DksA plays an essential role in regulating the virulence of <i>Borrelia burgdorferi</i>

Mason, Charlotte; Thompson, C.; Ouyang, Zhiming

doi:10.1111/mmi.14504

Cited by 16 publications

(32 citation statements)

References 59 publications

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“…al. performed concurrently with our own investigation showed DksA is required for the infection of mice following intradermal inoculation with B. burgdorferi (63). Consistent with the data shown in our study, the requirement of DksA for mammalian infection was linked with dysregulation of the Rrp2-RpoN-RpoS pathway.…”

Section: Resultsmentioning

confidence: 75%

“…al. that showed DksA was required for the expression of RpoS-regulated genes and for infection of mice following intradermal inoculation, however, the seroconversion of mice infected with dksA-deficient B. burgdorferi were not reported in that study (63). Therefore, DksA appears to play a stronger role in controlling the expression of lipoproteins required for mammalian infection than (p)ppGpp.…”

Section: Activation Of the B Burgdorferi Stringent Response By Changmentioning

confidence: 70%

“…al. that showed DksA was required for the expression of RpoS-regulated genes and for infection of mice following intradermal inoculation, however, the seroconversion of mice infected with dksA -deficient B. burgdorferi were not reported in that study (63). While DksA is required for mammalian infection by B. burgdorferi following intradermal or intraperitoneal inoculation, it is not essential for colonization of I. scapularis .…”

Section: Discussionmentioning

confidence: 88%

“…Previous studies have demonstrated B. burgdorferi strains with mutations of dksA show a low levels of expression of genes under the control of the Rrp2-RpoN-RpoS regulatory cascade (e.g. dbpA, ospC, bba66) compared to wild-type controls (11,63). The expression of genes under the control of the Rrp2-RpoN-RpoS pathway are known to increase during growth in mildly acidic BSKII, pH 6.7 medium and with the addition of organic acids such as acetate (5,33,64).…”

Section: Dksa Contributes To Post-transcriptional Regulation Of Rposmentioning

confidence: 99%

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DksA-dependent regulation of RpoS contributes toBorrelia burgdorferitick-borne transmission and mammalian infectivity

Boyle

Richards²,

Dulebohn³

et al. 2020

Preprint

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Throughout its enzootic cycle, the Lyme disease spirochete Borreliella ( Borrelia ) burgdorferi , senses and responds to changes in its environment by using a small repertoire of transcription factors which coordinate the expression of genes required for infection of Ixodes ticks and various mammalian hosts. Among these transcription factors, the DnaK suppressor protein (DksA) plays a pivotal role in regulating gene expression in B. burgdorferi during periods of nutrient limitation and is required for mammalian infectivity. In many pathogenic bacteria, the gene regulatory activity of DksA along with the alarmone guanosine penta- and tetra-phosphate ((p)ppGpp) coordinates the stringent response to various environmental stresses including nutrient limitation. In this study, we sought to characterize the role of DksA in regulating the transcriptional activity of RNA polymerase and in the regulation of RpoS-dependent gene expression required for B. burgdorferi infectivity. Using in vitro transcription assays, we observed recombinant DksA inhibits RpoD-dependent transcription by B. burgdorferi RNA polymerase independent of ppGpp Additionally, we determined the pH-inducible expression of RpoS-dependent genes relies on DksA, but is independent of (p)ppGpp produced by Rel bbu . Subsequent transcriptomic and western blot assays indicated DksA regulates the expression of BBD18, a protein previously implicated in the post-transcriptional regulation of RpoS. Moreover, we observed DksA was required for infection of mice following intraperitoneal inoculation or for transmission of B. burgdorferi by Ixodes scapularis nymphs. Together, these data suggest DksA plays a central role in coordinating transcriptional responses of B. burgdorferi required for infectivity through its interactions with RNA polymerase and post-transcriptional control of RpoS.

