CsrA Modulates Levels of Lipoproteins and Key Regulators of Gene Expression Critical for Pathogenic Mechanisms of
            <i>Borrelia burgdorferi</i>

Karna, S. L. Rajasekhar; Sanjuán, Eva; Esteve-Gassent, Maria D.; Miller, Christine L.; Maruskova, Mahulena; Seshu, J.

doi:10.1128/iai.00882-10

Cited by 61 publications

(98 citation statements)

References 102 publications

(136 reference statements)

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“…2C, mt, lane 2) than in the parental or complemented strains (Fig. 2C, wt, ct, lane 2) (41). The levels of these regulators, as expected, were barely detectable in all three strains when propagated at the unfed-tick midgut conditions (Fig.…”

Section: Resultsmentioning

confidence: 80%

“…Notably, deletion of csrA Bb leads to a reduction in the levels of expression of several members of the rpoS regulon. Consistent with this in vitro phenotype, the csrA Bb mutant was attenuated for infection in the murine model of Lyme disease (41,82,88). Molecular determinants that connect the external environment to the metabolic status of B. burgdorferi that eventually lead to host-specific adaptation are yet to be characterized in detail.…”

mentioning

confidence: 69%

“…Whole-cell lysates were prepared and separated on SDS-12.5% PAGE gels as described previously (72). The separated proteins were either visualized by Coomassie brilliant blue staining or transferred to polyvinylidene difluoride (PVDF) membranes and subjected to immunoblot analysis as described previously (26,41,50,70). The membranes were probed with ␣-OspA monoclonal antibodies, ␣-BBA34, ␣-BBK32, ␣-DbpA, ␣-SodA, ␣-P66, ␣-BBA64, ␣-BosR, ␣-CsrA Bb , ␣-RpoS, and ␣-NapA antibodies.…”

Section: Methodsmentioning

confidence: 99%

“…9 as to how the concentration of acetyl phosphate or acetyl-CoA could contribute to the activation or dampening of the regulatory pathways for vertebrate host-specific adaptation in B. burgdorferi (27). We and others have recently shown that CsrA Bb is one of the key regulators involved in modulating vertebrate host-specific gene expression (41,70,82). While the deletion of csrA Bb reduced the levels of RpoS, BosR, and several virulence-related proteins, overexpression of CsrA Bb , on the other hand, increased levels of these proteins.…”

Section: Figmentioning

confidence: 99%

“…The accumulation of this metabolite is partly dependent on the repression of levels of an enzyme, phosphate acetyltransferase (Pta), which converts acetyl phosphate to acetyl-coenzyme A (CoA), leading to conditions that could potentially dampen the activation of the Rrp2-RpoNRpoS pathway. The repression of Pta has been shown to be mediated by CsrA Bb (carbon storage regulator A of B. burgdorferi), which we and others recently demonstrated plays a crucial role in affecting differential gene expression in B. burgdorferi that facilitates adaptation to vertebrate host-specific conditions (41,70,82). Notably, deletion of csrA Bb leads to a reduction in the levels of expression of several members of the rpoS regulon.…”

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confidence: 99%

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Oligopeptide Permease A5 Modulates Vertebrate Host-Specific Adaptation of Borrelia burgdorferi

et al. 2011

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Borrelia burgdorferi, the agent of Lyme disease, undergoes rapid adaptive gene expression in response to signals unique to its arthropod vector or vertebrate hosts. Among the upregulated genes under vertebrate host conditions is one of the five annotated homologs of oligopeptide permease A (OppA5, BBA34). A mutant lacking oppA5 was constructed in an lp25-deficient isolate of B. burgdorferi strain B31, and the minimal regions of infectivity were restored via a shuttle vector pBBE22 with or without an intact copy of bba34. Immunoblot analysis of the bba34 mutant revealed a reduction in the levels of RpoS, BosR, and CsrA Bb with a concomitant reduction in the levels of OspC, DbpA, BBK32, and BBA64. There were no changes in the levels of OspA, NapA, P66, and three other OppA orthologs. Quantitative transcriptional analysis correlated with the changes in the protein levels. However, the bba34 mutant displayed comparable infectivities in the C3H/HeN mice and the wild-type strain, despite the reduction in several pathogenesis-related proteins. Supplementation of the growth medium with increased levels of select components, notably sodium acetate and sodium bicarbonate, restored the levels of several proteins in the bba34 mutant to wild-type levels. We speculate that the transport of acetate appears to contribute to the accumulation of key metabolites, like acetyl phosphate, that facilitate the adaptation of B. burgdorferi to the vertebrate host by the activation of the Rrp2-RpoN-RpoS pathway. These studies underscore the importance of solute transport to host-specific adaptation of B. burgdorferi.

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Section: Resultsmentioning

confidence: 80%

mentioning

confidence: 69%

Section: Methodsmentioning

confidence: 99%

Section: Figmentioning

confidence: 99%

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confidence: 99%

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Oligopeptide Permease A5 Modulates Vertebrate Host-Specific Adaptation of Borrelia burgdorferi

et al. 2011

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Transformation of Borrelia burgdorferi

2021

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Transformation techniques used to genetically manipulate Borrelia burgdorferi, the agent of Lyme disease, play a critical role in generating mutants that facilitate analyses of the role of genes in the pathophysiology of this bacterium. A number of borrelial mutants have been successfully isolated and characterized since the first electrotransformation procedure was established 25 years ago (Samuels, 1995). This article is directed at additional considerations for transforming infectious B. burgdorferi to generate strains retaining the plasmid profile of the parental strain, enabling analysis of transformants for in vitro and in vivo phenotypes. These methods are built on previously published protocols and are intended to add steps and tips to enhance transformation efficiency and recovery of strains amenable for studies involving colonization, survival, and transmission of B. burgdorferi during the vector and vertebrate phases of infection.

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Regulation of Gene and Protein Expression in the Lyme Disease Spirochete

Stevenson

Seshu

2017

Current Topics in Microbiology and Immunology

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The infectious cycle of Borrelia burgdorferi necessitates persistent infection of both vertebrates and ticks, and efficient means of transmission between those two very different types of hosts. The Lyme disease spirochete has evolved mechanisms to sense its location in the infectious cycle, and use that information to control production of the proteins and other factors required for each step. Numerous components of borrelial regulatory pathways have been characterized to date. Their effects are being pieced together, thereby providing glimpses into a complex web of cooperative and antagonistic interactions. In this chapter, we present a broad overview of B. burgdorferi gene and protein regulation during the natural infectious cycle, discussions of culture-based methods for elucidating regulatory mechanisms, and summaries of many of the known regulatory proteins and small molecules. We also highlight areas that are in need of substantially more research.

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CsrA Modulates Levels of Lipoproteins and Key Regulators of Gene Expression Critical for Pathogenic Mechanisms of Borrelia burgdorferi

Cited by 61 publications

References 102 publications

Oligopeptide Permease A5 Modulates Vertebrate Host-Specific Adaptation of Borrelia burgdorferi

Oligopeptide Permease A5 Modulates Vertebrate Host-Specific Adaptation of Borrelia burgdorferi

Transformation of Borrelia burgdorferi

Regulation of Gene and Protein Expression in the Lyme Disease Spirochete

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