Frontiers in Cellular and Infection Microbiology最新文献

Tuberculosis is an infectious disease spread through airborne droplet nuclei. Mycobacterium tuberculosis is the etiological agent of this infection. Mycobacteria can cause active tuberculosis or asymptomatic latent infection due to its complex biology and host immunological responses. The genes of mycobacteria can change alveolar macrophages and boost their resistance to autophagosome-lysosome fusion. However, only 5%-10% of infected individuals progress to the active form. In this context, multiple factors are associated with the progression of the disease. Thus, the review aims to analyze the essential factors linked to the progression from latent to active tuberculosis. The mycobacterium genome closely links these factors. Importantly, mycobacteria possess numerous genes to act as a self-defense mechanism against autophagosome-lysosome fusion. The PE_PGRS proteins play an essential role in this mechanism. This protein, when combined with Rab1A, helps activate Rab1A GTP, hence boosting mTOR and preventing autophagy. The presence of certain miRNAs, probably miR-142-3p, reduced the development of the phagosome in macrophages; circRNA-0003528 helped change macrophages related to Mycobacterium by increasing CTLA4 and decreasing miR-224-5p, miR-324-5p, and miR-488-5p. Single-cell technologies like RNA sequencing can properly examine adaptive immune cell types in healthy people and patients, including CD4+, CD8+ T, and B cells. Deficiency of CD4+ T cells increases the risk of TB and can transform an infection into active tuberculosis. Therefore, research on autophagy-regulated genes and T-cell-mediated immune response, along with transcriptome analyses will determine the pathogenesis of tuberculosis, differentiate between active and latent TB, and facilitate the critical role of diagnostic biomarkers.

Background: Diabetic foot osteomyelitis (DFO) is a serious complication of diabetes and a leading cause of lower-limb amputations. Conventional culture-based diagnostics often underestimate the microbial diversity of infected bone tissue. This study represents the first characterization of both total and ribosomally active bone microbiota in Hispanic patients with DFO using high-throughput 16S rRNA gene sequencing. The work aims to contribute to the inclusion of underrepresented populations in microbiome research and informing molecular-based antimicrobial strategies.

Methods: Bone specimens (n = 13) were collected from seven Chilean patients with histologically confirmed DFO. Samples were analyzed using conventional aerobic culture and 16S rRNA gene sequencing from both genomic DNA (gDNA) and complementary DNA (cDNA) to characterize the total bacterial community and the ribosomally active fraction. In three patients, samples were stratified by bone depth (superficial/top, middle and bottom). Microbial diversity and relative abundance were assessed across patients and bone layers.

Results: Acute osteomyelitis was the predominant histopathological pattern. Culture yielded 19 bacterial isolates, 95% of which were Gram-negative bacilli. Sequencing identified 3,412 operational taxonomic units (OTUs), with Proteobacteria, Bacteroidetes, Firmicutes, and Actinobacteria as dominant phyla. Enterobacteriaceae and Enterococcaceae were the most ribosomally active families. Microbial community composition varied substantially among patients and across bone depths. Staphylococcus aureus was infrequent (5% of culture isolates; ~1% of sequence reads), whereas low-abundance but ribosomally active taxa, such as Corynebacteriaceae, were consistently detected across all layers.

Discussion: This combined metagenomic and ribosomal transcript analysis reveals a polymicrobial, patient-specific bone microbiota in Chilean patients with DFO, highlighting potentially active bacteria frequently overlooked by standard diagnostic methods. These findings underscore the value of integrating molecular approaches into clinical workflows to improve pathogen detection and support more personalized antimicrobial strategies, while also helping to address gaps in microbiome research among underrepresented populations.

Background: Malaria remains a persistent health challenge in southern Saudi Arabia, particularly along the border with Yemen. Understanding the genetic diversity and population structure of Plasmodium falciparum antigens is essential for tracking transmission dynamics and informing vaccine design. This study characterises population genetics of the Cell-Traversal Protein for Ookinetes and Sporozoites (CelTOS) gene in Jazan Province, a region of active transmission and frequent cross-border movement.

Methods: We analysed 202 high-quality P. falciparum CelTOS coding sequences from 201 patients in Jazan. Diversity indices and neutrality tests were estimated in DnaSP, and demographic history was assessed using mismatch-distribution models (SSD, raggedness). Gene-wide dN/dS (ω) was derived from MEGA pairwise distances, and recombination was evaluated using PHI and GARD. Recombination-aware codon-based models (SLAC, FEL, MEME, and FUBAR) were implemented via Datamonkey. Population structure was examined using pairwise F_ST, AMOVA, principal coordinate analysis (PCoA), and PERMANOVA. Haplotype networks were stratified by nationality, parasite density, region, and season, and parasitaemia correlates were explored using multivariable regression.

