Borrelia burgdorferi, the Lyme disease spirochete, possesses genetically-encoded responses to doxycycline, but not to amoxicillin.
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ABSTRACT:
PROVIDER: PRJNA809913 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18121421_1.fastq.gz | Fastqsanger.gz | |||
| SRR18121421_2.fastq.gz | Fastqsanger.gz | |||
| SRR18121422_1.fastq.gz | Fastqsanger.gz | |||
| SRR18121422_2.fastq.gz | Fastqsanger.gz | |||
| SRR18121423_1.fastq.gz | Fastqsanger.gz |
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Project description:Purpose: To determine whether Borrelia burgdorferi, the spirochetal agent of Lyme disease, responds to sub-lethal doses of antibiotics. Methods: mRNA profiles of Borrelia burgdorferi were compared after subculturing in 0.2μg/mL amoxicillin, 0.2μg/mL doxycycline, or media control for 3h or 24h (n=3 per group) by paired-end sequencing using the Illumina NextSeq 500. The sequence reads were aligned using Salmon aligner followed by DESeq2 for differential expression analysis. Results: After culturing for 24 h in a sub-lethal concentration of doxycycline, there were significant increases in a substantial number of transcripts for proteins that are involved with translation. Bacteria continued to elongate, but appeared to be defective in septation and formed filaments. In contrast, incubation with sublethal concentration of amoxicillin led to membrane blebbing and swelling, indicative of cell wall disruption, but no significant changes in levels of any bacterial transcript. Conclusion: We conclude that B. burgdorferi has a mechanism(s) that detects translational inhibition by doxycycline, and increases production of translational machinery in compensation. In contrast, The absence of response to the inhibition of cell wall synthesis by amoxicillin implies that B. burgdorferi lacks a mechanism to assess cell wall integrity.
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Project description:The alternative sigma factor RpoS plays a central role in the critical host-adaptive response of the Lyme disease spirochete, Borrelia burgdorferi. We previously identified bbd18 as a negative regulator of RpoS but could not inactivate bbd18 in wild-type spirochetes. In the current study we employed an inducible bbd18 gene to demonstrate the essential nature of BBD18 for viability of wild-type spirochete viability in vitro and at a unique point in vivo. Transcriptomic analyses of BBD18 depleted cells demonstrated global induction of RpoS-dependent genes prior to lysis, with the absolute requirement for BBD18, both in vitro and in vivo, circumvented by deletion of rpoS. The increased expression of plasmid prophage genes and the presence of phage particles in the supernatants of lysing cultures indicate that RpoS regulates phage lysis-lysogeny decisions. Through this work we identify a mechanistic link between endogenous transducing prophages and the RpoS-dependent adaptive response of the Lyme disease spirochete. The alternative sigma factor RpoS plays a central role in the critical host-adaptive response of the Lyme disease spirochete, Borrelia burgdorferi. We previously identified bbd18 as a negative regulator of RpoS but could not inactivate bbd18 in wild-type spirochetes. In the current study we employed an inducible bbd18 gene to demonstrate the essential nature of BBD18 for viability of wild-type spirochete viability in vitro and at a unique point in vivo. Transcriptomic analyses of BBD18 depleted cells demonstrated global induction of RpoS-dependent genes prior to lysis, with the absolute requirement for BBD18, both in vitro and in vivo, circumvented by deletion of rpoS. The increased expression of plasmid prophage genes and the presence of phage particles in the supernatants of lysing cultures indicate that RpoS regulates phage lysis-lysogeny decisions. Through this work we identify a mechanistic link between endogenous transducing prophages and the RpoS-dependent adaptive response of the Lyme disease spirochete.
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Project description:Lyme disease is a result from an infection by the spirochete Borrelia burgdorferi, and is the leading vector-borne disease in North America. Due to the genomic and proteomic variability of different B. burgdorferi isolates, the study and further comparison of their proteome is key to understand the biology and infectivity of these spirochetes. Mass spectrometry-based proteomics was used to assemble peptide datasets of laboratory isolates B31, MM1, B31-ML23, and the infective isolates B31-5A4, B31-A3, and 297, as well as other public datasets, and is publicly available as the Borrelia PeptideAtlas (http://www.peptideatlas.org/builds/borrelia/). These datasets include information on total proteome, secretome, and membrane proteome of the B. burgdorferi.
