Frontiers in Microbiology最新文献

Malaria, a disease caused by protozoa of the genus Plasmodium, remains a major challenge for global public health. The persistence of disease transmission to the mosquito vector depends on the differentiation of asexual blood-stage parasites into gametocytes, a process known as gametocytogenesis. Interrupting this stage of the parasite's life cycle represents a critical strategy for malaria control and eventual eradication. This review aims to consolidate recent advances in the understanding of the complex molecular mechanisms regulating gametocytogenesis in Plasmodium, with a particular focus on P. falciparum. Sexual differentiation is modulated by various factors, including environmental stressors such as the depletion of lysophosphatidylcholine (LysoPC), and is orchestrated through a sophisticated regulatory network. At the transcriptional level, the AP2-G transcription factor functions as a master switch, whose expression is tightly regulated by epigenetic mechanisms, including histone H3K9 trimethylation (H3K9me3) as well as the activity of both heterochromatin protein 1 (HP1) and gametocyte development protein 1 (GDV1). Following commitment, post-transcriptional regulation plays a critical role in further differentiation, including transcript stabilization by RNA-binding proteins such as PfPuf1 and PfPuf2, along with epitranscriptomic modifications such as mRNA methylation (m⁵C and m⁶A), which modulate gene expression. A comprehensive understanding of these interconnected regulatory pathways is essential for the identification of novel therapeutic targets and the development of effective transmission-blocking vaccines.

Introduction: Straw return exerts a profound impact on soil fertility, with particularly critical implications for soil carbon (C) pools. Soil hydrolytic C-degrading extracellular enzyme activities (Hy-EEAs) play a central role in soil C cycling. However, the effects of straw return on Hy-EEAs, below-ground C dynamics, and the underlying regulatory mechanisms have not been fully elucidated.

Methods: In this study, we evaluated the effects of straw incorporation on Hy-EEAs and below-ground C, as well as their potential relationships, by synthesizing 211 observations from 68 published field studies worldwide.

Results: On average, straw return significantly enhanced Hy-EEAs by 25% but had no effect on β-xylosidase. Straw return significantly increased dissolved organic carbon, easily oxidizable carbon, light fraction organic carbon, particulate organic carbon, microbial biomass carbon, and soil organic carbon by 27, 24, 51, 34, 31, and 20%, respectively, compared to the no-straw-return treatment. The effect of straw return on Hy-EEAs decreased with increasing experiment duration (≥ 10 years). Straw return effects on Hy-EEAs increased with the incorporation of straw. The response ratios (lnR) of microbial biomass C content and soil organic carbon (SOC) storage to straw return were positively correlated with the lnR of Hy-EEAs; however, no clear relationships were found between the lnR of soil dissolved organic C (DOC), easily oxidizable C (EOC), light fraction organic C (LFOC), and particulate organic C (POC) and the lnR of Hy-EEAs.

Discussion: These results suggest that straw return stimulation of Hy-EEAs exhibited a key role in regulating below-ground C dynamics. Future biogeochemistry models could incorporate the observed relationships in this study between the soil C pool and Hy-EEAs, which can improve model predictions of C in soils under straw return in agricultural systems.

Introduction: Rice bacterial leaf blight, caused by Xanthomonas oryzae pv. oryzae (Xoo), is a highly destructive disease. Within the rice-Xoo pathosystem, Pantoea ananatis exhibits a dual role, functioning both as a pathogen and as a biocontrol agent, underscoring the need to clarify its speciffc functions for effective disease management.

Methods: Isolated strains ZJU1-ZJU18 were identified using multi-locus sequence analysis, core-genome phylogenomic analysis, and average nucleotide identity. The population density of Xoo in rice leaves was determined by plate counting and qPCR to evaluate the inhibitory effect of P. ananatis on its growth.