Results: The 726-bp CelTOS alignment contained 18 segregating sites and 27 haplotypes (Hd = 0.921; π = 0.0059). Gene-wide ω was ≈0.36, consistent with predominant purifying selection, with only a few codons showing episodic diversifying selection. The mismatch distribution was unimodal (SSD = 0.029; raggedness = 0.0487), and recombination tests indicated low-level intragenic recombination (PHI p = 1.44 × 10^-5; Rm = 4). Pairwise F_ST values were essentially zero, and PERMANOVA showed a weak, non-significant regional structure. Dominant CelTOS haplotypes were shared across nationality, density, and regional and seasonal strata. In the main logistic model (PD4 vs. PD1-PD3), age (OR 1.03; 95% CI 1.00-1.06) and non-Saudi nationality (OR 2.21; 95% CI 1.02-4.81) showed modest associations with very high parasitaemia.

Conclusions: CelTOS diversity in Jazan is characterised by high haplotype but low nucleotide diversity within a largely panmictic, recombining parasite population. Extensive haplotype sharing across demographic and ecological gradients underscores strong gene flow, supporting cross-border, year-round control strategies and highlighting CelTOS as a relevant marker for vaccine development and molecular surveillance in this elimination setting.

As fungal diseases emerge, new studies aim to understand how different metabolic pathways, including the biosynthesis of phospholipids, influence the fungal pathogenicity. Therefore, to investigate the role of phosphatidylcholine (PC) in the biology of the human fungal pathogen Cryptococcus neoformans, a double mutant lacking OPI3 (phosphatidylethanolamine methyltransferase) from the de novo pathway, and PCT1 (choline phosphate cytidylyltransferase) from the salvage Kennedy pathway was generated using double-joint PCR coupled with biolistic technique for gene deletion. Phenotypic and virulence assays were performed, including growth viability in minimal nutrient, melanization, capsule expansion and titanization, lipid droplet analysis and in vivo infection in larval and murine models. The double mutant (opi3Δpct1Δ) exhibited normal growth in complex medium, but displayed severe growth defects and loss of viability under nutrient-limited conditions. Supplementation with L-α-glycerophosphorylcholine (GPC), PC or sorbitol fully restores growth, suggesting compensation of GPC-dependent reacylation pathway. Disruption of PC biosynthesis affected important virulence traits, including capsule formation, melanization, and titan cell development, and increased susceptibility to membrane stresses. In vivo, in both the Galleria mellonella and murine models, opi3Δpct1Δ was hypovirulent with reduced brain colonization. Other studies with C. neoformans and Candida albicans, another pathogenic yeast, showed no impact in deletion of either OPI3 or PCT1 alone for virulence and pathogenicity. Therefore, these findings highlight the critical role of PC biosynthesis for maintaining membrane integrity, morphological plasticity and host dissemination of C. neoformans.

Background: Despite global recommendations for maternal tetanus-diphtheria-acellular pertussis (Tdap) vaccination to protect neonates, safety concerns persist regarding pregnancy-specific adverse events (AEs). We conducted a 20-year analysis of U.S. Vaccine Adverse Event Reporting System (VAERS) data (2005-2024) to characterize Tdap-associated AEs during pregnancy, with emphasis on understudied outcomes like chorioamnionitis.

Methods: We analyzed 870 pregnancy-related reports (128 serious) from 20,358 Tdap submissions using disproportionality analysis (Reporting Odds Ratio, ROR). Cases were identified via MedDRA-coded terms and free-text mining. Outcomes were stratified by System Organ Class (SOC), trimester, and AE seriousness. Novel signals were evaluated against product labeling and prior studies.

Results: 71.9% of AEs occurred within 30 days post-vaccination. No AEs of maternal death were found. Strong safety signals stillbirth (ROR 285.77, IC 8.01), preterm delivery (ROR 196.8, IC 7.51), and fetal death (ROR 140.83, IC 7.06) were found via disproportionality from a passive surveillance system, which required further validation in active surveillance studies. Pregnancy-specific AEs represented 22.3% of significant PTs, including 6 chorioamnionitis cases with most cases having documented obstetric risk factors. Novel signals fetal hypokinesia and urinary tract infection emerged as unlabeled risks.

Conclusion: This analysis affirms Tdap's favorable safety profile while detecting statistically significant signals that merit additional research. The low absolute risk supports continued maternal immunization, but warrants enhanced monitoring in high-risk pregnancies. The findings highlight the importance of ongoing post-marketing surveillance for evaluating vaccine safety in pregnant populations and contribute to evidence-based decision-making in clinical practice and public health policy.

Objectives: Invasive Klebsiella pneumoniae liver abscess syndrome (IKPLAS) is a life-endangering condition. This meta-analysis sought to identify factors that could potentially serve as risk factors for IKPLAS.

