Human giant GTPase GVIN1 forms an antimicrobial coatomer around the intracellular bacterial pathogen Burkholderia thailandensis
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ABSTRACT:
PROVIDER: PRJNA1217935 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR32193800_1.fastq.gz | Fastqsanger.gz | |||
| SRR32193800_2.fastq.gz | Fastqsanger.gz | |||
| SRR32193801_1.fastq.gz | Fastqsanger.gz | |||
| SRR32193801_2.fastq.gz | Fastqsanger.gz | |||
| SRR32193802_1.fastq.gz | Fastqsanger.gz |
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Project description:Several human pathogens exploit the kinetic forces generated by polymerizing actin to power their intracellular motility. Human cell-autonomous immune responses activated by the cytokine interferon-gamma (IFNγ) interfere with such microbial actin-based motility, yet the underlying molecular mechanisms are poorly defined. Here, we identify the IFNγ-inducible human giant GTPases GVIN1 as a novel host defense protein that blocks the bacterial pathogen Burkholderia thailandensis from high-jacking the host's actin polymerization machinery. We found that GVIN1 proteins form a coatomer around cytosolic bacteria and prevent Burkholderia from establishing force-generating actin comet tails. Coatomers formed by a second IFNγ-inducible GTPase, human guanylate binding protein 1 (GBP1), constitute a GVIN1-independent but mechanistically related anti-motility pathway. We show that coating with either GVIN1 or GBP1 displaces the Burkholderia outer membrane protein BimA, an actin nucleator that is essential for actin tail formation. Both GVIN1 and GBP1 coatomers require additional IFNγ-inducible co-factors to disrupt the membrane localization of BimA, demonstrating the existence of two parallel-acting IFNγ-inducible defense modules that evolved to target a virulence trait critical for the pathogenesis of numerous bacterial infectious agents.
2025-04-14 | GSE288527 | GEO
Project description:Innate immunity responds to pathogens by producing alarm signals and activating pathways that make host cells inhospitable for pathogen replication. The intracellular bacterium Burkholderia thailandensis invades the cytosol, hijacks host actin, and induces cell fusion to spread to adjacent cells, forming multinucleated giant cells (MNGCs) which promotes bacterial replication. We show that type I interferon (IFN) restricts macrophage MNGC formation during B. thailandensis infection. Guanylate-binding proteins (GBPs) expressed downstream of type I IFN were required to restrict MNGC formation through inhibition of Arp2/3-dependent actin motility during infection. GTPase activity and the CAAX prenylation domain were required for GBP2 recruitment to B. thailandensis, which restricted bacterial actin polymerization required for MNGC formation. Consistent with in vitro macrophages, Gbp2-/- Gbp5-/-, GbpChr3-KO mice were more susceptible to intranasal infection with B. thailandensis than wildtype mice. Our findings reveal that IFN and GBPs play a critical role in restricting cell-cell fusion during infection
2021-08-23 | GSE143936 | GEO
Project description:Total transcript amplification (TTA) from single eukaryotic cells for transcriptome analysis is established, but TTA from a single prokaryotic cell presents additional challenges with much less starting material and lack of poly(A)-tails. We described, here, a novel method for single bacterium TTA, using a Burkholderia thailandensis model exposed to subinhibitory concentration of the antibacterial agent, glyphosate. Utilizing B. thialandensis microarray to assess the TTA method showed little gene bias (< 2 fold-change) and absence (~5-6%) when compared to the larger scale non-amplified RNA samples. B. thailandensis genes important to possibly recuperate and balance the intracellular amino acid pool were induced (or repressed) by the aromatic amino acid biosynthesis inhibitor, glyphosate. We validated our single-cell microarray data at the multi-cells and single-cell levels with lacZ and gfp reporter-gene fusions, respectively. This novel method will rejuvenate and expand the prokaryotic transcriptomic field. Two identical cultures of B. thailandensis wildtype strain E264 were grown in 1x M9 minimal medium supplemented with 1% Brij-58 and 20 mM glucose (MG) to mid-log phase. One culture was induced by final concentration of 0.01% (w/v) glyphosate for 30 minutes. Total RNA was then purified from B. thailandensis uninduced and induced samples, converted to cDNA and hybridized onto B. thailandensis 70mer triplicate array
2010-08-05 | E-GEOD-23419 | biostudies-arrayexpress
Project description:Burkholderia thailandensis is a soil-dwelling bacterium that shares many metabolic pathways with the ecologically similar, but evolutionarily distant, Pseudomonas aeruginosa. Among the diverse nutrients it can utilize is choline, which can be converted into the osmoprotectant glycine betaine and further catabolized as a source of carbon and nitrogen, similar to P. aeruginosa. Orthologs of genes in the choline catabolic pathway in these two bacteria showed distinct differences in gene arrangement as well as an additional orthologous transcriptional regulator in B. thailandensis. In this study, we showed that multiple glutamine amidotransferase1 (GATase1)-containing AraC-family transcription regulators (GATRs) are involved in regulation of the B. thailandensis choline catabolic pathway (gbdR1, gbdR2, souR). Using genetic analyses and sequencing the transcriptome in the presence and absence of choline, we identified the likely regulons of gbdR1 (BTH_II1869) and gbdR2 (BTH_II0968). We also identified a functional ortholog for P. aeruginosa souR, a GATR that regulates the metabolism of sarcosine to glycine. GbdR1 is absolutely required for expression of the choline catabolic locus, similar to P. aeruginosa GbdR, while GbdR2 is important to increase expression of the catabolic locus. Additionally, the B. thailandensis SouR ortholog (BTH_II0994) is required for catabolism of choline and its metabolites as carbon sources, whereas in P. aeruginosa, SouR function can by bypassed by GbdR. The strategy employed by B. thailandensis represents a distinct regulatory solution to control choline catabolism and thus provides both an evolutionary counterpoint and an experimental system to compare the acquisition and regulation of this pathway during environmental growth and infection.
