Modification of Borrelia burgdorferi to overproduce OspA or VlsE alters its infectious behaviour

Xu, Qilong; McShan, Kristy; Liang, Fang Ting

doi:10.1099/mic.0.2008/019737-0

Cited by 16 publications

(23 citation statements)

References 44 publications

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“…Bacteria were injected into the dermis of the chest so skin specimens from the back were harvested as remote sites. As a positive control, the Δ dbpAB / dbpAB /1 and Δ dbpAB / dbpAB /2 bacteria were grown from 6 joint, 5 remote skin, and 2 heart specimens of 6 examined mice at 1 week; all sites became culture-positive at 2 weeks after inoculation (Table 2), consistent with our previous study that showed the parental clone 13A carrying pBBE22 colonized these tissues within 2 weeks [22]. The Δ dbpAB / dbpA' /1 and Δ dbpAB / dbpA' /2 bacteria were grown from 6 joint, 4 remote skin and 2 heart specimens of 6 examined mice at 1 week, and from 6 joint, 5 remote skin and 3 heart specimens of 6 mice at 2 weeks; all sites became culture-positive at 3 weeks.…”

Section: Resultssupporting

confidence: 84%

Common and Unique Contributions of Decorin-Binding Proteins A and B to the Overall Virulence of Borrelia burgdorferi

Shi

Seemanaplli

et al. 2008

PLoS ONE

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As an extracellular bacterium, the Lyme disease spirochete Borrelia burgdorferi resides primarily in the extracellular matrix and connective tissues and between host cells during mammalian infection, where decorin and glycosaminoglycans are abundantly found, so its interactions with these host ligands potentially affect various aspects of infection. Decorin-binding proteins (Dbps) A and B, encoded by a 2-gene operon, are outer surface lipoproteins with similar molecular weights and share approximately 40% identity, and both bind decorin and glycosaminoglycans. To investigate how DbpA and DbpB contribute differently to the overall virulence of B. burgdorferi, a dbpAB mutant was modified to overproduce the adhesins. Overproduction of either DbpA or DbpB resulted in restoration of the infectivity of the mutant to the control level, measured by 50% infectious dose (ID50), indicating that the two virulence factors are interchangeable in this regard. Overproduction of DbpA also allowed the mutant to disseminate to some but not all distal tissues slightly slower than the control, but the mutant with DbpB overproduction showed severely impaired dissemination to all tissues that were analyzed. The mutant with DbpA overproduction colonized all tissues, albeit generating bacterial loads significantly lower than the control in heart and joint, while the mutant overproducing DbpB remained severely defective in heart colonization and registered bacterial loads substantially lower than the control in joint. Taken together, the study indicated that DbpA and DbpB play a similar role in contribution to infectivity as measured by ID50 value but contribute differently to dissemination and tissue colonization.

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Section: Resultssupporting

confidence: 84%

Common and Unique Contributions of Decorin-Binding Proteins A and B to the Overall Virulence of Borrelia burgdorferi

Shi

Seemanaplli

et al. 2008

PLoS ONE

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“…Previous studies suggested that increased expression of dbpA and vlsE impaired dissemination, which resulted in quick clearance of spirochete from mice (56,57). We speculate that the repression of gene transcription through ptsG may have physiological importance under certain environmental conditions.…”

Section: Discussionmentioning

confidence: 96%

Phosphoenolpyruvate Phosphotransferase System Components Modulate Gene Transcription and Virulence of Borrelia burgdorferi

