Frontiers in Cellular and Infection Microbiology最新文献

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.

Background: Human respiratory syncytial virus (HRSV) is a leading cause of acute respiratory infections in children. COVID-19 NPIs significantly suppressed HRSV transmission. This study analyzed six-year epidemiological dynamics of pediatric HRSV infections in Henan Province, China, focusing on NPI suppression effects, the 2023 resurgence, and "Immune debt" impact.

Methods: We retrospectively collected respiratory specimens from 80,920 children with acute respiratory diseases at Henan Children's Hospital (2019-2024). HRSV was detected using RT-qPCR. Positivity rates were analyzed by year, season, and age group.

Results: During 2019-2024, HRSV positivity fluctuated markedly: 14.65% (2019), 16.34% (2021), 3.27% (2022 under strict NPIs), 21.47% (2023 post-NPIs), and 6.80% (2024). Interrupted time-series analysis indicated that NPI lifting in 2023 was associated with a significant surge in infection risk (OR = 668.77, 95% CI: 47.03-9509.28). Seasonal patterns shifted substantially, with the characteristic winter peak replaced by an off-season spring outbreak in April 2023 (57.41%). Multivariable logistic regression identified age as the strongest predictor, with infants <1 year having the highest risk (aOR = 9.02, 95% CI: 8.31-9.79) and a 4.91-fold higher positivity rate than school-aged children (22.98% vs. 4.68%; 95% CI: 4.59-5.25; P < 0.001).

Conclusions: NPIs dramatically affected HRSV epidemiology. The intense post-suppression rebound strongly supports the "Immune debt" theory-accumulation of susceptible children driving resurgence. Establishing year-round, multi-pathogen surveillance systems is crucial for post-pandemic public health challenges.

Background: Mycoplasma bovis mastitis is an important disease of dairy cows; however, there are no commercial M. bovis vaccines and antimicrobial resistance is increasing. Furthermore, M. bovis lacks a cell wall and relies on host-derived cholesterol for survival and growth.

Methods: We evaluated effects of fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist, on M. bovis infection, using both bovine mammary epithelial cells and a murine mastitis model. In vitro analyses assessed autophagy, nuclear Transcription Factor EB (TFEB) and Transcription Factor E3 (TFE3) translocation, cholesterol metabolism, and bacterial localization, whereas in vivo evaluations included inflammatory responses, lysosomal/autophagy protein expression, cholesterol content, and bacterial burden.

Results: Fenofibrate enhanced autophagic flux via upregulation of LC3B and LAMP2, promoted nuclear translocation of TFEB and TFE3, and reduced intracellular cholesterol by repressing 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase (HMGCR) and Sterol Regulatory Element-Binding Transcription Factor 2 (SREBF2) while increasing Acetyl-Coenzyme A Acetyltransferase 1 (ACAT1) expression. Based on confocal imaging, fenofibrate disrupted co-localization between M. bovis and free cholesterol while enhancing its uptake by autophagosomes. In a murine mastitis model, fenofibrate alleviated inflammatory cell infiltration and cytokine release, restored lysosomal and autophagy protein expression, reduced cholesterol content, and significantly lowered bacterial burden.

Conclusion: Fenofibrate enhanced defense capability of mammary epithelial cells against M. bovis infection through a dual mechanism-promoting autophagy and regulating cholesterol homeostasis-thereby reducing bacterial survival and protecting tissues from damage. This discovery provides a novel strategy for prevention and treatment of M. bovis infection, warranting further investigation in bovine models to assess pharmacokinetics, dosage, and clinical efficacy.

Background: The emergence of azole-resistant strains of Aspergillus fumigatus presents a significant challenge in clinical and settings, necessitating the development of alternative antifungal strategies. Chitosan-silver nanocomposites (Chi-AgNPs) have emerged as promising candidates due to their dual antimicrobial mechanisms and enhanced physicochemical properties.

Objectives: This study aimed to evaluate the synthesis, characterization, antifungal properties, and low toxicity in an invertebrate model of Chi-AgNPs compared with those of chitosan and silver nanoparticles (AgNPs) alone, particularly against azole-resistant A. fumigatus.

