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Gene regulation in Bacteroides fragilis: adaptive control in a dynamic host environment
No full textBacteroides fragilis occupies a dynamic position within the human gut.
Though it comprises a relatively minor fraction of the gut microbiota, it is disproportionately enriched at extraintestinal sites of infection. This ability to survive in contrasting host environments pivots on a regulatory framework that is both modular and highly plastic. Rather than deploying a suite of hierarchical global regulators, B. fragilis
employs numerous operon-embedded transcriptional switches, including site-specific
DNA inversions, phase-variable epigenetic systems, extracytoplasmic function sigma/
anti-sigma factor pairs, and hybrid two-component systems. These networks are
further complemented by cis-regulatory elongation checkpoints and post-transcriptional control by small RNAs. This review explores the full spectrum of these regulatory mechanisms, highlighting how they facilitate niche adaptation, surface variation,
immune evasion, and metabolic prioritization. It also explores intraspecies variation
focusing on glycan metabolism, antibiotic resistance, and virulence. Additionally, it
outlines recombination-driven regulation, alongside extracytoplasmic function sigma
factor diversification, flexible promoter architecture, and elongation checkpoints, each
contributing to the evolution of transcriptional control in B. fragilis. Finally, it outlines
unanswered questions, including the largely unexplored sRNA regulon, the coordination
of DNA inversions, elongation control, and phase-variable methylation, and proposes
experimental strategies to investigate the integration of these regulatory systems during
environmental transitions. Taken together, B. fragilis emerges as a model bacterium
for studying decentralized gene regulation in complex microbial ecosystems, with
implications for both microbial ecology and therapeutic targeting of the gut microbiota
The TRAPPC8/TRS85 subunit of the Arabidopsis TRAPPIII tethering complex regulates endoplasmic reticulum function and autophagy
Full text linkTransport protein particle (TRAPP) tethering complexes are known for their function as Rab GTPase exchange factors. Two versions of the complex are considered functionally separate: TRAPPII, an activator of the Rab11 family (RabA in plants) GTPases that function in post-Golgi sorting, and TRAPPIII, activating Rab1 family (RabD in plants) members that regulate endoplasmic reticulum (ER)-to-Golgi trafficking and autophagy. In Arabidopsis (Arabidopsis ahaliana), the TRAPPIII complex has been identified and its subunit composition established, but little is known about its functions. Here, we found that binary subunit interactions of the plant TRAPPIII complex are analogous to those of metazoan TRAPPIII, with the 2 large subunits TRAPPC8 and TRAPPC11 linking the TRAPP core and the small C12 to C13 dimer. To gain insight into the functions of TRAPPIII in plants, we characterized 2 A. thaliana trappc8 mutants. These mutants display abnormalities in plant morphology, particularly in flower and seed development. They also exhibit autophagic defects, a constitutive ER stress response, and elevated levels of the ER lipid dolichol (Dol), which is an indispensable cofactor in protein glycosylation. These results indicate that plant TRAPPC8 is involved in multiple cellular trafficking events and suggest a link between ER stress responses and Dol levels
BAF60/SWP73 subunits define subclasses of SWI/SNF chromatin remodelling complexes in Arabidopsis
Full text linkCRISPRi screen identifies FprB as a synergistic target for gallium therapy in Pseudomonas aeruginosa
