Frontiers in Cellular and Infection Microbiology最新文献

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.

Human papillomavirus (HPV) infection is a major global health concern due to its association with various cancers, particularly cervical and head and neck squamous cell carcinomas. High-risk HPV types, such as HPV16 and HPV18, employ oncoproteins E6 and E7 to disrupt host cell regulatory pathways, promote immune evasion, and facilitate malignant transformation. Natural killer (NK) cells, critical components of innate immunity, play a pivotal role in surveilling and eliminating HPV-infected cells. However, HPV-mediated immune evasion mechanisms, including downregulation of MHC-I, suppression of chemokine signaling (e.g., CXCL14), and upregulation of inhibitory molecules (e.g., TIGIT, KLRG1), impair NK cell functionality. This review explores the intricate interactions between HPV and NK cells, highlighting the impact of HPV on NK cell infiltration, exhaustion, and receptor expression. Additionally, it discusses emerging therapeutic strategies to enhance NK cell activation, such as pharmacological agents (e.g., γ-PGA, α-GalCer), innate immune agonists (e.g., STING, RIG-I), genetic engineering (e.g., CAR-NK, iPSC-NK cells), and combination therapies with immune checkpoint inhibitors or monoclonal antibodies (e.g., cetuximab). Clinical applications, including adoptive NK cell transfer and biomarker-guided personalized immunotherapy, are also reviewed. Despite challenges like immunosuppressive tumor microenvironments and limited NK cell persistence, advancements in genetic engineering and nanoparticle delivery systems offer promising solutions. Future research should focus on integrating mechanistic insights with clinical trial design to optimize NK cell-based therapies for HPV-associated malignancies.

Tuberculosis remains a prevalent and serious chronic bacterial infection worldwide. Despite significant advancements in TB treatment in recent years, it continues to pose a major public health challenge. The onset and progression of TB are closely associated with individuals who are immunocompromised, as most patients also present comorbidities such as HIV, diabetes mellitus, and nutritional deficiencies. Consequently, the development of new, non-toxic immunomodulatory drugs or treatment strategies may offer viable solutions to these issues. Vitamin D not only plays a crucial role in regulating calcium and phosphate metabolism while maintaining bone health but is also a key regulator of the innate immune response against microbial infections. Furthermore, many tuberculosis patients exhibit low levels of vitamin D; thus, vitamin D may represent an important resource for enhancing immune responses against Mycobacterium tuberculosis infections. This review discusses the immune response mechanisms, vitamin D synthesis processes, and metabolic pathways activated in hosts following infection with M. tuberculosis. It emphasizes how vitamin D contributes to immune regulation and its potential role in combating M. tuberculosis infections within the human body. This literature review aims to provide theoretical support for developing new drugs and treatment strategies for clinical management of anti-M. tuberculosis infections.

Objectives: To elucidate the molecular epidemiology, virulence repertoire and resistance gene characteristics of carbapenem-resistant Enterobacter cloacae complex (CRECC) in bloodstream infections (BSI), thereby providing evidence for precision therapy and infection control.

Methods: We retrospectively collected 13 non-replicate CRECC-BSI isolates from January 2019 to December 2023 at a tertiary-care hospital in Shandong Province, China. Antimicrobial susceptibility was determined by broth microdilution; Illumina NovaSeq whole-genome sequencing was performed, and genomes were assembled with ABySS and GapCloser. ResFinder, VFDB, CGE and NCBI Pathogen Detection databases were used jointly to analyze resistance genes, virulence factors, plasmid replicons, MLST an SNP-based phylogenetic tree assessed inter-strain relatedness; while filter-mating assays determined the transferability of plasmids.