2016-07-12 | GSE81652 | GEO
Project description:Introduction. Burkholderia thailandensis is a clinically rare opportunistic pathogen in the genus Burkholderia, and the genomic features and virulence characteristics of B. thailandensis strains that cause human infection remain unclear.Gap Statement. B. thailandensis strains with different virulence induce different host innate immune responses in vitro.Aim. This work aimed to understand the sequence diversity, phylogenetic relationship, and virulence of B. thailandensis BPM causing human infection.Methodology. The comparative molecular and genomic analyses, and mouse infection studies were applied to analyse the virulence and genomic features of B. thailandensis BPM originating from China.Results. The whole genome sequence analysis showed that the genomes of BPM and other avirulent B. thailandensis strains were broadly similar, comprising two highly syntenic chromosomes with comparable numbers of coding regions (CDs), protein family distributions, and horizontally acquired genomic islands. By examining species-specific genomic regions, we obtained molecular explanations for previously known differences in virulence and discovered the potential specific virulence-associated genes of BPM, which likely work together to confer the virulence of BPM. Significantly reduced LD50 and survival rates during mouse infection experiments were found in BPM compared to the avirulent B. thailandensis E264 (BtE264).Conclusion. Taken together, the results of this study provide basic information on the genomic features and virulence characteristics of the virulent B. thailandensis strain BPM, which is helpful for understanding its evolution as it relates to pathogenesis and environmental adaptability.
2021-02-15 | GSE147369 | GEO
Project description:Total transcript amplification (TTA) from single eukaryotic cells for transcriptome analysis is established, but TTA from a single prokaryotic cell presents additional challenges with much less starting material and lack of poly(A)-tails. We described, here, a novel method for single bacterium TTA, using a Burkholderia thailandensis model exposed to subinhibitory concentration of the antibacterial agent, glyphosate. Utilizing B. thialandensis microarray to assess the TTA method showed little gene bias (< 2 fold-change) and absence (~5-6%) when compared to the larger scale non-amplified RNA samples. B. thailandensis genes important to possibly recuperate and balance the intracellular amino acid pool were induced (or repressed) by the aromatic amino acid biosynthesis inhibitor, glyphosate. We validated our single-cell microarray data at the multi-cells and single-cell levels with lacZ and gfp reporter-gene fusions, respectively. This novel method will rejuvenate and expand the prokaryotic transcriptomic field.
2010-08-05 | GSE23419 | GEO
Project description:Burkholderia thailandensis is closely related to highly pathogenic Burkholderia species, and it is an excellent surrogate as it rarely causes disease in humans. Understanding the complex molecular mechanisms that characterize the transition of B. thailandensis from exponential to stationary phases is critical to understanding bacterial responses to stress or nutrient limitation. We present here an integrated transcriptomic and proteomic analysis to profile gene and protein expression changes during entry into stationary phase. We identified 928 differentially expressed genes (DEGs) and 832 differentially expressed proteins (DEPs), highlighting significant transcriptional and translational reprogramming. Genes encoding proteins involved in benzoate degradation and O-antigen nucleotide sugar biosynthesis were among the most highly upregulated in stationary phase, whereas processes such as nitrogen metabolism, translation, and flagellar biosynthesis were downregulated. At the proteome level, proteins related to fatty acid degradation and butanoate metabolism accumulated along with proteins involved in synthesis of secondary metabolites. Markedly downregulated proteins included ribosomal proteins and translation factors as well as the house-keeping iron-sulfur biogenesis proteins. A protein-protein interaction (PPI) network analysis identified clusters involved in processes such as fatty acid metabolism and amino acid degradation. Surprisingly, the RpoS sigma factor, which has been shown to accumulate in stationary phase in several bacterial species, was not significantly increased in B. thailandensis during stationary phase. These findings offer comprehensive insights into B. thailandensis adaptive strategies and provide a foundation for developing interventions against pathogenic Burkholderia species.
2025-07-13 | GSE279483 | GEO
Project description:Gracilibacillus thailandensis overview
| PRJNA587814 | ENA