Global transcriptome analysis of B. burgdorferi during adherence and invasion of human neuroglial cells
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PROVIDER: PRJNA101141 | ENA |
REPOSITORIES: ENA
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Project description:As adherence and entry of a pathogen into a host cell are two key components to an infection, identifying the molecular mechanisms responsible for cellular association will provide a better understanding of a microbe’s ability for pathogenesis. We previously established an in vitro model for B. burgdorferi invasion of human neuroglial cells. To expand on our earlier study, we performed B. burgdorferi whole-genome expression analysis following a 20-hour infection of human neuroglial cells to identify borrelial genes that were differentially regulated during cellular attachment and invasion as compared with cultured Borrelia in cell-free medium. This study identifies several regulated genes, the products of which may be important mediators for cellular pathogenesis. Keywords: in-vitro H4 neuroglial cells infected with B. burgdorferi
2008-06-20 | GSE8219 | GEO
Project description:As adherence and entry of a pathogen into a host cell are two key components to an infection, identifying the molecular mechanisms responsible for cellular association will provide a better understanding of a microbeâs ability for pathogenesis. We previously established an in vitro model for B. burgdorferi invasion of human neuroglial cells. To expand on our earlier study, we performed B. burgdorferi whole-genome expression analysis following a 20-hour infection of human neuroglial cells to identify borrelial genes that were differentially regulated during cellular attachment and invasion as compared with cultured Borrelia in cell-free medium. This study identifies several regulated genes, the products of which may be important mediators for cellular pathogenesis. Keywords: in-vitro H4 neuroglial cells infected with B. burgdorferi A 20-hour incubation was performed, and this time point included B. burgdorferi that were both intra- and extra-cellularly localized to the H4 cells (Livengood and Gilmore, 2006). After B. burgdorferi infection of these cells, the total cellular RNA preparation (including H4 RNA, and Borrelia RNA) was enriched for prokaryotic RNA, which concentrated the bacterial message, but did not completely eliminate the eukaryotic RNA (data not shown). Therefore, as a control in our arrays, eukaryotic RNA from the human H4 cells was also purified and hybridized to the array. To control for Borrelia cell-free gene expression, the data from the experimental conditions (B. burgdorferi infected human cells) was normalized to borrelial expression following growth in BSK and a 20 hour incubation in DMEM tissue culture media. As with the experimental samples, both controls were assayed in triplicate.
2010-05-26 | E-GEOD-8219 | biostudies-arrayexpress
Project description:Single Molecule Real Time (SMRT) sequencing was utilized to map the genome-wide DNA methylation pattern, and to identify consensus modified motifs in B. burgdorferi as well as isogenic methyltransferase mutants. Four conserved m6A modification motifs were identified, and were fully attributable to the presence of specific methyltransferases. Next, RNA-seq was compared between strains to determine the effects of altering global DNA methylation patterns on gene expression. Whole-genome transcriptome changes were observed in conjunction with the loss of methyltransferase enzymes, indicating that DNA methylation by restriction modification systems has effects on gene expression in B. burgdorferi.
2018-06-05 | GSE115308 | GEO
Project description:Borrelia burgdorferi, the causative agent of Lyme disease, is transmitted to vertebrate hosts by Ixodes ticks. As it moves from tick to host, B. burgdorferi must adapt to survive in a vastly different environment. During the tick bloodmeal, which lasts several days, B. burgdorferi is primed for mammalian infection, growing increasingly virulent as it senses cues from its surroundings in the tick. This conditioning is dependent on key transcriptional regulators; however, the downstream transcriptional changes occurring inside of the tick that promote B. burgdorferi transmission and infection are poorly understood due to technical difficulties in sequencing the B. burgdorferi transcriptome from inside of ticks. We developed a protocol to enrich and sequence B. burgdorferi from inside the tick, and we measured global transcriptional changes occurring in feeding ticks. We identified 192 genes that change expression twofold over the course of the tick bloodmeal, which were predominantly located on the plasmids of the genome. The majority of the upregulated genes encode proteins found at the cell envelope or proteins of unknown function, including 45 upregulated genes encoding outer surface lipoproteins. These genes that increase during feeding are candidates for future functional studies, which can help identify new targets for methods that aim to control the spread of Lyme disease.