Results: A total of 13 CRECC isolates yielded five sequence types (STs), with ST171 predominating (46.2%, 6/13); all carried bla _NDM (bla _NDM-1 in 9 isolates, bla _NDM-5 in 4), along with AmpC, ESBLs, and aminoglycoside/quinolone resistance genes. The IncX3 plasmid replicon was most frequent (46.2%, 6/13), followed by IncHI2/HI2A (38.5%, 5/13). Each strain harbored adherence, biofilm formation, iron/manganese transport and T6SS virulence genes. Antimicrobial susceptibility testing revealed complete resistance among all isolates to cephalosporins, carbapenems and β-lactam/β-lactamase-inhibitor combinations, while amikacin, tigecycline and polymyxin B remained 100% susceptible. cgMLST revealed a polyclonal population structure. Conjugation assays demonstrated transfer of bla _NDM-bearing plasmids to recipient Escherichia coli J53.

Conclusions: Our institutional CRECC-BSI is characterized by diverse sequence types, a complex plasmid profile and a high burden of virulence genes; ST171 is the dominant clone and bla _NDM-1 the principal carbapenemase. Close surveillance of this high-risk lineage and of IncX3/IncHI2-mediated horizontal gene transfer is essential, together with strengthened infection-control and antimicrobial-stewardship measures.

Introduction: The optimization of neutralizing monoclonal antibodies (NMAbs) is crucial to counter viral evolution. The structural stability of the heavy-chain complementarity-determining region 3 (H3 CDR) significantly influences affinity maturation potential, yet its impact on computational optimization remains unclear.

Methods: This study employed an artificial intelligence (AI) model to optimize two categories of SARS-CoV-2 NMAbs: one featuring a conformationally stabilized H3 CDR via a twin cysteine motif, and another with flexible H3 CDR loops. Optimized antibody derivatives were evaluated for binding affinity to the SARS-CoV-2 spike protein, pseudovirus and live virus neutralization, and in vivo efficacy in a murine infection model. Structural analyses were conducted to elucidate interaction mechanisms with the angiotensin-converting enzyme 2 (ACE2) receptor.

Results: H3 CDR stabilization via twin cysteines markedly enhanced AI-driven optimization efficacy. Optimized derivatives from the stabilized antibody category exhibited improved binding affinity and superior neutralization potency against both pseudotyped and authentic SARS-CoV-2 viruses. Structural analyses revealed optimized antibodies formed tighter interactions with the ACE2 receptor, including enhanced binding between key residues and ACE2, which correlated with biological efficacy. In contrast, antibodies lacking H3 CDR stabilization showed no affinity improvement after the same optimization process. In vivo, optimized antibodies effectively suppressed viral replication and reduced viral loads in infected mice. Mechanistically, the twin cysteine stabilization minimized structural perturbations caused by affinity-enhancing mutations, unlocking the optimization potential of the H3 CDR.

Discussion: These findings establish that conformational stabilization of the H3 CDR in seed antibodies is a critical determinant for successful AI-driven affinity maturation. The study proposes a strategic framework for antibody development that prioritizes structurally stabilized H3 CDR regions, offering a robust approach to generating high-potency therapeutics against rapidly evolving viral pathogens.

Introduction: Both pulmonary tuberculosis (PTB) and sarcoidosis (SA) are chronic, systemic, granulomatous diseases. Due to their similar clinical and radiological features, as well as similar pathological characteristics, it is difficult to distinguish. This study aims to explore the pathological correlation between PTB and SA and the impact of nodules formation on the occurrence of PTB.

Methods: We retrospective enrolled 307 patients admitted to the tuberculosis department between January 2022 and March 2024. After applying the inclusion and exclusion criteria, 170 patients were divided into three groups and analyzed: sarcoid tuberculosis group (TB-N, n=59), non-sarcoid tuberculosis group (TB-NoN, n=74), and sarcoidosis group (SA, n=37). Comparative analysis was performed on the clinical characteristics, pathogen profiles, and pulmonary microbial composition differences among the three groups.

Results: Patients in the TB-N and SA group predominantly presented with multiple nodules. Among samples testing positive by both mNGS and conventional microbiological tests (CMT), the proportion of partially matched results was higher in the TB-N group than in the TB-NoN group, with a greater diversity of pathogenic bacteria detected in the TB-N group. ACE index analysis revealed significantly higher microbial richness in the TB-NoN group compared to both SA and TB-N groups. Regarding treatment regimens, combination therapy was more frequently administered in the TB-N group, while single drug treatment predominated in the TB-NoN group. Although the duration of anti-tuberculosis treatment was longer in the TB-N group, this difference did not reach statistical significance.

