Interaction of the Lyme disease spirochete with its tick vector

Caimano, Melissa J.; Drecktrah, Dan; Kung, Faith; Samuels, D. Scott

doi:10.1111/cmi.12609

Cited by 86 publications

(124 citation statements)

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“…2a). Notably, asRNAs were identified opposite to key genes active in the maintenance of the B. burgdorferi life cycle and cell division, such as: bb0420 ( hk1 ), bb0827 ( hrpA ), bbb03 ( resT ), bbb17 ( guaB ), and bba66 [4, 13, 44–50]. Hk1 is the histidine kinase in the two-component system necessary for B. burgdorferi survival in the tick [45].…”

Section: Resultsmentioning

confidence: 99%

Temperature-dependent sRNA transcriptome of the Lyme disease spirochete

et al. 2017

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BackgroundTransmission of Borrelia burgdorferi from its tick vector to a vertebrate host requires extensive reprogramming of gene expression. Small regulatory RNAs (sRNA) have emerged in the last decade as important regulators of bacterial gene expression. Despite the widespread observation of sRNA-mediated gene regulation, only one sRNA has been characterized in the Lyme disease spirochete B. burgdorferi. We employed an sRNA-specific deep-sequencing approach to identify the small RNA transcriptome of B. burgdorferi at both 23 °C and 37 °C, which mimics in vitro the transmission from the tick vector to the mammalian host.ResultsWe identified over 1000 sRNAs in B. burgdorferi revealing large amounts of antisense and intragenic sRNAs, as well as characteristic intergenic and 5′ UTR-associated sRNAs. A large fraction of the novel sRNAs (43%) are temperature-dependent and differentially expressed at the two temperatures, suggesting a role in gene regulation for adaptation during transmission. In addition, many genes important for maintenance of Borrelia during its enzootic cycle are associated with antisense RNAs or 5′ UTR sRNAs. RNA-seq data were validated for twenty-two of the sRNAs via Northern blot analyses.ConclusionsOur study demonstrates that sRNAs are abundant and differentially expressed by environmental conditions suggesting that gene regulation via sRNAs is a common mechanism utilized in B. burgdorferi. In addition, the identification of antisense and intragenic sRNAs impacts the broadly used loss-of-function genetic approach used to study gene function and increases the coding potential of a small genome. To facilitate access to the analyzed RNA-seq data we have set-up a website at http://www.cibiv.at/~niko/bbdb/ that includes a UCSC browser track hub. By clicking on the respective link, researchers can interactively inspect the data in the UCSC genome browser (Kent et al., Genome Res 12:996-1006, 2002).Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3398-3) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Temperature-dependent sRNA transcriptome of the Lyme disease spirochete

et al. 2017

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“…Nymphs molt to adults that feed, mate, and lay eggs to continue the cycle (adapted from Caimano et al). 7 …”

Section: Figmentioning

confidence: 99%

“…1). 5–7 Ixodes larvae acquire B. burgdorferi by feeding on a mammalian host, and the spirochetes inhabit the midgut. The larvae molt and, when the resulting nymphs feed, the spirochetes leave the midgut, enter the hemocoel, migrate to the salivary glands, and transmit to the vertebrate source of the blood meal.…”

Section: Introductionmentioning

confidence: 99%

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Gene Regulation During the Enzootic Cycle of the Lyme Disease Spirochete

Samuels

2016

Forum Immun Dis Ther

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Borrelia burgdorferi, the spirochete that causes Lyme disease, exists in an enzootic cycle, alternating between a tick vector and a vertebrate host. To adapt to and survive the environmental changes associated with its enzootic cycle, including nutrient availability, B. burgdorferi uses three different systems to regulate the expression of genes: RpoN-RpoS, histidine kinase (Hk)1/response regulator 1 (Rrp1), and RelBbu. The RpoN-RpoS alternative sigma factor cascade activates genes required for transmission from the tick to the vertebrate, maintenance of the vertebrate infection, and persistence in the tick. RelBbu controls the levels of the alarmones guanosine pentaphosphate and guanosine tetraphosphate, which are necessary for surviving the nutrient-deficient conditions in the midgut of the tick following absorption of the blood meal and the subsequent molt. The Hk1/Rrp1 two-component system produces cyclic dimeric guanosine monophosphate that regulates the genes required for the transitions between the tick and vertebrate as well as protective responses to the blood meal.

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“…As a tick-borne pathogen, Bb cycles between the Ixodes tick vector and mammals in its natural environment 10,16 . It is possible that Bb requires thiamin for its survival in vivo , but it lacks a role for it in vitro .…”

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Lyme disease spirochaete Borrelia burgdorferi does not require thiamin

et al. 2016

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Thiamin pyrophosphate (ThDP), the active form of thiamin (vitamin B1), is believed to be an essential cofactor for all living organisms1,2. Here, we report the unprecedented result that thiamin is dispensable for the growth of the Lyme disease pathogen Borrelia burgdorferi (Bb)3. Bb lacks genes for thiamin biosynthesis and transport as well as known ThDP-dependent enzymes4, and we were unable to detect thiamin or its derivatives in Bb cells. We showed that eliminating thiamin in vitro and in vivo using BcmE, an enzyme that degrades thiamin, has no impact on Bb growth and survival during its enzootic infectious cycle. Finally, high-performance liquid chromatography analysis reveals that the level of thiamin and its derivatives in Ixodes scapularis ticks, the enzootic vector of Bb, is extremely low. These results suggest that by dispensing with use of thiamin, Borrelia, and perhaps other tick-transmitted bacterial pathogens, are uniquely adapted to survive in tick vectors before transmitting to mammalian hosts. To our knowledge, such a mechanism has not been reported previously in any living organisms.

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Interaction of the Lyme disease spirochete with its tick vector

Cited by 86 publications

References 77 publications

Temperature-dependent sRNA transcriptome of the Lyme disease spirochete

Temperature-dependent sRNA transcriptome of the Lyme disease spirochete

Gene Regulation During the Enzootic Cycle of the Lyme Disease Spirochete

Lyme disease spirochaete Borrelia burgdorferi does not require thiamin

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