2024-09-03 | PXD046281 | Pride
Project description:The pathogenic spirochete Borrelia burgdorferi senses and responds to diverse environmental challenges, including changes in nutrient availability, throughout its natural infectious cycle in Ixodes spp. ticks and mammalian hosts. This study examined the role of the putative DnaK suppressor protein (DksA) in the transcriptional response of B. burgdorferi to starvation. Wild-type and dksA-deficient B. burgdorferi strains were subjected to starvation by shifting mid-logarithmic cultures grown in BSK-II medium to serum-free RPMI medium for six hours under microaerobic conditions (5% CO2, 3% O2). Microarray analyses of wild-type B. burgdorferi revealed that genes encoding flagellar components, ribosomal proteins, and DNA replication machinery were downregulated in response to starvation. DksA mediated transcriptomic responses to starvation in B. burgdorferi as the dksA-deficient B. burgdorferi strain differentially expressed only 47 genes in response to starvation compared to the 500 genes differentially expressed by wild-type strains. Consistent with a role for DksA in the starvation response of B. burgdorferi, fewer CFUs were observed for dksA-deficient spirochetes after prolonged starvation in RPMI medium compared to wild-type B. burgdorferi. Transcriptomic analyses revealed a partial overlap between the DksA regulon and the regulon of the guanosine tetraphosphate and guanosine pentaphosphate [(p)ppGpp] synthase RelBbu, while the DksA regulon also included many plasmid-borne genes. Corresponding to a DksA-(p)ppGpp regulatory relationship, (p)ppGpp levels were constitutively elevated in the dksA-deficient strain compared to the wild-type strain. Together, these data indicate that DksA directs the stringent response with a regulatory interplay with (p)ppGpp that is fundamental to B. burgdorferi responses to the environment.
2018-12-18 | GSE119023 | GEO
Project description:DksA controls the response of the Lyme disease spirochete Borrelia burgdorferi to starvation
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Project description:Borrelia burgdorferi, the tick-transmitted spirochete agent of Lyme disease, has a highly segmented genome with a linear chromosome and various linear or circular plasmids. Here, by imaging several chromosomal loci and 16 distinct plasmids, we show that B. burgdorferi is polyploid during growth in culture and that the number of genome copies decreases during stationary phase. B. burgdorferi is also polyploid inside fed ticks and chromosome copies are regularly spaced along the spirochete’s length in both growing cultures and ticks. This patterning involves the conserved DNA partitioning protein ParA whose localization is controlled by a potentially phage-derived protein, ParZ, instead of its usual partner ParB. ParZ binds its owe coding region and acts as a centromere-binding protein. While ParA works with ParZ, ParB controls the localization of the condensin, SMC. Together, the ParA/ParZ and ParB/SMC pairs ensure faithful chromosome inheritance. Our findings underscore the plasticity of cellular functions, even those as fundamental as chromosome segregation.
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Project description:Adiponectin-mediated pathways contribute to mammalian homeostasis; however, little is known about adiponectin and adiponectin receptor signaling in arthropods. In this study, we demonstrate that Ixodes scapularis ticks have an adiponectin receptor-like protein (ISARL) but lack adiponectin, suggesting activation by alternative pathways. ISARL expression is significantly upregulated in the tick gut after Borrelia burgdorferi infection, suggesting that ISARL signaling may be co-opted by the Lyme disease agent. Consistent with this, RNA interference (RNAi)-mediated silencing of ISARL significantly reduced the B. burgdorferi burden in the tick. RNA-seq-based transcriptomics and RNAi assays demonstrate that ISARL-mediated phospholipid metabolism by phosphatidylserine synthase I is associated with B. burgdorferi survival. Furthermore, the tick complement C1q-like protein 3 interacts with ISARL, and B. burgdorferi facilitates this process. This study identifies a new tick metabolic pathway that is connected to the life cycle of the Lyme disease spirochete.
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Project description:Lyme disease spirochetes must induce RpoS-dependent genes during tick feeding to prepare for host infection. Previous work in our lab identified bbd18 as a negative regulator of RpoS, but inactivation of bbd18 in wild-type spirochetes was never achieved. In the current study we generated an inducible bbd18 gene at the endogenous plasmid locus and demonstrated the essential nature of BBD18 for viability of wild-type spirochetes in vitro and at a unique point in vivo. Transcriptomic analyses demonstrated global induction of RpoS and RpoS-dependent genes following BBD18 depletion, culminating in spirochete lysis. Plasmid prophage genes were also induced and phage particles were detected in lysed culture supernatants, suggesting that RpoS regulates phage lysis-lysogeny decisions. The absolute requirement for BBD18 persisted following displacement of the entire set of cp32 plasmid prophages but could be circumvented by deletion of rpoS. This is the first report of a mechanistic link between endogenous transducing prophages and the RpoS-dependent adaptive response of the Lyme disease spirochete.
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2023-05-26 | GSE222085 | GEO