Discussion: Significant differences in imaging manifestations were observed between TB-N and SA groups. The presence of nodules was associated with a more complex pathogen profile in PTB patients; however, the pulmonary microbial diversity was lower in TB-N than in TB-NoN. PTB patients with nodules predominantly received combination therapy.

Scanning electron microscopy (SEM) is re-emerging as an accessible method in bacteriology, driven by technological advances that produced the powerful and compact tabletop SEM. This review highlights recent advances (2015-2025) demonstrating how novel tabletop SEM delivers rapid, high-resolution, and accurate results that can transform both fundamental and clinical bacteriology. Several studies consistently demonstrate the utility of tabletop SEM in basic research, such as studying biofilms, building antibacterial coated material, and describing bacteria-environment interactions. In clinical bacteriology, diverse applications have emerged over the past few years placing the tabletop SEM at the forefront of bacterial visualization from clinical samples, reaching accurate descriptions of bacteria-antibiotic interactions and the accurate detection of bacterial morphologic changes following exposure to antimicrobial agents with dramatically reduced turnaround times. When combined with energy-dispersive X-ray spectroscopy (EDX), tabletop SEM offers insights into bacterial metabolic states and chemical composition under stress or antimicrobial treatment. In this new era of bacteriology, tabletop SEM truly marks the return of a forgotten ally, empowering the investigative arsenal with speed, robustness, and accuracy in both research and clinical practice.

Objective: This study aimed to analyze the distribution characteristics and dynamic trends of antimicrobial resistance among pathogens isolated from blood cultures of adult patients at a large tertiary hospital in southern Jiangxi Province, China, from 2020 to 2024, in order to provide evidence-based guidance for the prevention and treatment of bloodstream infections.

Methods: This study conducted a retrospective analysis of non-repetitive isolates from blood cultures of adult patients at a large tertiary hospital in southern Jiangxi Province between 2020 and 2024. Statistical analysis was performed using WHONET 5.6 and SPSS Statistics 30 software.

Results: This study included a total of 3,695 pathogenic bacteria, with Gram-negative bacteria predominating (61.92%,2,288/3,695). Among Gram-negative bacteria, Escherichia coli (28.99%,1,071/3,695) and Klebsiella pneumoniae (14.72%,544/3,695) were the most prevalent. Antimicrobial resistance analysis revealed that the detection rate of carbapenem-resistant Klebsiella pneumoniae (CRKP) surged sharply from 1.2% (1/82) in 2020 to 21.8% (26/119) in 2024; the detection rate of carbapenem-resistant Acinetobacter baumannii (CRAB) increased from 33.3%(5/15) in 2020 to 76.5% (13/17) in 2024. In contrast, the detection rate of methicillin-resistant Staphylococcus aureus (MRSA) decreased significantly from 24.3% (17/73) in 2020 to 13.5% (10/74) in 2024. Among Enterococci, the rate of high-level gentamicin resistance (HLGR, defined as resistance to 500 µg/ml gentamicin) in Enterococcus faecium increased significantly, from 10% (1/10) in 2020 to 66.7% (14/21) in 2024, and vancomycin-resistant Enterococcus faecium (VREfm) was detected at a rate of 9.5% (2/21) in 2024.

Conclusion: In a tertiary hospital in southern Jiangxi, China, Gram-negative bacteria predominate among Patients with positive blood cultures, with sharply rising detection rates of CRKP, CRAB, and VREfm posing a public health threat. Meanwhile, the declining prevalence of MRSA indicates that infection control measures are effective against Gram-positive bacteria. Therefore, continuous surveillance of drug-resistant bacteria is essential, and antimicrobial stewardship measures must be implemented immediately to curb their spread. A limitation of this study is that it was conducted at a single center, which may restrict the generalizability of the findings to other regions.