2022-11-10 | GSE216261 | GEO
Project description:The Lyme disease spirochete Borrelia burgdorferi drives a range of acute and chronic maladies in humans and other incidental hosts infected with the pathogen. However, the primary vertebrate reservoir, Peromyscus leucopus appears spared from any symptomology following infection. This has led to a common hypothesis that P. leucopus and B. burgdorferi exist symbiotically: P. leucopus restrain their immune response against the microbe and enable the enzootic cycle while B. burgdorferi avoids causing damage to the host. While aspects of this hypothesis have been tested, the exact interactions that occur between P. leucopus and B. burgdorferi during infection remain largely unknown. Here we utilized an inbred colony of P. leucopus in order to compare B. burgdorferi (B31) fitness in these rodents to the traditional B. burgdorferi murine models—C57BL/6J and C3H/HeN Mus musculus, which develop signs of inflammation akin to human disease. We find that in contrast to our expectations, B. burgdorferi were able to reach much higher burdens in M. musculus, and that the overall kinetics of infection differed between the two rodent species. Surprisingly, we also found that P. leucopus remained infectious to larval Ixodes scapularis for a far shorter period than either M. musculus strain. In line with these observations, we found that P. leucopus does launch a modest but sustained inflammatory response against B. burgdorferi in the skin, which we hypothesize leads to reduced bacterial viability and infectivity in these hosts. These observations provide new insight into the nature of reservoir species and the B. burgdorferi enzootic cycle.
2024-01-03 | GSE244071 | GEO
Project description:Genomic analysis was performed to distinguish expression changes in murine medial edge epithelial cells during both palatal adherence and epithelial-mesenchymal transformation (EMT). Assessment of changes between sample 0 hours and sample 12 hours represent palatal adherence. Changes between sample 12 hours and sample 24 hours represent EMT. During adherence, we found that genes necessary for TGF-beta/LEF-1 signal transduction upregulate, as well as those necessary for cell adhesion. During EMT, we observed the loss of epithelial markers and upregulation of many genes necessary to promote the transition to mesenchyme and cell migration. Keywords = EMT Keywords = palate Keywords = LEF-1 Keywords = TGF-beta Keywords = craniofacial development Keywords: time-course
2005-07-18 | GSE2537 | GEO
Project description:Background: Lyme borrelia genotypes differ in their capacity to cause disseminated disease. Gene array analysis was employed to profile the host transcriptome induced by Borrelia burgdorferi strains with different capacities for causing disseminated disease in the blood of C3H/HeJ mice during early infection. Results: Borrelia burgdorferi B515, a clinical isolate that causes disseminated infection in mice, differentially regulated 236 transcripts (P<0.05 by ANOVA, with fold change of at least 2). The 216 significantly induced transcripts included IFN-responsive genes and genes involved in immunity and inflammation. In contrast, B. burgdorferi B331, a clinical isolate that causes transient skin infection but does not disseminate in C3H/HeJ mice, stimulated changes in only a few genes (1 induced, 4 repressed). Transcriptional regulation of type I IFN and IFN-related genes was measured by quantitative RT-PCR in mouse skin biopsies collected from the site of infection 24 hours after inoculation with B. burgdorferi. The mean values for transcript of Ifnb, Cxcl10, Gbp1, Ifit1, Ifit3, Irf7, Mx1, and Stat2, were found to be significantly increased in B. burgdorferi strain B515-infected mice relative to the control group. In contrast, transcription of these genes was not significantly changed in response to B. burgdorferi strain B331 or B31-4, a mutant that is unable to disseminate. Conclusions: These results establish a positive association between the disseminating capacity of B. burgdorferi and early type I IFN induction in a murine model of Lyme disease.