et al. 2016

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The phosphoenolpyruvate phosphotransferase system (PEP-PTS) and adenylate cyclase (AC) IV (encoded by BB0723 [cyaB]) are well conserved in different species of Borrelia. However, the functional roles of PEP-PTS and AC in the infectious cycle of Borrelia have not been characterized previously. We examined 12 PEP-PTS transporter component mutants by needle inoculation of mice to assess their ability to cause mouse infection. Transposon mutants with mutations in the EIIBC components (ptsG) (BB0645, thought to be involved in glucose-specific transport) were unable to cause infection in mice, while all other tested PEP-PTS mutants retained infectivity. Infectivity was partially restored in an in trans-complemented strain of the ptsG mutant. While the ptsG mutant survived normally in unfed as well as fed ticks, it was unable to cause infection in mice by tick transmission, suggesting that the function of ptsG is essential to establish infection by either needle inoculation or tick transmission. In Gramnegative organisms, the regulatory effects of the PEP-PTS are mediated by adenylate cyclase and cyclic AMP (cAMP) levels. A recombinant protein encoded by B. burgdorferi BB0723 (a putative cyaB homolog) was shown to have adenylate cyclase activity in vitro; however, mutants with mutations in this gene were fully infectious in the tick-mouse infection cycle, indicating that its function is not required in this process. By transcriptome analysis, we demonstrated that the ptsG gene may directly or indirectly modulate gene expression of Borrelia burgdorferi. Overall, the PEP-PTS glucose transporter PtsG appears to play important roles in the pathogenesis of B. burgdorferi that extend beyond its transport functions.

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“…Lp6.6 is subsurface lipoprotein (Katona et al , 1992) that lacks a detectable antibody response in infected hosts (Lahdenne et al , 1997). Previous studies determined that over-expression of vector-specific borrelial genes in mice, such as ospA , by genetically manipulated isolates, induces robust and specific borreliacidal antibodies that severely impact B. burgdorferi persistence (Strother et al , 2007; Xu et al , 2008). However, continual lp6.6 expression by complemented mutants within the murine host did not significantly influence spirochete persistence (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Borrelia burgdorferi small lipoprotein Lp6.6 is a member of multiple protein complexes in the outer membrane and facilitates pathogen transmission from ticks to mice

Promnares

Kumar

Shroder

et al. 2009

Molecular Microbiology

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Borrelia burgdorferi lipoprotein Lp6.6 is a differentially produced spirochete antigen. An assessment of lp6.6 expression covering representative stages of the infectious cycle of spirochetes demonstrates that the gene is solely expressed during pathogen persistence in ticks. Deletion of lp6.6 in infectious B. burgdorferi did not influence in vitro growth, or its ability to persist and induce inflammation in mice, migrate to larval or nymphal ticks or survive through the larval-nymphal molt. However, Lp6.6-deficient spirochetes displayed significant impairment in their ability to transmit from infected ticks to naïve mice, which was restored upon genetic complementation of the mutant with a wild-type copy of lp6.6, establishing that Lp6.6 plays a role in pathogen transmission from ticks to mammals. Lp6.6 is a subsurface, yet highly abundant, outer membrane antigen. Two-dimensional blue native/SDS-PAGE coupled with liquid chromatography-mass spectrometry (LC-MS/MS) analysis and protein cross-linking studies independently shows that Lp6.6 exists in multiple protein complexes in the outer membrane. We speculate that the function of Lp6.6 is connected to the physiological processes of these membrane complexes. Further characterization of differentially produced membrane antigens and associated protein complexes will likely aid in our understanding of the molecular details of B. burgdorferi persistence and transmission through a complex enzootic cycle.

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Modification of Borrelia burgdorferi to overproduce OspA or VlsE alters its infectious behaviour

Cited by 16 publications

References 44 publications

Common and Unique Contributions of Decorin-Binding Proteins A and B to the Overall Virulence of Borrelia burgdorferi

Common and Unique Contributions of Decorin-Binding Proteins A and B to the Overall Virulence of Borrelia burgdorferi

Phosphoenolpyruvate Phosphotransferase System Components Modulate Gene Transcription and Virulence of Borrelia burgdorferi

Borrelia burgdorferi small lipoprotein Lp6.6 is a member of multiple protein complexes in the outer membrane and facilitates pathogen transmission from ticks to mice

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