Full text linkWith the rise of antibiotic-resistant bacteria, non-antibiotic therapies like gallium gain increasing attention. Intravenous gallium nitrate is under Phase II clinical trials to treat chronic Pseudomonas aeruginosa infections in cystic fibrosis patients. However, its clinical efficacy is constrained by the achievable peak concentration in human tissue. To address this limitation, we apply a genome-wide CRISPR interference approach (CRISPRi-seq) to identify potential synergistic targets with gallium. We classify the essential genes by response time and growth reduction, pinpointing the most vulnerable therapeutic targets in this species. In addition, we identify a highly conserved gene, fprB, encoding a ferredoxin-NADP⁺ reductase, whose deletion sensitizes P. aeruginosa to gallium, lowering its MIC by 32-fold and shifting mode of action from bacteriostatic to bactericidal. Further investigation reveals that FprB plays a critical role in modulating oxidative stress induced by gallium, via control of iron homeostasis and reactive oxygen species accumulation. Deleting fprB enhances gallium’s efficacy against biofilm formation and improves outcomes in a murine lung infection model of P. aeruginosa, suggesting FprB is a promising drug target in combination with gallium. Overall, our data show CRISPRi-seq as a powerful tool for systematic genetic analysis of P. aeruginosa, advancing the identification of novel therapeutic targets
Genetic diversity of Bartonella spp. in rodents and fleas from Poland
Full text linkBartonella spp. are parasites of mammalian erythrocytes and endothelial cells, and are transmitted by blood-feeding arthropod ectoparasites, including fleas. This study aimed to: (i) identify the main flea species responsible for Bartonella transmission and the specific Bartonella species they carry, (ii) evaluate how host-related factors influence the prevalence of Bartonella, (iii) examine the genetic diversity of Bartonella from different flea species and mammalian hosts, including rodents and European moles, and (iv) determine the haplotypes of Bartonella derived from rodents. Blood samples were collected from seven rodent species and two European moles in Poland (n = 994), and fleas were collected from rodents (n = 833). Bartonella spp. were identified and genotyped through rpoB and gltA genes. Phylogenetic analysis revealed two dominant Bartonella spp. in rodents and fleas: B. grahamii and B. taylorii. Moreover, 17 haplotypes of B. taylorii and 9 of B. grahamii were identified. The sequences of Bartonella sp. from T. europaea clustered in a unique separate group, possibly indicating a novel species. The study confirmed fleas as vectors of Bartonella transmission in rodents and highlighted the significant genetic diversity of Bartonella spp. in both fleas and rodents
Analysis of NUDIX enzymes across fungi reveals previously unrecognized diversity
Full text linkBackground
The NUDIX superfamily encompasses highly diverse enzymes involved in a plethora of biological functions such as mRNA metabolism, DNA repair, and lipid peroxidation. These hydrolases are found in all domains of life and show surprising versatility in terms of the substrates that they process. The knowledge about the diversity of fungal NUDIX proteins is fragmentary, being largely limited to a small number of characterized enzymes from yeasts. To address this knowledge gap systematically, we performed a detailed analysis of the NUDIX hydrolases across 183 fungal proteomes.
Results
Members of six of the known NUDIX families were present in fungi being particularly abundant in Glomeromycota. Phylogenetic analysis and sequence clustering grouped fungal NUDIX enzymes in 25 subfamilies, 13 of which did not cluster with previously known enzymes. These 13 newly identified subfamilies all belong to the canonical NUDIX family, and structural comparison revealed a typical NUDIX fold with α-β-α sandwich structure. Molecular docking suggested Ap3A and Ap4A as substrates with the highest binding affinity, but their possible cellular roles remain unclear. We also found evidence of expression of most of the genes that encode these enzymes, suggesting physiological relevance.
