Life Cycle of Borrelia burgdorferi sensu lato and Transmission to Humans

2009 ◽  
pp. 18-30 ◽  
Author(s):  
Lise Gern
Keyword(s):  
Life Cycle ◽  
Borrelia Burgdorferi

scholarly journals Borrelia burgdorferi Lacking BBK32, a Fibronectin-Binding Protein, Retains Full Pathogenicity

2006 ◽  
Vol 74 (6) ◽  
pp. 3305-3313 ◽  
Author(s):  
Xin Li ◽  
Xianzhong Liu ◽  
Deborah S. Beck ◽  
Fred S. Kantor ◽  
Erol Fikrig
Keyword(s):  
Life Cycle ◽  
Borrelia Burgdorferi ◽  
Deletion Mutant ◽  
Binding Protein ◽  
Kanamycin Resistance ◽  
Binding Activity ◽  
Mammalian Host ◽  
Wild Type ◽  
Fibronectin Binding Protein ◽  
Fibronectin Binding

ABSTRACT BBK32, a fibronectin-binding protein of Borrelia burgdorferi, is one of many surface lipoproteins that are differentially expressed by the Lyme disease spirochete at various stages of its life cycle. The level of BBK32 expression in B. burgdorferi is highest during infection of the mammalian host and lowest in flat ticks. This temporal expression profile, along with its fibronectin-binding activity, strongly suggests that BBK32 may play an important role in Lyme pathogenesis in the host. To test this hypothesis, we constructed an isogenic BBK32 deletion mutant from wild-type B. burgdorferi B31 by replacing the BBK32 gene with a kanamycin resistance cassette through homologous recombination. We examined both the wild-type strain and the BBK32 deletion mutant extensively in the experimental mouse-tick model of the Borrelia life cycle. Our data indicated that B. burgdorferi lacking BBK32 retained full pathogenicity in mice, regardless of whether mice were infected artificially by syringe inoculation or naturally by tick bite. The loss of BBK32 expression in the mutant had no adverse effect on spirochete acquisition (mouse-to-tick) and transmission (tick-to-mouse) processes. These results suggest that additional B. burgdorferi proteins can complement the function of BBK32, fibronectin binding or otherwise, during the natural spirochete life cycle.

scholarly journals An Ixodes scapularis Protein Disulfide Isomerase Contributes to Borrelia burgdorferi Colonization of the Vector

2020 ◽  
Vol 88 (12) ◽  
Author(s):  
Yongguo Cao ◽  
Connor Rosen ◽  
Gunjan Arora ◽  
Akash Gupta ◽  
Carmen J. Booth ◽  
...  
Keyword(s):  
Life Cycle ◽  
Borrelia Burgdorferi ◽  
Protein Disulfide Isomerase ◽  
Inflammatory Responses ◽  
Ixodes Scapularis ◽  
Vertebrate Host ◽  
Content Type ◽  
Disulfide Isomerase ◽  
Complex Interactions ◽  
Protein Disulfide

ABSTRACT Borrelia burgdorferi causes Lyme disease, the most common tick-transmitted illness in North America. When Ixodes scapularis feed on an infected vertebrate host, spirochetes enter the tick gut along with the bloodmeal and colonize the vector. Here, we show that a secreted tick protein, I. scapularis protein disulfide isomerase A3 (IsPDIA3), enhances B. burgdorferi colonization of the tick gut. I. scapularis ticks in which ispdiA3 has been knocked down using RNA interference have decreased spirochete colonization of the tick gut after engorging on B. burgdorferi-infected mice. Moreover, administration of IsPDIA3 antiserum to B. burgdorferi-infected mice reduced the ability of spirochetes to colonize the tick when feeding on these animals. We show that IsPDIA3 modulates inflammatory responses at the tick bite site, potentially facilitating spirochete survival at the vector-host interface as it exits the vertebrate host to enter the tick gut. These data provide functional insights into the complex interactions between B. burgdorferi and its arthropod vector and suggest additional targets to interfere with the spirochete life cycle.

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

2011 ◽  
Vol 79 (8) ◽  
pp. 3273-3283 ◽  
Author(s):  
Syed Z. Sultan ◽  
Joshua E. Pitzer ◽  
Tristan Boquoi ◽  
Gerry Hobbs ◽  
Michael R. Miller ◽  
...  
Keyword(s):  
Life Cycle ◽  
Borrelia Burgdorferi ◽  
Double Mutant ◽  
Ixodes Scapularis ◽  
Metabolizing Enzymes ◽  
Content Type ◽  
Motility Regulation ◽  
Mutant Cells ◽  
Single Set