2016-03-25 | E-MTAB-3325 | biostudies-arrayexpress
Project description:Borelia burgdorferi, the causative agent of the Lyme disease, cycles between a vector (tick) and the mammalian host. Our principal goal is to study how B. burgdorferi adapts its metabolism to colonize and survive in the tick. We established the first growth-phase related acetylome and demonstrated the role of acetylation on central metabolism regulation. We also demonstrated that acetyl phosphate is the primary acetyl donor in B. burgdorferi.
2018-09-24 | PXD010065 | Pride
Project description:Borrelia burgdorferi, the causative agent of Lyme disease, is transmitted to vertebrate hosts by Ixodes ticks. As it moves from tick to host, B. burgdorferi must adapt to survive in a vastly different environment. During the tick bloodmeal, which lasts several days, B. burgdorferi is primed for mammalian infection, growing increasingly virulent as it senses cues from its surroundings in the tick. This conditioning is dependent on key transcriptional regulators; however, the downstream transcriptional changes occurring inside of the tick that promote B. burgdorferi transmission and infection are poorly understood due to technical difficulties in sequencing the B. burgdorferi transcriptome from inside of ticks. We developed a protocol to enrich and sequence B. burgdorferi from inside the tick, and we measured global transcriptional changes occurring in feeding ticks. We identified 192 genes that change expression twofold over the course of the tick bloodmeal, which were predominantly located on the plasmids of the genome. The majority of the upregulated genes encode proteins found at the cell envelope or proteins of unknown function, including 45 upregulated genes encoding outer surface lipoproteins. These genes that increase during feeding are candidates for future functional studies, which can help identify new targets for methods that aim to control the spread of Lyme disease.
2022-11-09 | GSE217146 | GEO
Project description:The gene NMB0419 of Neisseria meningitidis strain MC58 encodes a putative tetratricopeptide repeats (TPR) containing protein, which was implicated in respiratory epithelial invasion. We have accordingly sought a role for NMB0419 in meningococcal adherence and invasion of human epithelial cells using Escherichia coli surrogates. In trans expression of NMB0419 promoted adherence of the E. coli strain to human epithelial cells, which showed a unique aggregative adherence pattern that was observed for pathogenic E. coli. This adherence was totally abolished by addition of D-mannose, suggesting that formation of type 1 pili on the surface of E. coli strain was solely responsible for the adherence and was facilitated by the expression of NMB0419. This was further supported by rigid pilus structures seen on the surface of NMB0419 expressing E. coli using electron microscopy. A survey of other meningococcal strains including serogroup A, B, C, W, X, Y and Z (n=3, 42, 10, 1, 1, 1, and 1, respectively) revealed that an NMB0419 homologue was present in all strains, however, encoded varying number of TPR domains from 1 to 7. E. coli with in trans expression of such a homologue (NMA2065) encoding single TPR domain also showed enhanced adherence to the level that was observed for the E. coli strain expressing NMB0419 encoding for 4 TPR domains. Nevertheless, in-frame deletion of the TPR-domain coding sequence from the expression plasmid construct reduced the E. coli adherence to the background level. Revisit of the NMB0419 mutant strain of meningococcus indicated that reduction in adherence was primarily responsible for the reduced epithelial invasion that was previously observed. Study of transcriptome profiles in E. coli using microarray showed that the most significantly up-regulated genes in NMB0419 expressing E. coli belonging to the fim operon encoding all necessary structure proteins and chaperons for type 1 pili, strongly suggesting a gene regulatory role for NMB0419. Although the mechanism yet to be explored, this is the first study to showed that TPR domains are involved in bacterial adherence and that a gene encoding single functional TPR domain produced the same phenotype as a homologue encoding multiple TPR domains did.
2010-11-27 | E-MEXP-2485 | biostudies-arrayexpress