Conclusions
Our analysis offers a comprehensive perspective on the structural and sequence relationships of the NUDIX superfamily across fungi with potential to guide experimental characterization of their biological function
Prebiotic potential of spent brewery grain – In vitro study
Full text linkSpent brewery grain (SBG) is a by-product of the brewery industry. The study aimed to investigate the prebiotic potential of SBG. The chemical composition and fermentation capacity of SBG were checked. The gut microbiota response to SBG was assessed in two in vitro models (batch fermentation and dynamic system). Substances with prebiotic properties, including arabinoxylans (16.7 g/100 g) and polyphenols (49.1 mg/100 g), were identified in SBG. Suitable growth and fermentation by probiotic bacteria were observed. The modulatory effect of gut microbiota depends on the in vitro system used. In batch fermentation, there was no stimulation of Bifidobacterium or lactic acid bacteria (LAB), but short-chain fatty acid (SCFA) and branched short-chain fatty acids (BCFA) synthesis increased. In dynamic, SBG exhibited a moderate bifidogenic effect, promoting Akkermansia and LAB growth while reducing Bacteroides and Escherichia-Shigella. SCFA stabilisation and reduction of BCFA content were noted. Moderate prebiotic effects were observed
Ribosomes translocation into the spore of Bacillus subtilis is highly organised and requires peptidoglycan rearrangements
Full text linkIn the spore-forming bacterium Bacillus subtilis transcription and translation are uncoupled and the translational machinery is located at the cell poles. During sporulation, the cell undergoes morphological changes including asymmetric division and chromosome translocation into the forespore. However, the fate of translational machinery during sporulation has not been described. Here, using microscopy and mass spectrometry, we show the localisation of ribosomes during sporulation in wild type and mutant Bacillus subtilis. We demonstrate that ribosomes are associated with the asymmetric septum, a functionally important organelle in the cell's developmental control, and that SpoIIDMP-driven peptidoglycan rearrangement is crucial for ribosomes packing into the forespore. We also show that the SpoIIIA-SpoIIQ 'feeding-tube' channel is not required for ribosome translocation. Our results demonstrate that translation and translational machinery are temporally and spatially organised in B. subtilis during sporulation and that the forespore 'inherits' ribosomes from the mother cell. We propose that the movement of ribosomes in the cell may be mediated by the bacterial homologs of cytoskeletal proteins and that the cues for asymmetric division localisation may be translation-dependent. We anticipate our findings to elicit more sophisticated structural and mechanistic studies of ribosome organisation during bacterial cell development
Integrated Transcriptomic and Proteomic Analysis of Omentin-1 Effects on Primary Anterior Pituitary Cells From Different Pig Breeds: An In Vitro Study
Full text linkOmentin-1 (OMNT1) is a metabolically active adipokine implicated in endocrine regulation; however, its role in the anterior pituitary (AP) remains unknown. We hypothesized that OMNT1 modulates the endocrine function of AP cells through gene- and protein-level mechanisms, with effects depending on the animal's metabolic background. To investigate this hypothesis, AP cells isolated from two pig breeds with distinct metabolic profiles, Large White (LW; normal weight) and Meishan (MS; genetically obese), were treated with OMNT1. Transcriptomic and proteomic analyses were performed alongside assessments of hormone expression and secretion. Transcriptomic profiling revealed 13 310 and 13 272 expressed genes in LW and MS pigs, respectively. Differentially expressed gene (DEG) analysis revealed 655 DEGs in LW pigs and 420 in MS pigs. Integrated transcriptomic and proteomic analyses revealed that OMNT1 modulates pathways involved in cellular signaling, cytoskeleton dynamics, responses to stimuli, intracellular protein transport, and post-translational modifications. We further examined the mRNA expression and secretion of tropic hormones (GH, PRL, TSH, ACTH, LH, and FSH) and selected adipokines (adiponectin, leptin, chemerin, apelin, visfatin, resistin, and vaspin), along with their specific receptors. OMNT1 increased LH secretion and decreased FSH levels in a breed-dependent manner. Additionally, in MS pigs, OMNT1 reduced adiponectin and increased leptin secretion. These findings highlight the role of OMNT1 as a key modulator of pituitary endocrine activity, integrating metabolic signals through breed-specific molecular responses at the transcriptional, proteomic, and functional levels
Predicting the S. cerevisiae Gene Expression Score by a Machine Learning Classifier
Full text linkThe topic of this work is gene expression and its score according to various factors analyzed globally using machine learning techniques. The expression score (ES) of genes characterizes their activity and, thus, their importance for cellular processes. This may depend on many different factors (attributes). To find the most important classifier, a machine learning classifier (random forest) was selected, trained, and optimized on the Waikato Environment for Knowledge Analysis WEKA platform, resulting in the most accurate attribute-dependent prediction of the ES of Saccharomyces cerevisiae genes. In this way, data from the Saccharomyces Genome Database (SGD), presenting ES values corresponding to a wide spectrum of attributes, were used, revised, classified, and balanced, and the significance of the considered attributes was evaluated. In this way, the novel random forest model indicates the most important attributes determining classes of low, moderate, and high ES. They cover both the experimental conditions and the genetic, physical, statistical, and logistic features. During validation, the obtained model could classify the instances of a primary unknown test set with a correctness of 84.1%