ABSTRACTHD-GYP domain cyclic dimeric GMP (c-di-GMP) phosphodiesterases are implicated in motility and virulence in bacteria.Borrelia burgdorferipossesses 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 inpdeAresulted in cells that were defective in motility and virulence. Here we demonstrate that BB0374/PdeB specifically hydrolyzed c-di-GMP with aKmof 2.9 nM, confirming that it is a functional phosphodiesterase. Furthermore, by measuring phosphodiesterase enzyme activity in extracts from cells containing thepdeA pdeBdouble mutant, we demonstrate that no additional phosphodiesterases are present inB. burgdorferi.pdeBsingle mutant cells exhibit significantly increased flexing, indicating a role for c-di-GMP in motility. Constructing and analyzing apilZpdeBdouble mutant suggests that PilZ likely interacts with chemotaxis signaling. While virulence in needle-inoculated C3H/HeN mice did not appear to be altered significantly inpdeBmutant cells, these cells exhibited a reduced ability to survive inIxodes scapularisticks. 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 ofpdeBincreases our understanding of the c-di-GMP signaling network in motility regulation and the life cycle ofB. burgdorferi.

scholarly journals Genetics and Regulation of Chitobiose Utilization inBorrelia burgdorferi

2001 ◽  
Vol 183 (19) ◽  
pp. 5544-5553 ◽  
Author(s):  
Kit Tilly ◽  
Abdallah F. Elias ◽  
Jennifer Errett ◽  
Elizabeth Fischer ◽  
Radha Iyer ◽  
...  
Keyword(s):  
Life Cycle ◽  
Borrelia Burgdorferi ◽  
Bacterial Growth ◽  
Growth Temperature ◽  
Culture Medium ◽  
Significant Proportion ◽  
Ixodid Tick ◽  
Nutrient Acquisition ◽  
Wild Type ◽  
Membrane Spanning

ABSTRACT Borrelia burgdorferi spends a significant proportion of its life cycle within an ixodid tick, which has a cuticle containing chitin, a polymer of N-acetylglucosamine (GlcNAc). TheB. burgdorferi celA, celB, andcelC genes encode products homologous to transporters for cellobiose and chitobiose (the dimer subunit of chitin) in other bacteria, which could be useful for bacterial nutrient acquisition during growth within ticks. We found that chitobiose efficiently substituted for GlcNAc during bacterial growth in culture medium. We inactivated the celB gene, which encodes the putative membrane-spanning component of the transporter, and compared growth of the mutant in various media to that of its isogenic parent. The mutant was no longer able to utilize chitobiose, while neither the mutant nor the wild type can utilize cellobiose. We propose renaming the three genes chbA,chbB, and chbC, since they probably encode a chitobiose transporter. We also found that thechbC gene was regulated in response to growth temperature and during growth in medium lacking GlcNAc.

scholarly journals Few vertebrate species dominate the Borrelia burgdorferi s.l. life cycle

2016 ◽  
Vol 11 (4) ◽  
pp. 043001 ◽  
Author(s):  
T R Hofmeester ◽  
E C Coipan ◽  
S E van Wieren ◽  
H H T Prins ◽  
W Takken ◽  
...  
Keyword(s):  
Life Cycle ◽  
Borrelia Burgdorferi ◽  
Vertebrate Species ◽  
Borrelia Burgdorferi S.L

scholarly journals Analysis of the Borrelia burgdorferi Cyclic-di-GMP-Binding Protein PlzA Reveals a Role in Motility and Virulence

2011 ◽  
Vol 79 (5) ◽  
pp. 1815-1825 ◽  
Author(s):  
Joshua E. Pitzer ◽  
Syed Z. Sultan ◽  
Yoshihiro Hayakawa ◽  
Gerry Hobbs ◽  
Michael R. Miller ◽  
...  
Keyword(s):  
Life Cycle ◽  
Borrelia Burgdorferi ◽  
Binding Protein ◽  
Survival Rates ◽  
Wild Type ◽  
Content Type ◽  
Infectious Dose ◽  
Swimming Pattern ◽  
Bacteria Inactivation ◽  
Mutant Cells

ABSTRACTThe cyclic-dimeric-GMP (c-di-GMP)-binding protein PilZ has been implicated in bacterial motility and pathogenesis. Although BB0733 (PlzA), the only PilZ domain-containing protein inBorrelia burgdorferi, was reported to bind c-di-GMP, neither its role in motility or virulence nor it's affinity for c-di-GMP has been reported. We determined that PlzA specifically binds c-di-GMP with high affinity (dissociation constant [Kd], 1.25 μM), consistent withKdvalues reported for c-di-GMP-binding proteins from other bacteria. Inactivation of the monocistronically transcribedplzAresulted in an opaque/solid colony morphology, whereas the wild-type colonies were translucent. While the swimming pattern of mutant cells appeared normal, on swarm plates, mutant cells exhibited a significantly reduced swarm diameter, demonstrating a role ofplzAin motility. Furthermore, theplzAmutant cells were significantly less infectious in experimental mice (as determined by 50% infectious dose [ID50]) relative to wild-type spirochetes. The mutant also had survival rates in fed ticks lower than those of the wild type. Consequently,plzAmutant cells failed to complete the mouse-tick-mouse infection cycle, indicatingplzAis essential for the enzootic life cycle ofB. burgdorferi. All of these defects were corrected when the mutant was complemented incis. We propose that failure ofplzAmutant cells to infect mice was due to altered motility; however, the possibility that an unidentified factor(s) contributed to interruption of theB. burgdorferienzootic life cycle cannot yet be excluded.