Methods: Eight databases were retrieved. The Newcastle-Ottawa Scale and AHRQ criteria were utilized to assess the studies for quality. Stata software was used for pooling the effect size odds ratio (OR) and for subgroup analysis, sensitivity analysis, and regression analysis. Publication bias was examined leveraging funnel plots and Egger's test.

Results: A total of 18 studies (cross-sectional, cohort, case-control studies) were included, with 3,133 patients. The meta-analysis revealed that the following factors were linked to a significantly elevated risk of IKPLAS: history of smoking or alcohol consumption (OR = 1.61, 95% CI: 1.05, 2.45, p = 0.028), diabetes (OR = 1.93, 95% CI: 1.49, 2.51, p<0.001), liver disease (OR = 1.66, 95% CI: 1.01, 2.73, p = 0.044), elevated sequential organ failure assessment (SOFA) score (OR = 1.71, 95% CI: 1.27, 2.30, p<0.001), septic shock (OR = 3.30, 95% CI: 1.70, 6.37,p<0.001), hepatic abscess in the left lobe (OR = 1.51, 95% CI: 1.02, 2.24, p = 0.039), phlebitis (OR = 21.01, 95% CI: 10.24, 43.11, p<0.001), procalcitonin (PCT) (OR = 1.01, 95% CI: 1.01, 1.02, p<0.001), fasting blood glucose (FBG) (OR = 1.21, 95% CI: 1.11, 1.32, p<0.001), prothrombin time (PT) (OR = 1.15, 95% CI: 1.01, 1.30, p = 0.032), total bilirubin (OR = 1.02, 95% CI: 1.01, 1.02, p<0.001), hypervirulent phenotype (OR = 2.17, 95% CI: 1.15, 4.10, p = 0.017), K1 serotype (OR = 4.79, 95% CI: 1.79, 12.76, p = 0.002). No other risk factors were found.

Conclusion: This study identified multiple risk factors significantly associated with IKPLAS, providing evidence for risk assessment and prevention strategies.

Background: Infections due to multidrug- and extensively drug-resistant bacteria can be difficult to treat and are associated with high mortality and burden of disease. Ceftazidime-avibactam (CVA) is used in patients with multidrug-resistant Gram-negative bacterial infections.

Objective: To describe the real-world usage, effectiveness, and antimicrobial features of CVA in clinical practice in China.

Methods: This multicenter, prospective observational study collected medical record data from adult patients (≥18 years) who had been hospitalized and treated with ≥1 dose of CVA. Clinical and microbiological outcomes were evaluated at the end of treatment, with clinical cure defined as resolution of infection following treatment with CVA.

Results: Data were obtained from 220 adult patients receiving ≥1 dose of CVA in China. Infections indicated for CVA included pneumonia (64.5%), complicated intra-abdominal infection (16.8%) and bloodstream infection (7.3%). Klebsiella pneumoniae (129/227 isolates, 56.8%) was the most commonly identified pathogen, followed by Pseudomonas aeruginosa (33 isolates, 14.5%). Of 87 K. pneumoniae isolates, 76 (87.4%) were meropenem resistant and the same proportion carried cabapenemase genes. Low levels of resistance to CVA were observed across all isolates. Three-quarters of patients received CVA as definitive therapy. Clinical cure at end of treatment was achieved in 66.4% of patients and microbiological success in 69.6% of patients.

Conclusion: Findings from this study provide important real-world data on treatment patterns, microbiological features, and clinical and microbiological outcomes for CVA in routine clinical practice in China.

Objective: Through the machine learning Least absolute shrinkage and selection operator (LASSO) algorithm, the system screened core prognostic risk factors for patients with ischaemic stroke and bloodstream infection, constructed and validated a predictive model, provides a basis for formulating precise risk management strategies in clinical practice.

Methods: Clinical data from patients with bloodstream infections secondary to ischaemic stroke were retrospectively included. The dataset was randomly allocated into training and validation sets at a 7:3 ratio. Within the training set, Model 1 was constructed using traditional univariate and multivariate Cox regression methods, while Model 2 employed the machine learning LASSO regression algorithm. Models were compared using metrics including R-squared, C-index. The superior model was selected for validation on both training and validation sets using Area Under the Curve (AUC) of the receiver operating characteristic curve, calibration curves, and Decision-Making Curves (DCA).