show abstract

Section: Resultsmentioning

confidence: 75%

Section: Activation Of the B Burgdorferi Stringent Response By Changmentioning

confidence: 70%

“…al. that showed DksA was required for the expression of RpoS-regulated genes and for infection of mice following intradermal inoculation, however, the seroconversion of mice infected with dksA -deficient B. burgdorferi were not reported in that study (63). While DksA is required for mammalian infection by B. burgdorferi following intradermal or intraperitoneal inoculation, it is not essential for colonization of I. scapularis .…”

Section: Discussionmentioning

confidence: 88%

Section: Dksa Contributes To Post-transcriptional Regulation Of Rposmentioning

confidence: 99%

See 2 more Smart Citations

DksA-dependent regulation of RpoS contributes toBorrelia burgdorferitick-borne transmission and mammalian infectivity

Boyle

Richards²,

Dulebohn³

et al. 2020

Preprint

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show abstract

“…Rrp2, along with transcriptional activator BosR and repressor BadR, activates the RpoN-RpoS (σ 54 -σ S ) sigma cascade, which in turn controls the production of OspC and several virulence factors [ 14 – 28 ]. Several additional regulators have been identified that differentially regulate gene expression during the tick-mammal transmission including DsrA [ 29 ], Hfq [ 30 ], Hbb [ 31 , 32 ], CsrA [ 33 – 35 ], BpuR [ 36 ], EbfC [ 37 ], BpaB [ 38 ], SpoVG [ 39 ], BBD18 [ 40 ], LptA [ 41 ], BadP [ 42 ] and DksA [ 43 , 44 ].…”

Section: Introductionmentioning

confidence: 99%

YebC regulates variable surface antigen VlsE expression and is required for host immune evasion in Borrelia burgdorferi

et al. 2020

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Borrelia burgdorferi , the Lyme disease pathogen causes persistent infection by evading the host immune response. Differential expression of the surface-exposed lipoprotein VlsE that undergoes antigenic variation is a key immune evasion strategy employed by B . burgdorferi . Most studies focused on the mechanism of VlsE antigen variation, but little is known about VlsE regulation and factor(s) that regulates differential vlsE expression. In this study, we investigated BB0025, a putative YebC family transcriptional regulator (and hence designated BB0025 as YebC of B . burgdorferi herein). We constructed yebC mutant and complemented strain in an infectious strain of B . burgdorferi . The yebC mutant could infect immunocompromised SCID mice but not immunocompetent mice, suggesting that YebC plays an important role in evading host adaptive immunity. RNA-seq analyses identified vlsE as one of the genes whose expression was most affected by YebC. Quantitative RT-PCR and Western blot analyses confirmed that vlsE expression was dependent on YebC. In vitro , YebC and VlsE were co-regulated in response to growth temperature. In mice, both yebC and vlsE were inversely expressed with ospC in response to the host adaptive immune response. Furthermore, EMSA proved that YebC directly binds to the vlsE promoter, suggesting a direct transcriptional control. These data demonstrate that YebC is a new regulator that modulates expression of vlsE and other genes important for spirochetal infection and immune evasion in the mammalian host.

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Linear Chromosome in Borreliella: Island of Genetic Stability

Norek

2021

Developmental Biology in Prokaryotes and Lower Eukaryotes

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DksA plays an essential role in regulating the virulence of Borrelia burgdorferi

Abstract: Borrelia burgdorferi, the etiological agent for Lyme disease, survives in nature through a complex enzootic life cycle involving Ixodes ticks and many mammalian hosts (

Cited by 16 publications

References 59 publications

DksA-dependent regulation of RpoS contributes toBorrelia burgdorferitick-borne transmission and mammalian infectivity

DksA-dependent regulation of RpoS contributes toBorrelia burgdorferitick-borne transmission and mammalian infectivity

YebC regulates variable surface antigen VlsE expression and is required for host immune evasion in Borrelia burgdorferi

Linear Chromosome in Borreliella: Island of Genetic Stability

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