies, the traditional concept of sterile urine has been completely overturned, and a diverse urinary microbiome has been identified even in healthy individuals. Increasing evidence indicates that dysbiosis of the urinary microbiome is closely associated with the onset and progression of various non-infectious urological diseases.

Methods: This review systematically summarizes recent advances in the role of the urinary microbiome in non-infectious urological diseases, including bladder cancer, benign prostatic hyperplasia, prostate cancer, nephrolithiasis, interstitial cystitis/bladder pain syndrome, and urinary incontinence, with a focus on microbial dysbiosis, pathogenic mechanisms, and clinical applications.

Results: Studies have shown that alterations in the composition and diversity of the urinary microbiome are closely related to chronic inflammation, immune dysregulation, metabolic disturbances, and changes in the local microenvironment. These alterations may contribute to disease pathogenesis through mechanisms such as persistent low-grade inflammation, abnormal metabolic activity, and biofilm formation. In recent years, non-invasive detection based on urinary microbial profiles has shown promising potential in the early diagnosis of bladder and prostate cancers, with some machine learning models achieving diagnostic accuracies above 80 percent. Furthermore, the urinary microbiome may influence the efficacy of immunotherapy, offering new insights for personalized precision medicine.

Conclusions: This review summarizes the mechanisms, research status, and clinical prospects of the urinary microbiome in non-infectious urological diseases, emphasizing the importance of methodological standardization and highlighting its potential applications in early screening, diagnostic stratification, and microbiome-targeted interventions.