The Stringent Response-Regulated sRNA Transcriptome of Borrelia burgdorferi

Drecktrah, Dan; Hall, Laura S.; Rescheneder, Philipp; Lybecker, Meghan; Samuels, D. Scott

doi:10.3389/fcimb.2018.00231

Cited by 22 publications

(41 citation statements)

References 101 publications

(185 reference statements)

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“…In the pathogen Borrelia burgdorferi, a connection between the stringent response and the expression of 241 sRNAs was recently stablished, 187 of which were upregulated during nutrient stress (Drecktrah et al, 2018). The authors of the aforementioned study described potential mechanisms of regulation by Rel Bbu on transcription and fate of some transcripts, such as destabilization of the glycerol uptake facilitator transcript, glpF.…”

Section: The Stringent Response and Mrna Degradationmentioning

confidence: 99%

Regulation of mRNA Stability During Bacterial Stress Responses

Vargas-Blanco

Shell

2020

Front. Microbiol.

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Bacteria have a remarkable ability to sense environmental changes, swiftly regulating their transcriptional and posttranscriptional machinery as a response. Under conditions that cause growth to slow or stop, bacteria typically stabilize their transcriptomes in what has been shown to be a conserved stress response. In recent years, diverse studies have elucidated many of the mechanisms underlying mRNA degradation, yet an understanding of the regulation of mRNA degradation under stress conditions remains elusive. In this review we discuss the diverse mechanisms that have been shown to affect mRNA stability in bacteria. While many of these mechanisms are transcript-specific, they provide insight into possible mechanisms of global mRNA stabilization. To that end, we have compiled information on how mRNA fate is affected by RNA secondary structures; interaction with ribosomes, RNA binding proteins, and small RNAs; RNA base modifications; the chemical nature of 5 ends; activity and concentration of RNases and other degradation proteins; mRNA and RNase localization; and the stringent response. We also provide an analysis of reported relationships between mRNA abundance and mRNA stability, and discuss the importance of stress-associated mRNA stabilization as a potential target for therapeutic development.

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Section: The Stringent Response and Mrna Degradationmentioning

confidence: 99%

Regulation of mRNA Stability During Bacterial Stress Responses

Vargas-Blanco

Shell

2020

Front. Microbiol.

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“…However, Bb6S RNA levels increased in the tick as fed larvae molted into unfed nymphs and then decreased after nymphs fed to repletion (Figure ), which suggests a role in persistence in the tick (Caimano et al, ). Furthermore, we have recently shown that Rel Bbu and the stringent response upregulate Bb6S RNA (Drecktrah et al, ), implying that the mechanism of Bb6S RNA accumulation in the tick may involve (p)ppGpp and nutrient deprivation. However, we found that the absence of ssrS had little effect on persistence in the tick throughout the larval and nymph stages (Figure ).…”

Section: Discussionmentioning

confidence: 99%

“…An sRNA was recently shown to be expressed in the non‐coding sRNA transcriptomes of B. burgdorferi (Arnold et al, ; Drecktrah, Hall, Rescheneder, Lybecker, & Samuels, ; Popitsch, Bilusic, Rescheneder, Schroeder, & Lybecker, ) from the region of the genome predicted to encode Bb6S RNA (Barrick et al, ). In this study, we present experimental evidence to establish that this sRNA is indeed the canonical 6S RNA: we demonstrate specific binding of Bb6S RNA to RNAP in cells, describe the processing of Bb6S RNA by RNase Y, and examine the role of Bb6S RNA in murine infectivity and persistence in the tick.…”

Section: Discussionmentioning

confidence: 99%

“…Northern blots were probed with either single‐stranded RNA as previously described (Lybecker et al, ) or oligonucleotides as previously described (Drecktrah et al, ; Popitsch et al, ). Briefly, Bb6S, flaA , 5S RNA and tmRNA probes were constructed by PCR amplification of B. burgdorferi genomic DNA using primers 6S 19F and 6S 180R + T7, primers flaA 64F and flaA 284R + T7, primers rrf 7F and rrf 110 + T7, and primers ssrA 53F and ssrA 231R + T7, respectively, followed by in vitro transcription with the MEGAScript T7 kit (Ambion) using biotin‐16‐UTP (Roche) according to the manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