Results and discussion: The isolated strains ZJU1-ZJU18 were all identiffed as P. ananatis, and they exhibited plant growth-promoting traits, including phosphate solubilization, siderophore production, and indole-3-acetic acid synthesis. Furthermore, strains ZJU1-ZJU18 did not induce rice bacterial leaf blight symptoms under the experimental conditions, with the lesion inhibition rate against this disease ranging from 95.14 to 97.92%. Mechanistic investigations revealed that P. ananatis suppressed Xoo via nutrient competition, dominating co-culture systems (>90% relative abundance) and reducing Xoo colonization on rice leaves by 96.78-99.00%. Xoo infection enhanced P. ananatis colonization, likely by modifying the leaf microenvironment. Furthermore, the results of species composition analysis showed that P. ananatis could alter the structure and diversity of the microbial community in rice leaves and reduce the abundance of Xanthomonas species. The principal coordinate analysis indicated that P. ananatis had a more signiffcant impact on the microbial community composition than Xoo. This study found that P. ananatis may inhibit the pathogen Xoo through nutrient competition and reshape the microbial structure at the community level.

Introduction: The Qinghai-Tibet Plateau, an extreme high-altitude ecosystem, presents a unique model for studying host-microbe-environment coevolution under environmental stress. However, the role of resident wildlife, particularly non-migratory passerines, as reservoirs and vectors for cross-boundary antibiotic resistance gene (ARG) dissemination remains poorly understood.

Methods: Here, through metagenomic analysis of two endemic passerines (Pseudopodoces humilis and Pyrgilauda ruficollis) and their habitats.

Results: We reveal convergent adaptations in their gut microbiomes, dominated by Actinomycetota, Pseudomonadota and Bacillota. Functional enrichment in carbohydrate metabolism and genetic information processing underpins host energy optimization in extreme high-altitude environments. Critically, these birds constitute a major reservoir of ARGs, harboring 153 antibiotic resistance ontologies (AROs) with nearly universal resistance to clinical antibiotic classes. The core resistome-comprising glycopeptide (van clusters), fluoroquinolone, and tetracycline resistance genes-reflects anthropogenic contamination amplified by environmental persistence. Environmental transmission pathways were unequivocally demonstrated via 47 AROs shared between avian hosts and proximal matrices (soil/grass), coupled with livestock-derived antibiotic influx through excreta, establishing the plateau as a hotspot for resistance gene flux. Strikingly, "low-abundance-high-resistance" taxa (Pseudomonadota, Actinomycetota, and Bacillota; ≤30% abundance but >80% ARG contribution) drive resistome plasticity, potentially facilitated by horizontal gene transfer.

Discussion: Our findings redefine resident passerines as sentinels of ecosystem health and bridges for cross-boundary antimicrobial resistance (AMR) spread. Mitigating global AMR thus necessitates interdisciplinary strategies targeting environmental reservoirs (e.g., regulating livestock antibiotic use) and monitoring avian-mediated gene flow.

Background: Rabid animal bites are a medical emergency, requiring immediate post-exposure prophylaxis (PEP) to prevent human deaths. This study modeled geographical accessibility to health facilities stocking rabies vaccines and assessed the impact of optimizing vaccine placement within a rural Kenyan healthcare network.

Methods: We used geocoordinates of Kenyan health facilities from an open-access inventory and identified those stocking PEP in Makueni County. Using population distribution data and a travel time friction surface, we estimated travel times to all health facilities, including those stocking PEP. We assessed the proportion of the population within 30 min, 1, 1.5, 2, and >2 h of these facilities. We further used dog-bite data from contact-tracing studies (2017-2021) to estimate the shortest distance and travel time for patients accessing PEP.

Results: Two-thirds (66.6%) of the population lived within a 30-min walk to any health facility, but only 7.4% had similar access to a PEP facility. Using the non-motorized travel scenario, 66.6, 29.4, 3.5, 0.3, and 0.2% of the population were within 30 min, 1 h, 1.5 h, 2 h, and more than 2 h of walking time, respectively, to any health facility. Among 931 bite patients identified through contact tracing, 376 (40.4%) could reach any health facility within 10 min, while only 289 (35.4%) had similar access to a PEP facility. Additionally, 27 (2.9%) required over 60 min to reach any health facility, while 26 (3.2%) needed over 60 min specifically to access PEP. When considering motorized travel, the entire population was within 30 min of both any facility and a PEP facility.

Conclusion: Our findings demonstrate that increased geographic distance and longer travel times to health facilities substantially reduce accessibility to rabies PEP, particularly in rural settings where reliance on non-motorized travel is common. To our knowledge, this is the first study to provide quantitative, county-specific estimates of travel time impacts on PEP access in rural Kenya, filling a critical evidence gap for planning PEP distribution under Kenya's Stepwise Approach to Rabies Elimination (SARE). Optimizing the placement of PEP within existing healthcare networks can increase the proportion of the population able to reach services within recommended time thresholds. Expanding vaccine availability at strategically located facilities would therefore improve timely PEP to bite victims and support efforts to prevent human rabies deaths. These results highlight the importance of incorporating geographic accessibility analyses into planning for rabies elimination programs.