Methods: Chi-AgNPs were synthesized via a chemical reduction method and characterized using particle size analysis, ultraviolet-visible (UV-Vis) spectroscopy, Fourier transform infrared (FTIR), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Antifungal efficacy was assessed through minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), microbial growth curves, and in vivo tests using Galleria mellonella larvae. Reactive oxygen species (ROS) generation and fungal cell wall deformation were analyzed to explore the antifungal mechanism.

Results: Compared with chitosan and AgNPs alone, Chi-AgNPs exhibited superior physicochemical properties, with smaller and more uniform particle sizes (average: 212.5 nm) and improved dispersion stability based on immediate characterization data. The MIC and MFC of Chi-AgNPs (8-16 μg/mL and 128 μg/mL, respectively) were significantly lower than those of chitosan and AgNPs (128 μg/mL and >256 μg/mL, respectively). Compared with AgNPs, Chi-AgNPs induced higher ROS levels (p < 0.05) and were associated with more severe fungal cell wall damage. In vivo, the Chi-AgNPs-treated fungus-infected group presented the lowest mortality in G. mellonella larvae (p < 0.05), demonstrating superior antifungal activity and low toxicity in an invertebrate model.

Conclusions: This study highlights the potential of Chi-AgNPs as promising alternatives to combat azole-resistant fungal infections. These findings provide a foundation for further development of Chi-AgNPs as novel antifungal agents with broad applicability.

Objective: The clinical characteristics of Klebsiella pneumoniae liver abscess (KPLA) and Klebsiella pneumoniae bloodstream infection (KP-BSI) are often reported, while the risk factors for KPLA combined with KP bloodstream infection (KPLA/KP-BSI) among KPLA are largely unknown. Therefore, this study aimed to investigate the clinical characteristics, risk factors, and outcomes of patients with KPLA complicated by KP-BSI.

Methods: A retrospective study from May 2013 to October 2020 at a tertiary hospital compared KPLA patients with and without KP-BSI, analyzing clinical data.

Results: Among all liver abscess cases during the study period, Klebsiella pneumoniae was the most common pathogen, accounting for 76.0% of isolates. Of 233 KPLA patients, 68.7% were male with a median age of 60.5 years. KPLA/KP-BSI occurred in 27.9%. Patients with KPLA/KP-BSI had higher male prevalence, abdominal surgery history, and higher APACHE II, SOFA, and CCI scores (p<0.05). Logistic regression showed SOFA score ≥ 2 (aOR 3.326) was a risk factor for KPLA/KP-BSI, while liver abscess size > 10 cm reduced the risk (aOR 0.144). KPLA/KP-BSI was associated with worse outcomes, including higher septic shock, acute kidney injury, transfusion rates, organ dysfunction, pneumonia, longer hospital stays, and higher mortality (all p<0.05).

Conclusion: Nearly one-third of patients with KPLA have concurrent KP-BSI. A SOFA score ≥2 is an independent risk factor, whereas abscess diameter >10 cm is protective. KPLA/KP-BSI is associated with significantly higher rates of septic shock, organ dysfunction, and in-hospital mortality, warranting heightened clinical attention.