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Characterization of 6S RNA in the Lyme disease spirochete

Drecktrah

Hall

Brinkworth

et al. 2019

Molecular Microbiology

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6S RNA binds to RNA polymerase and regulates gene expression, contributing to bacterial adaptation to environmental stresses. In this study, we examined the role of 6S RNA in murine infectivity and tick persistence of the Lyme disease spirochete Borrelia (Borreliella) burgdorferi. B. burgdorferi 6S RNA (Bb6S RNA) binds to RNA polymerase, is expressed independent of growth phase or nutrient stress in culture, and is processed by RNase Y. We found that rny (bb0504), the gene encoding RNase Y, is essential for B. burgdorferi growth, while ssrS, the gene encoding 6S RNA, is not essential, indicating a broader role for RNase Y activity in the spirochete. Bb6S RNA regulates expression of the ospC and dbpA genes encoding outer surface protein C and decorin binding protein A, respectively, which are lipoproteins important for host infection. The highest levels of Bb6S RNA are found when the spirochete resides in unfed nymphs. ssrS mutants lacking Bb6S RNA were compromised for infectivity by needle inoculation, but injected mice seroconverted, indicating an ability to activate the adaptive immune response. ssrS mutants were successfully acquired by larval ticks and persisted through fed nymphs. Bb6S RNA is one of the first regulatory RNAs identified in B. burgdorferi that controls the expression of lipoproteins involved in host infectivity.

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“…burgdorferi noncoding transcriptome [ 30 ]. A later study by other researchers used different criteria for calling putative ncRNAs, resulting in a somewhat different list [ 49 , 50 ]. Although the later list was not used in the current analyses, our raw data are readily accessible to anyone who wishes to analyze them against those or other transcript sets (see Data Availability, below).…”

Section: Methodsmentioning

confidence: 99%

Transcriptomic insights on the virulence-controlling CsrA, BadR, RpoN, and RpoS regulatory networks in the Lyme disease spirochete

et al. 2018

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Borrelia burgdorferi, the causative agent of Lyme disease, survives in nature through a cycle that alternates between ticks and vertebrates. To facilitate this defined lifestyle, B. burgdorferi has evolved a gene regulatory network that ensures transmission between those hosts, along with specific adaptations to niches within each host. Several regulatory proteins are known to be essential for the bacterium to complete these critical tasks, but interactions between regulators had not previously been investigated in detail, due to experimental uses of different strain backgrounds and growth conditions. To address that deficit in knowledge, the transcriptomic impacts of four critical regulatory proteins were examined in a uniform strain background. Pairs of mutants and their wild-type parent were grown simultaneously under a single, specific culture condition, permitting direct comparisons between the mutant strains. Transcriptomic analyses were strand-specific, and assayed both coding and noncoding RNAs. Intersection analyses identified regulatory overlaps between regulons, including transcripts involved in carbohydrate and polyamine metabolism. In addition, it was found that transcriptional units such as ospC and dbpBA, which were previously observed to be affected by alternative sigma factors, are transcribed by RNA polymerase using the housekeeping sigma factor, RpoD.

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The Stringent Response-Regulated sRNA Transcriptome of Borrelia burgdorferi

Cited by 22 publications

References 101 publications

Regulation of mRNA Stability During Bacterial Stress Responses

Regulation of mRNA Stability During Bacterial Stress Responses

Characterization of 6S RNA in the Lyme disease spirochete

Transcriptomic insights on the virulence-controlling CsrA, BadR, RpoN, and RpoS regulatory networks in the Lyme disease spirochete

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