scholarly journals Activation of the RpoN-RpoS regulatory pathway during the enzootic life cycle of Borrelia burgdorferi

2012 ◽  
Vol 12 (1) ◽  
pp. 44 ◽  
Author(s):  
Zhiming Ouyang ◽  
Sukanya Narasimhan ◽  
Girish Neelakanta ◽  
Manish Kumar ◽  
Utpal Pal ◽  
...  
Keyword(s):  
Life Cycle ◽  
Borrelia Burgdorferi ◽  
Regulatory Pathway

scholarly journals Motility Is Crucial for the Infectious Life Cycle of Borrelia burgdorferi

2013 ◽  
Vol 81 (6) ◽  
pp. 2012-2021 ◽  
Author(s):  
Syed Z. Sultan ◽  
Akarsh Manne ◽  
Philip E. Stewart ◽  
Aaron Bestor ◽  
Patricia A. Rosa ◽  
...  
Keyword(s):  
Life Cycle ◽  
Borrelia Burgdorferi ◽  
Mammalian Host ◽  
Major Protein ◽  
Content Type ◽  
Absolute Requirement ◽  
Wave Morphology ◽  
Minor Protein ◽  
Periplasmic Flagella ◽  
First Time

ABSTRACTThe Lyme disease spirochete,Borrelia burgdorferi, exists in a zoonotic cycle involving an arthropod tick and mammalian host. Dissemination of the organism within and between these hosts depends upon the spirochete's ability to traverse through complex tissues. Additionally, the spirochete outruns the host immune cells while migrating through the dermis, suggesting the importance ofB. burgdorferimotility in evading host clearance.B. burgdorferi's periplasmic flagellar filaments are composed primarily of a major protein, FlaB, and minor protein, FlaA. By constructing aflaBmutant that is nonmotile, we investigated for the first time the absolute requirement for motility in the mouse-tick life cycle ofB. burgdorferi. We found that whereas wild-type cells are motile and have a flat-wave morphology, mutant cells were nonmotile and rod shaped. These mutants were unable to establish infection in C3H/HeN mice via either needle injection or tick bite. In addition, these mutants had decreased viability in fed ticks. Our studies provide substantial evidence that the periplasmic flagella, and consequently motility, are critical not only for optimal survival in ticks but also for infection of the mammalian host by the arthropod tick vector.

scholarly journals Borrelia burgdorferi CheD Promotes Various Functions in Chemotaxis and the Pathogenic Life Cycle of the Spirochete

2016 ◽  
Vol 84 (6) ◽  
pp. 1743-1752 ◽  
Author(s):  
Ki Hwan Moon ◽  
Gerry Hobbs ◽  
M. A. Motaleb
Keyword(s):  
Life Cycle ◽  
Borrelia Burgdorferi ◽  
Phosphatase Activity ◽  
Response Regulator ◽  
Wild Type ◽  
Content Type ◽  
Mouse Infection ◽  
Protein Receptors ◽  
Chemotaxis Proteins

Borrelia burgdorferipossesses a sophisticated chemotaxis signaling system; however, the roles of the majority of the chemotaxis proteins in the infectious life cycle have not yet been demonstrated. Specifically, the role of CheD during host colonization has not been demonstrated in any bacterium. Here, we systematically characterized theB. burgdorferiCheD homolog using genetics and biochemical and mouse-tick-mouse infection cycle studies.Bacillus subtilisCheD plays an important role in chemotaxis by deamidation of methyl-accepting chemotaxis protein receptors (MCPs) and by increasing the receptor kinase activity or enhancing CheC phosphatase activity, thereby regulating the levels of the CheY response regulator. Our biochemical analysis indicates thatB. burgdorferiCheD significantly enhances CheX phosphatase activity by specifically interacting with the phosphatase. Moreover, CheD specifically binds two of the six MCPs, indicating that CheD may also modulate the receptor proteins. Although the motility of thecheDmutant cells was indistinguishable from that of the wild-type cells, the mutant did exhibit reduced chemotaxis. Importantly, the mutant showed significantly reduced infectivity in C3H/HeN mice via needle inoculation. Mouse-tick-mouse infection assays indicated that CheD is dispensable for acquisition or transmission of spirochetes; however, the viability ofcheDmutants in ticks is marginally reduced compared to that of the wild-type or complementedcheDspirochetes. These data suggest that CheD plays an important role in the chemotaxis and pathogenesis ofB. burgdorferi. We propose potential connections between CheD, CheX, and MCPs and discuss how these interactions play critical roles during the infectious life cycle of the spirochete.

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