Carbapenem-resistant Enterobacterales bloodstream infection (CRE-BSI) represents a major and urgent challenge to global public health. Some patients with CRE-BSI have a greater risk for poor clinical outcomes, thus identifying risk factors for CRE-BSI is required to determine the most at-risk populations. Here, we investigated risk factors for CRE-BSI by conducting a retrospective case-case-control study at Tianjin Medical University General Hospital, between 2017 and 2024. A total of 144 patients with CRE-BSI were enrolled in this case-case-control study. Each case was matched simultaneously to a patient with carbapenem-susceptible Enterobacterales BSI (CSE-BSI) and a control patient with non-Enterobacterales bacteremia in a 1:1:1 ratio. This design facilitated the analysis of risk factors and a comparison of 30-day survival outcomes among groups. Multivariable logistic regression identified distinct risk factor profiles for different infections. Surgical history emerged as an independent risk factor for Enterobacterales-BSI. Independent risk factors for CRE-BSI encompassed prior exposure to third-generation cephalosporins (OR = 1.94), carbapenems (OR = 3.45), quinolones (OR = 2.54), and glucocorticoids (OR = 2.55), in addition to a history of surgery (OR = 2.44) and gastric tube insertion (OR = 2.45). In-hospital mortality for CRE-BSI reached 52.8%. Furthermore, arterial catheter use (OR = 2.50) was identified as an independent risk factor for in-hospital mortality in patients with CRE-BSI. Cox proportional hazards modeling revealed several independent predicators of 30-day mortality: patient group (HR = 1.37; 95% CI, 1.01-1.86; p = 0.04), age ≥ 65 years (HR = 0.43; 95% CI, 0.20-0.93; p = 0.03), respiratory diseases (HR = 3.17; 95% CI, 1.54-6.51; p = 0.002), and digestive system diseases (HR = 1.79; 95% CI, 1.03-3.10; p = 0.04). Thus, a comprehensive evaluation of underlying diseases, antibiotic usage, and invasive procedures is required to reduce CRE-BSI-associated mortality. Given the notable morbidity and mortality, as well as constrained therapeutic options, associated with CRE-BSI, identifying risk factors for CRE-BSI is urgently required for effective disease prevention and to develop novel therapeutic strategies.

[This corrects the article DOI: 10.3389/fcimb.2025.1678489.].

Background: The emergence of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae presents significant challenges in treating infections caused by these pathogens. This multi-center retrospective study investigated the prevalence of OXA-1 and TEM-1 genes in ESBL-producing E. coli and K. pneumoniae, along with their association with piperacillin/tazobactam susceptibility and additional antimicrobial resistance genes.

Methods: Clinical isolates were collected from three institutions as part of routine patient care: Tripler Army Medical Center (TAMC) in Hawaii, Madigan Army Medical Center (MAMC) in Washington, and Brooke Army Medical Center (BAMC) in Southern Texas. A total of 416 isolates were analyzed through genome sequencing and CLSI-guided susceptibility testing.

Results: OXA-1 and TEM-1 β-lactamase enzymes were present in 20.9% (73/349) and 38.7% (135/349) of the E. coli isolates, respectively. Relative risk analysis of non-susceptibility to piperacillin/tazobactam across isolates from the three study sites revealed a highly significant association for OXA-1 (P < 0.001), whereas no significant associations were observed for TEM-1 (P = 0.424) or the combination of OXA-1 and TEM-1 (P = 0.082). When analyzed by institution, the relative risk of non-susceptibility to piperacillin/tazobactam remained highly significant for OXA-1 at TAMC and MAMC (P < 0.001 for both) but was not significant at BAMC (P = 0.21). OXA-1 and TEM-1-positive variants showed a significant association with genes conferring resistance to other antibiotics.

Conclusions: The OXA-1 gene plays a key role in resistance to piperacillin/tazobactam in ESBL-producing organisms, with geographic differences in non-susceptibility observed. Genetic profiling and localized data are crucial for optimizing antibiotic therapy and improving treatment outcomes.

Lichens are well known for producing unique secondary metabolites, some of which have been shown to exhibit medically relevant bioactivities, including antimicrobial effects. With the increasing prevalence of fungal infections and the growing resistance to commonly used antimycotics, there is an urgent need for new antifungal agents, especially for aged and/or immunocompromised individuals. In this study, we screened a collection of lichen-derived metabolites for antifungal properties in two medically relevant fungal pathogens, Candida albicans and Nakaseomyces glabratus. Several compounds exhibited inhibitory effects against planktonic cells and/or biofilm formation in at least one of these species. Notably, two related paraconic acids demonstrated the strongest activity against biofilms, structures that contribute significantly to antifungal resistance. Among them, lichesterinic acid was the most effective in disrupting pre-formed biofilms and preventing biofilm formation, key challenges in clinical mycology. Importantly, lichesterinic acid showed moderate tolerability in human cells. Furthermore, lichesterinic acid displayed antifungal efficacy in an in vivo model of fungal infection, supporting its potential for therapeutic development. These findings highlight lichen-derived metabolites, particularly paraconic acids, as promising candidates for new antifungal therapies targeting resistant and biofilm-associated fungal infections.