Objectives: Since 2016, China has provided timely HIV antiretroviral therapy (ART) under the treat-all policy. This study aimed to evaluate the impact of rapid ART initiation (≤7 days post-HIV diagnosis) on loss to follow-up (LTFU), mortality, and virologic failure compared with that of delayed ART.

Methods: This study included adults with ART-naive HIV infection in Xi'an, China, between 2016 and 2022. Kaplan-Meier analysis was used to examine LTFU and death time for rapid and delayed ART initiation. Moreover, multivariate Cox regression was employed to evaluate the correlation between rapid ART initiation and LTFU/mortality, while logistic regression was utilized to assess the association between rapid ART and 12-month virologic failure.

Results: Of the 6992 participants, 770 (11.0%) initiated ART ≤7 days postdiagnosis. The percent of ART initiations in the first week postdiagnosis quadrupled from 4.2% in 2016 to 19.7% in 2022. The LTFU rate for rapid ART initiators was comparable to that in the 8-29- (P = 0.132) and ≥30-day groups (P = 0.432). Mortality was notably decreased in the rapid ART group (0.0%) than in the 8-29- (1.5%) and ≥30-day groups (2.2%). The rapid ART initiators demonstrated lower odds of developing virologic failure compared with delayed ART initiators (aOR: 0.50; 95% CI: 0.26-0.89; P = 0.028; ≤7 days versus ≥30 days).

Conclusions: Under China's treat-all policy, rapid ART initiation showed equivalent LTFU but lower mortality and virologic failure. Chinese HIV patients may benefit from rapidly ART, but they require more intensive, tailored counseling to remain in treatment.

Background: The gut-brain axis is increasingly recognized as a key regulator of neurological health, with microbial metabolites influencing neurotransmission, synaptic plasticity, and neuroinflammation. Probiotics such as Lactobacillus rhamnosus GG and Bifidobacterium longum 1714 have been associated with neuroactive effects, yet the molecular mechanisms linking microbial genomic potential to host neuronal responses remain poorly defined.

Objective: This study aimed to integrate microbial genomics, neurotranscriptomics, and in vitro validation to unravel the neuromodulatory effects of L. rhamnosus GG and B. longum 1714.

Methods: Whole-genome functional annotation, metabolic pathway prediction, and biosynthetic gene cluster analysis were performed to identify neuroactive potential. Neuronal RNA-seq datasets (n = 3 biological replicates per condition) were analyzed using differential expression, WGCNA, and GSEA to capture transcriptomic responses. Multi-omics integration (CCA, DIABLO, SPIEC-EASI) linked microbial pathways with neuronal gene modules. In vitro assays using SH-SY5Y and iPSC-derived neurons validated predictions through measurements of cell viability, oxidative stress, neurotransmitter release (ELISA), qPCR of synaptic and inflammatory genes, and extracellular vesicle characterization including EV transcript profiling.

Results: Genomic analysis revealed that L. rhamnosus GG was enriched in γ-aminobutyric acid (GABA) and SCFA pathways, while B. longum 1714 carried tryptophan-indole metabolism genes. Transcriptomic profiling demonstrated upregulation of synaptic genes (BDNF, SYN1), showed upregulation of synaptic genes (BDNF, SYN1), serotonergic transporters (SLC6A4, TPH2), and suppression of inflammatory mediators (IL-6, TNF-α). Integration analyses identified two major subnetworks: a "neurotransmission module" driven by L. rhamnosus GG and a "serotonin-immune module" driven by B. longum 1714. In vitro validation confirmed increased GABA (1.7-fold) and serotonin (1.5-fold) release, reduced ROS (-18 to -22%), and EV transcript enrichment for synaptic and anti-inflammatory markers.

Conclusion: This multi-omics study demonstrates mechanistic evidence that probiotics exert complementary neuromodulatory effects: L. rhamnosus GG primarily enhances GABAergic and SCFA-mediated synaptic pathways, whereas B. longum 1714 regulates the tryptophan-serotonin-immune axis. Together, these findings support the therapeutic potential of precision probiotics for neurological health and establish a systems-level framework for probing host-microbe interactions.