Insights into the Biology of Borrelia burgdorferi Gained Through the Application of Molecular Genetics

Groshong, Ashley M.; Blevins, Jon S.

doi:10.1016/b978-0-12-800262-9.00002-0

Cited by 39 publications

(42 citation statements)

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“…Moreover, transcription of rpoS is regulated by RpoN, effectively decreasing the regulatory breadth of sigma factors in B. burgdorferi [11]. Transcription is also regulated via several characterized transcription factors in B. burgdorferi [5, 12–14] . However, little is known about post-transcriptional gene regulation in this spirochete.…”

Section: Introductionmentioning

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: Introductionmentioning

confidence: 99%

Temperature-dependent sRNA transcriptome of the Lyme disease spirochete

et al. 2017

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“…Differential gene expression is essential for the Lyme disease spirochete to endure the diverse and fluctuating environments encountered over the course of the enzootic cycle. Similar to other bacterial species (Stock et al, 2000; West and Stock, 2001; Kazmierczak et al, 2005; Beier and Gross, 2006; Tamayo et al, 2007), B. burgdorferi utilizes two-component systems (TCS) to modulate its gene expression (Fraser et al, 1997; Casjens et al, 2000; Radolf et al, 2012; Groshong and Blevins, 2014). Unlike many other species of bacteria, B. burgdorferi was reported to encode only two TCS—Hk1-Rrp1 and Hk2-Rrp2—that have demonstrated global gene regulatory capabilities (Yang et al, 2003a; Rogers et al, 2009; Samuels, 2011; Radolf et al, 2012; Groshong and Blevins, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…Similar to other bacterial species (Stock et al, 2000; West and Stock, 2001; Kazmierczak et al, 2005; Beier and Gross, 2006; Tamayo et al, 2007), B. burgdorferi utilizes two-component systems (TCS) to modulate its gene expression (Fraser et al, 1997; Casjens et al, 2000; Radolf et al, 2012; Groshong and Blevins, 2014). Unlike many other species of bacteria, B. burgdorferi was reported to encode only two TCS—Hk1-Rrp1 and Hk2-Rrp2—that have demonstrated global gene regulatory capabilities (Yang et al, 2003a; Rogers et al, 2009; Samuels, 2011; Radolf et al, 2012; Groshong and Blevins, 2014). The Hk2-Rrp2 TCS activates the expression of the stationary phase sigma factor RpoS synergistically with RpoN (Burtnick et al, 2007; Ouyang et al, 2008; Blevins et al, 2009), which, in turn, chiefly regulates plasmid-borne genes (Yang et al, 2003a,b; Caimano et al, 2007) and induces the expression of genes, such as ospC (Hübner et al, 2001), which are known to be important for mammalian infection (Caimano et al, 2004; Fisher et al, 2005; Caimano et al, 2007; Boardman et al, 2008; Ouyang et al, 2008; Dunham-Ems et al, 2012; Ouyang et al, 2012) as well as genes involved in chitobiose utilization, which has been shown to be important for colonization of the tick (Sze et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, the diguanylate cyclase, Rrp1, is active only when it is phosphorylated, presumably by the histidine sensor kinase, Hk1 (Caimano et al, 2011) (Figure 1). While Hk2-Rrp2 is primarily involved in mammalian host adaptation (Groshong and Blevins, 2014), recent studies suggest that c-di-GMP is a key regulator in the adaptive responses of B. burgdorferi to the tick environment (Caimano et al, 2011; He et al, 2011, 2014; Kostick et al, 2011; Pitzer et al, 2011; Sultan et al, 2011). While the genomes of several species of bacteria were reported to encode multiple c-di-GMP-metabolizing enzymes (Galperin et al, 1999, 2001; Galperin, 2004), both bioinformatics and experimental analysis indicate that B. burgdorferi possesses only a limited number of genes responsible for regulating c-di-GMP levels—one diguanylate cyclase ( bb0419 / rrp1 ), two distinct phosphodiesterases ( bb0363 / pdeA and bb0374 / pdeB ), and one c-di-GMP-binding PilZ-domain protein, PlzA ( bb0733 ) (Figure 1) (Ryjenkov et al, 2005; Rogers et al, 2009; Freedman et al, 2010; Sultan et al, 2010, 2011; Caimano et al, 2011; He et al, 2011; Kostick et al, 2011; Pitzer et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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The cyclic-di-GMP signaling pathway in the Lyme disease spirochete, Borrelia burgdorferi

Novak

Sultan

Motaleb

2014

Front. Cell. Infect. Microbiol.