Aspergillus niger, an industrial filamentous fungus recognized as GRAS (Generally Recognized as Safe) and vital for food fermentation and enzyme production, has an optimal fermentation temperature around 30 °C; however, heat stress in industrial systems impairs its cellular viability and reduces target product synthesis efficiency. This review systematically summarizes the multi-level coordinated heat stress response mechanisms of A. niger by integrating existing research findings, revealing that the fungus copes with heat stress via cell membrane remodeling, rapid accumulation of compatible solutes, cAMP/PKA-mediated metabolic reprogramming, protein quality control, and activation of antioxidant defense systems. These mechanisms synergistically enhance A. niger's heat resistance, while current research still lacks data on early stress signaling events, complete PKA downstream regulatory networks, and multi-omics integration. The review's innovation lies in identifying potential adaptive strategies specific to eukaryotic filamentous fungi (e.g., non-classical membrane regulation) and providing a theoretical basis for improving A. niger's thermotolerance through metabolic engineering.

The aging society presents a growing challenge in the form of osteosarcopenia (OS). This syndrome is marked by the concomitant deterioration of bone (osteoporosis) and muscle (sarcopenia), and significantly elevates the risks of fractures, disability, and mortality. Despite its clinical relevance, the shared pathophysiology and effective interventions for OS remain elusive. Emerging evidence highlights the gut microbiota (GM) as a critical modulator of musculoskeletal health. This review integrates current evidence to delineate "gut-muscle-bone Axis" framework, summarizing current evidence on how GM dysbiosis may be involved in OS through multifaceted mechanisms, including intestinal barrier disruption, chronic inflammation, endocrine dysregulation, impaired nutrient absorption, and disrupted muscle-bone crosstalk. GM-derived metabolites, such as short-chain fatty acids (SCFAs), interact with immune, metabolic, and hormonal pathways to influence osteoblast/osteoclast activity and muscle protein synthesis. Furthermore, systemic inflammation triggered by GM imbalance exacerbates bone resorption and muscle atrophy. The axis also highlights bidirectional feedback between muscle and bone, mediated by myokines (e.g., irisin) and osteokines (e.g., osteocalcin), which synergistically regulate musculoskeletal homeostasis. Therapeutic strategies targeting GM modulation-such as dietary optimization (plant-based proteins, high-fiber diets), probiotics/prebiotics, exercise, and fecal microbiota transplantation (FMT)-suggest a potential capacity to modulate gut-muscle-bone interactions, which may be relevant to osteosarcopenia-related pathophysiological processes. This review proposes an integrative conceptual framework for understanding the pathogenesis of OS, synthesizing evidence primarily derived from osteoporosis and sarcopenia research, as well as animal and mechanistic studies. While direct clinical evidence in OS remains limited, emerging findings suggest that microbiota-centered strategies may hold potential for future preventive and therapeutic exploration.

Background: Autism Spectrum Disorder (ASD) is frequently accompanied by gastrointestinal (GI) comorbidities and gut microbiota dysbiosis. While the microbiota-gut-brain axis is implicated in ASD pathophysiology, the upstream host genetic factors that drive these specific microbial alterations remain poorly characterized.

Methods: To bridge this gap, we performed an integrated multi-omics analysis combining whole-exome sequencing, 16S rRNA gene sequencing, and plasma metabolomics in a cohort of children with ASD and typically developing controls.

Results: We confirmed that children with ASD exhibit significant gut microbial dysbiosis and metabolic perturbations, which correlated with GI symptom severity. Crucially, rare variant enrichment analysis identified a significant accumulation of deleterious variants in mucin biosynthesis pathways (specifically the MUC gene family), which are essential for intestinal mucus barrier integrity. Multi-omics integration revealed that these host genetic defects were associated with distinct shifts in the gut ecosystem, notably the depletion of beneficial butyrate-producing bacteria (e.g., Faecalibacterium) and the expansion of mucin-degrading taxa. This structural dysbiosis translated into functional metabolic impairments, particularly in lipid transport and short-chain fatty acid metabolism, which tracked with ASD severity.

