A Differential Role for BB0365 in the Persistence of<i>Borrelia burgdorferi</i>in Mice and Ticks

Pal, Utpal; Dai, Jianfeng; Li, Xin; Neelakanta, Girish; Luo, Phoebe; Kumar, Manish; Wang, Penghua; Yang, Xiuli; Anderson, John F.; Fikrig, Erol

doi:10.1086/523764

Cited by 46 publications

(66 citation statements)

References 33 publications

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“…Recent research investigating borrelia-vector interactions have focused on inactivation of global regulators, individual genes, and replicons to advance our understanding of B. burgdorferi tick colonization and persistence and vector transmission mechanisms (1,4,7,18,(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54). The loss of BBA66 activity did not completely abolish the ability of B. burgdorferi to invade the host by tick bite (at least when more than 4 ticks/mouse fed to repletion), but mouse infectivity was significantly impaired.…”

Section: Discussionmentioning

confidence: 99%

Borrelia burgdorferi bba66 Gene Inactivation Results in Attenuated Mouse Infection by Tick Transmission

et al. 2013

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bThe impact of the Borrelia burgdorferi surface-localized immunogenic lipoprotein BBA66 on vector and host infection was evaluated by inactivating the encoding gene, bba66, and characterizing the mutant phenotype throughout the natural mouse-tickmouse cycle. The BBA66-deficient mutant isolate, Bb ⌬A66 , remained infectious in mice by needle inoculation of cultured organisms, but differences in spirochete burden and pathology in the tibiotarsal joint were observed relative to the parental wild-type (WT) strain. Ixodes scapularis larvae successfully acquired Bb ⌬A66 following feeding on infected mice, and the organisms persisted in these ticks through the molt to nymphs. A series of tick transmission experiments (n ‫؍‬ 7) demonstrated that the ability of Bb ⌬A66 -infected nymphs to infect laboratory mice was significantly impaired compared to that of mice fed upon by WT-infected ticks. trans-complementation of Bb ⌬A66 with an intact copy of bba66 restored the WT infectious phenotype in mice via tick transmission. These results suggest a role for BBA66 in facilitating B. burgdorferi dissemination and transmission from the tick vector to the mammalian host as part of the disease process for Lyme borreliosis.

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Section: Discussionmentioning

confidence: 99%

Borrelia burgdorferi bba66 Gene Inactivation Results in Attenuated Mouse Infection by Tick Transmission

et al. 2013

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“…The decreased ability of PdeB-deficient spirochetes to survive within replete ticks may suggest that the degradation of c-di-GMP controls the expression and/or activity of B. burgdorferi gene products required to withstand growth within the flat midgut environment. Recently, constructed bb0323, bb0365, guaAB, dps, ospA/B, and bptA mutant strains exhibited defects in the ability to survive in ticks (41,53,64,68,73,98,99). Furthermore, the bba52, bba64, or bba07 mutant was reported to be unable to transmit spirochetes from ticks to naïve mice, although each of the mutants was able to infect mice by needle inoculation (32,48,97).…”

Section: Discussionmentioning

confidence: 99%

Analysis of the HD-GYP Domain Cyclic Dimeric GMP Phosphodiesterase Reveals a Role in Motility and the Enzootic Life Cycle of Borrelia burgdorferi

et al. 2011

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HD-GYP domain cyclic dimeric GMP (c-di-GMP) phosphodiesterases are implicated in motility and virulence in bacteria. Borrelia burgdorferi possesses a single set of c-di-GMP-metabolizing enzymes, including a putative HD-GYP domain protein, BB0374. Recently, we characterized the EAL domain phosphodiesterase PdeA. A mutation in pdeA resulted in cells that were defective in motility and virulence. Here we demonstrate that BB0374/PdeB specifically hydrolyzed c-di-GMP with a K m of 2.9 nM, confirming that it is a functional phosphodiesterase. Furthermore, by measuring phosphodiesterase enzyme activity in extracts from cells containing the pdeA pdeB double mutant, we demonstrate that no additional phosphodiesterases are present in B. burgdorferi. pdeB single mutant cells exhibit significantly increased flexing, indicating a role for c-di-GMP in motility. Constructing and analyzing a pilZ pdeB double mutant suggests that PilZ likely interacts with chemotaxis signaling. While virulence in needle-inoculated C3H/HeN mice did not appear to be altered significantly in pdeB mutant cells, these cells exhibited a reduced ability to survive in Ixodes scapularis ticks. Consequently, those ticks were unable to transmit the infection to naïve mice. All of these phenotypes were restored when the mutant was complemented. Identification of this role of pdeB increases our understanding of the c-di-GMP signaling network in motility regulation and the life cycle of B. burgdorferi.

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“…Many RpoS-activated genes appeared to be differentially expressed during tick feeding, and some, including ospC, dbpAB, BBK32, oppA5, BBA64, and BBA66, have been shown to be required for or associated with mammalian host infection (10,14,15,19,21,22,29,30,43,44). In addition, an increased level of RpoS leads to the repression of a group of genes that are associated with spirochetal colonization and survival in ticks, including ospA and BB0365 (6,8,34).…”

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confidence: 99%

Essential Role of the Response Regulator Rrp2 in the Infectious Cycle of Borrelia burgdorferi

et al. 2008

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Alteration of surface lipoprotein profiles is a key strategy that the Lyme disease pathogen, Borrelia burgdorferi, has evolved to be maintained within its enzootic cycle between arthropods and mammals. Accumulated evidence indicates that the central regulatory pathway controlling differential gene expression by B. burgdorferi is the RpoN-RpoS pathway (the 54 -S sigma factor cascade). It was previously shown that activation of the RpoN-RpoS pathway is controlled by Rrp2, a two-component response regulator and 54 -dependent transcriptional activator. The role of Rrp2 in the infectious cycle of B. burgdorferi has not been determined heretofore. In this report, we demonstrate that an rrp2 mutant defective in activating 54 -dependent transcription was unable to establish infection in mice, but the rrp2 mutant was capable of surviving within ticks during and after tick feeding. Because the rrp2 mutant was defective in the production of OspC, an outer surface lipoprotein essential for mammalian host infection, we further examined whether the loss of infectivity of the rrp2 mutant was solely due to the inability to produce OspC. While transformation with a shuttle vector carrying ospC under the control of a constitutive flaB promoter restored infection to an ospC mutant in immunodeficient SCID mice, it could not rescue the avirulent phenotype of the rrp2 mutant. These data indicate that, in addition to controlling OspC, Rrp2 controls another factor(s) essential for B. burgdorferi to establish infection in mammals. Furthermore, microarray analyses revealed that 125 and 19 genes were positively and negatively regulated, respectively, by Rrp2, which provides a foundation for future identification of additional Rrp2-dependent virulence determinants in B. burgdorferi.

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A Differential Role for BB0365 in the Persistence ofBorrelia burgdorferiin Mice and Ticks

Cited by 46 publications

References 33 publications

Borrelia burgdorferi bba66 Gene Inactivation Results in Attenuated Mouse Infection by Tick Transmission

Borrelia burgdorferi bba66 Gene Inactivation Results in Attenuated Mouse Infection by Tick Transmission

Analysis of the HD-GYP Domain Cyclic Dimeric GMP Phosphodiesterase Reveals a Role in Motility and the Enzootic Life Cycle of Borrelia burgdorferi

Essential Role of the Response Regulator Rrp2 in the Infectious Cycle of Borrelia burgdorferi

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