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In nature, the Lyme disease spirochete Borrelia burgdorferi cycles between the unrelated environments of the Ixodes tick vector and mammalian host. In order to survive transmission between hosts, B. burgdorferi must be able to not only detect changes in its environment, but also rapidly and appropriately respond to these changes. One manner in which this obligate parasite regulates and adapts to its changing environment is through cyclic-di-GMP (c-di-GMP) signaling. c-di-GMP has been shown to be instrumental in orchestrating the adaptation of B. burgdorferi to the tick environment. B. burgdorferi possesses only one set of c-di-GMP-metabolizing genes (one diguanylate cyclase and two distinct phosphodiesterases) and one c-di-GMP-binding PilZ-domain protein designated as PlzA. While studies in the realm of c-di-GMP signaling in B. burgdorferi have exploded in the last few years, there are still many more questions than answers. Elucidation of the importance of c-di-GMP signaling to B. burgdorferi may lead to the identification of mechanisms that are critical for the survival of B. burgdorferi in the tick phase of the enzootic cycle as well as potentially delineate a role (if any) c-di-GMP may play in the transmission and virulence of B. burgdorferi during the enzootic cycle, thereby enabling the development of effective drugs for the prevention and/or treatment of Lyme disease.

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“…orrelia burgdorferi, the Lyme disease spirochete, shuttles principally between the Ixodes ticks and a vertebrate host during its natural infection cycle (1)(2)(3)(4)(5). In the tick, spirochetes reside primarily in the midgut until the introduction of the host blood meal.…”

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confidence: 99%

Motor Rotation Is Essential for the Formation of the Periplasmic Flagellar Ribbon, Cellular Morphology, and Borrelia burgdorferi Persistence within Ixodes scapularis Tick and Murine Hosts

Sultan

Sekar

Zhao³

et al. 2015

Infect Immun

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c Borrelia burgdorferi must migrate within and between its arthropod and mammalian hosts in order to complete its natural enzootic cycle. During tick feeding, the spirochete transmits from the tick to the host dermis, eventually colonizing and persisting within multiple, distant tissues. This dissemination modality suggests that flagellar motor rotation and, by extension, motility are crucial for infection. We recently reported that a nonmotile flaB mutant that lacks periplasmic flagella is rod shaped and unable to infect mice by needle or tick bite. However, those studies could not differentiate whether motor rotation or merely the possession of the periplasmic flagella was crucial for cellular morphology and host persistence. Here, we constructed and characterized a motB mutant that is nonmotile but retains its periplasmic flagella. Even though ⌬motB bacteria assembled flagella, part of the mutant cell is rod shaped. Cryoelectron tomography revealed that the flagellar ribbons are distorted in the mutant cells, indicating that motor rotation is essential for spirochetal flat-wave morphology. The ⌬motB cells are unable to infect mice, survive in the vector, or migrate out of the tick. Coinfection studies determined that the presence of these nonmotile ⌬motB cells has no effect on the clearance of wild-type spirochetes during murine infection and vice versa. Together, our data demonstrate that while flagellar motor rotation is necessary for spirochetal morphology and motility, the periplasmic flagella display no additional properties related to immune clearance and persistence within relevant hosts. Borrelia burgdorferi, the Lyme disease spirochete, shuttles principally between the Ixodes ticks and a vertebrate host during its natural infection cycle (1-5). In the tick, spirochetes reside primarily in the midgut until the introduction of the host blood meal. During tick feeding on a vertebrate host, spirochetes replicate, and a subset of the motile organisms cross the midgut epithelium into the hemocoel before reaching the salivary glands, where they subsequently are deposited into the host dermis (6-8). Once in the host, B. burgdorferi must migrate through the complex skin tissues, including some hematogenous dissemination, and eventually colonize distant tissues, where they often produce disease symptoms in certain hosts. Subsequently, when a naive tick feeds on an infected reservoir host, spirochetes in the skin migrate into the arthropod to complete the enzootic cycle (3, 4, 9). During the spirochete's migration within and between the hosts, periplasmic flagellar motor rotation and, by extension, motility are thought to be crucial for infection (10, 11). Indeed, nonmotile, reduced-motility, or nonchemotactic mutant spirochetes were found to be attenuated in mouse infection (12)(13)(14). Additionally, our data indicate that B. burgdorferi remains constantly motile in the mouse dermis, even 2 years after needle inoculation (P. Sekar, R. M. Wooten, and M. A. Motaleb, unpublished results). In fact, this Lyme dise...

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Insights into the Biology of Borrelia burgdorferi Gained Through the Application of Molecular Genetics

Cited by 39 publications

References 549 publications

Temperature-dependent sRNA transcriptome of the Lyme disease spirochete

Temperature-dependent sRNA transcriptome of the Lyme disease spirochete

The cyclic-di-GMP signaling pathway in the Lyme disease spirochete, Borrelia burgdorferi

Motor Rotation Is Essential for the Formation of the Periplasmic Flagellar Ribbon, Cellular Morphology, and Borrelia burgdorferi Persistence within Ixodes scapularis Tick and Murine Hosts

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