Conclusion: Collectively, our data argue for a host-centric cascade where genetic vulnerabilities-specifically within the MUC pathway-compromise mucosal integrity, acting as a selective filter that fundamentally reshapes the gut microbiome. By pinpointing these variants as upstream drivers of gut-brain axis dysfunction, we move beyond simple association to identify concrete genetic targets-rare deleterious variants in the mucin (MUC) gene family-for future precision interventions in ASD.

Extended-spectrum β-lactamase (ESBL) producers, particularly Escherichia coli and Klebsiella pneumoniae, pose a growing One Health challenge influenced by seasonal variation. This study assessed seasonal impacts on ESBL prevalence among humans, animals, and farm environments. A total of 2,890 poultry samples, 864 samples from dairy cows (including 88 milk samples and 776 rectal swabs), 248 human fecal samples (118 farm workers and 130 hospitalized patients) and 583 environmental samples were collected from Fayoum governorate, across three seasons. The isolation data revealed significant seasonal impacts, particularly in dairy cows and environmental samples, with source-related differences evident within the same season. The phenotypic and genotypic ESBL- analysis of all isolates from different sources across seasons showed that ESBL-producing E. coli demonstrated comparable prevalence in summer (14.68%) and fall (15%) before declining in winter (7.5%), while K. pneumoniae showed the highest prevalence in winter (29.4%), with lower detection in summer (11.9%) and absence in fall. Significant seasonal differences were detected, with ESBL-producing E. coli prevalence varying across sources in the fall (p = 0.039) and ESBL-producing K. pneumoniae showing variation in poultry across seasons (p = 0.042). Environmental isolates exhibited fluctuating trends, highlighting the role of farm environments in ESBL persistence and dissemination. At the genetic level, blaSHV and blaCTX-M1 demonstrated seasonal variation, whereas blaTEM showed no variation. Heat-map and hierarchical clustering showed significant correlation among harboring ESBL-genes, particularly blaSHV and blaCTX-M1, and resistance profiles to β-lactams antibiotics, as well as to non-beta-lactam antibiotics. Additionally, source- and species-based seasonal effects were observed in the prevalence of E. coli, K. pneumoniae, and their associated ESBL traits. The results further demonstrated that genotypic resistance determinants (bla genes) are significantly linked to phenotypic resistance, especially to β-lactams, and also reflected multi-drug resistance patterns that indicate co-selection across unrelated antibiotic classes. These findings highlight the public health significance of ESBL-producing E. coli and K. pneumoniae, both as pathogens and as disseminators of multidrug resistance determinants, emphasizing the need for One Health surveillance. To the best of our knowledge, this is the first systematic and comprehensive investigation of ESBL prevalence across animal, human and environmental, over three distinct seasons.

In its natural soil habitat, B. subtilis regularly encounters fluctuating conditions that require adaptive survival strategies, including the production and secretion of antimicrobial compounds. One such compound, surfactin, play a central role in multicellular differentiation processes such as biofilm formation, swarming, and competence development. Competence and surfactin biosynthesis are transcriptionally co-regulated via the quorum sensing-mediated activation of the srfAABCD operon, which contains comS in a distinct open reading frame overlapping with srfAB. This study aimed at uncoupling competence from surfactin production by introducing targeted stop mutations in comS to selectively disrupt competence without affecting surfactin synthesis. For this, we introduced single nucleotide polymorphisms (SNPs) that preserved the srfAB codons, while simultaneously introducing a premature stop codon in comS. The effects on competence development were assessed using luciferase-based reporter assays monitoring the ComS-dependent expression of comK and comGA expression. Surfactin production was analyzed by mass spectrometry imaging and phenotypic assays examining the impact on multicellular behavior. Our findings demonstrate that the generated point mutations severely reduce competence gene expression, measured via P _comK and P _comGA activity, to levels comparable with a full comS deletion, while leaving multicellular behaviors such as biofilm and pellicle formation, as well as swarming and sliding motility, unaffected. Thus, ComS is specifically essential for competence development but dispensable for other surfactin-mediated multicellular processes and not involved in structuring biofilms. Taken together, our results demonstrate that it is possible to genetically decouple competence from other developmental pathways in B. subtilis.