Results: Model 2 was adopted as the final model, with a nomogram generated for the training set. As demonstrated by the nomogram, an increase in the total score was observed in patients with concomitant pneumonia, heart failure (HF), or coronary atherosclerotic heart disease (CHD), in cases where mechanical ventilation (MV) was utilised, and in instances of elevated alanine aminotransferase (ALT) and C-reactive protein-lymphocyte ratio (CLR) values, and reduced albumin levels. In the training set, the AUC values for predicting 7-day, 14-day, and 28-day survival rates were 0.875, 0.886, and 0.861, respectively. The AUC value for the 28-day prognosis on the internal test set was 0.844, while that on the external validation dataset was 0.860. The model demonstrated high concordance between predicted and actual probabilities across three distinct cohorts. The clinical decision curve indicates that the model provides good net benefit within the 5%-25% range at all three time points (7,14,and 28 days) across the three datasets.

Conclusion: Comorbidities such as pneumonia and hypoalbuminaemia constitute prognostic risk factors affecting patients with ischaemic stroke and bloodstream infections. LASSO regression enables precise identification of these risk factors, yielding a prognostic prediction model with outstanding predictive efficacy and clinical utility. Clinicians may utilise model variables to implement targeted risk management strategies.

Introduction: GII noroviruses (NoVs) are the leading cause of viral gastroenteritis worldwide. A critical unresolved question is whether natural infection elicits long-lasting protective antibodies, which is paramount for guiding vaccine development. The long-term persistence of functional neutralizing antibodies against the predominant GII genogroup remains poorly characterized.

Methods: In a 5-year community-based prospective cohort (2014-2018), we longitudinally assessed seroprevalence, seroincidence, and persistence of blockade antibodies against GII.4, GII.6, and GII.17 NoVs in 449 adults. HBGA (human histo-blood group antigen) associations with susceptibility were also analyzed.

Results: GII.4 exhibited the highest and most stable seroprevalence (77.3-79.7%), while GII.17 seroprevalence rose sharply from 41.9% to 72.2%, capturing its emergence as an epidemic strain. Seroincidence was substantial, highest for GII.17 (30.4 per 100 person-years). In contrast to GI NoVs, GII.4 and GII.17 antibody exhibited exceptional persistence, with five-year persistence rate of 94.5% for GII.4 and 81.4% for GII.17, respectively, and no significant decay in blockade activity-both significantly exceeding the 61.2% persistence of GII.6. HBGA susceptibility patterns were distinct: GII.4 and GII.6 were associated with secretor status and Lewis antigens, while only blood type A was linked to GII.17 susceptibility.

Conclusion: This study provides the first longitudinal evidence that natural infection with major GII NoVs, particularly GII.4 and the emerging GII.17, elicits robust and sustained functional antibody responses that persist for at least five years. This fundamental genogroup-specific disparity in immune durability, contrasting sharply with transient GI immunity, reveals a new dimension of NoVs immunology and provides a critical evidence base for the design of effective, long-lasting vaccines.

Background and aims: Fatty liver (FL) is a common comorbidity that has been associated with adverse clinical outcomes in various liver diseases. However, its impact on the prognosis of acute hepatitis B (AHB) remains unclear. This study aimed to evaluate the influence of FL on liver-related outcomes among hospitalized patients with AHB.

Methods: A retrospective analysis was conducted on hospitalized patients diagnosed with AHB from January 1, 2010, to December 30, 2023. Demographic and clinical data were collected, and patients were categorized into AHB with FL (AHB-FL) and AHB without FL (AHB-no FL) groups based on imaging and laboratory examinations. Multivariate regression models were utilized to investigate the association between FL and liver-related outcomes, including acute liver failure (ALF), hepatitis B surface antigen (HBsAg) loss, and seroconversion. Kaplan-Meier analysis was performed to assess differences in time to HBsAg loss and seroconversion.

Results: A total of 200 eligible patients were included, with 29 (14.5%) in the AHB-FL group and 171 (85.5%) in the AHB-no FL group. The incidence of ALF was significantly higher in the AHB-FL group (34.5% vs. 15.8%, P = 0.02). No significant differences were observed in rates of HBsAg loss (75.9% vs. 82.5%, P = 0.40) or seroconversion (44.4% vs. 53.1%, P = 0.40) between the two groups. Kaplan-Meier analysis indicated comparable times to HBsAg loss (P = 0.07) and seroconversion (P = 0.43). Multivariable analysis confirmed FL as an independent risk factor for ALF (OR 4.61, 95% CI 1.26-16.86; P = 0.02), but not for HBsAg loss (HR 1.60, 95% CI 0.92-2.78; P = 0.10) or seroconversion (HR 1.69, 95% CI 0.80-3.57; P = 0.17). Subgroup analysis indicated a stronger association between FL and ALF in rural patients (P interaction=0.02), suggesting regional differences may affect clinical risks and management.

Conclusion: FL constitutes a robust and independent determinant of ALF in AHB patients, sustained after rigorous adjustment for confounding factors. This evidence highlights a specific metabolic aggravation of liver injury, mandating the integration of FL screening into early risk stratification and management protocols.