Regulators of Expression of the Oligopeptide Permease A Proteins of
            <i>Borrelia burgdorferi</i>

Medrano, Melisa S.; Ding, Yifeng; Wang, Xingguo; Lü, Peng; Coburn, Jenifer; Hu, Linden T.

doi:10.1128/jb.01760-06

Cited by 50 publications

(75 citation statements)

References 27 publications

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“…We (17,19) along with others (13,84) have proposed that the poly(T) tracts shared by both bba74 and ospA represent a candidate repressor binding site. ospE is thought to be regulated, in part, by EbfC, a chromosomally encoded YbaB DNA binding protein ortholog (55) induced during tick feeding and murine infection (5,59). The absence of EbfC recognition sites (TGTAACA) within the bba74 upstream region leads us to predict that bba74 and ospE are regulated differently despite the fact that both are downregulated within flat nymphs and induced during the nymphal blood meal.…”

Section: Discussionmentioning

confidence: 98%

“…Seminal studies by Norgard and coworkers (42,83,103) demonstrated that expression of RpoS is regulated by RpoN in concert with the response regulator protein Rrp2. Expression of RpoS, in turn, is essential for the induction of the established virulence factors ospC, dbpBA, and bbk32 as well as numerous other genes thought to be required to establish mammalian infection (18,19,42,59,79,80,100). Analysis of rpoS and RpoS-dependent genes within infected ticks has demonstrated that induction of the RpoS regulon begins during the nymphal blood meal prior to spirochete transmission (i.e., the RpoS-ON state) (19,35,36,39,41,76,77).…”

mentioning

confidence: 99%

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Borrelia burgdorferi bba74Is Expressed Exclusively during Tick Feeding and Is Regulated by Both Arthropod- and Mammalian Host-Specific Signals

Mulay¹,

Caimano²,

Iyer

et al. 2009

J Bacteriol

117

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Although BBA74 initially was described as a 28-kDa virulence-associated outer-membrane-spanning protein with porin-like function, subsequent studies revealed that it is periplasmic and downregulated in mammalian host-adapted spirochetes. To further elucidate the role of this protein in the Borrelia burgdorferi tick-mammal cycle, we conducted a thorough examination of its expression profile in comparison with the profiles of three well-characterized, differentially expressed borrelial genes (ospA, ospC, and ospE) and their proteins. In vitro, transcripts for bba74 were expressed at 23°C and further enhanced by a temperature shift (37°C), whereas BBA74 protein diminished at elevated temperatures; in contrast, neither transcript nor protein was expressed by spirochetes grown in dialysis membrane chambers (DMCs). Primer extension of wild-type B. burgdorferi grown in vitro, in conjunction with expression analysis of DMC-cultivated wild-type and rpoS mutant spirochetes, revealed that, like ospA, bba74 is transcribed by 70 and is subject to RpoS-mediated repression within the mammalian host. A series of experiments utilizing wild-type and rpoS mutant spirochetes was conducted to determine the transcriptional and translational profiles of bba74 during the tick-mouse cycle. Results from these studies revealed (i) that bba74 is transcribed by 70 exclusively during the larval and nymphal blood meals and (ii) that transcription of bba74 is bracketed by RpoS-independent and -dependent forms of repression that are induced by arthropod-and mammalian host-specific signals, respectively. Although loss of BBA74 does not impair the ability of B. burgdorferi to complete its infectious life cycle, the temporal compartmentalization of this gene's transcription suggests that BBA74 facilitates fitness of the spirochete within a narrow window of its tick phase. A reexamination of the paradigm for reciprocal regulation of ospA and ospC, performed herein, revealed that the heterogeneous expression of OspA and OspC displayed by spirochete populations during the nymphal blood meal results from the intricate sequence of transcriptional and translational changes that ensue as B. burgdorferi transitions between its arthropod vector and mammalian host.Lyme disease, the most common arthropod-borne infection in the United States, is caused by the spirochete Borrelia burgdorferi (87). In nature, B. burgdorferi has an obligate biannual enzootic cycle involving small mammalian host reservoirs, typically Peromyscus leucopus, and an Ixodes tick vector (51, 96). To successfully complete this life cycle, B. burgdorferi must adapt to and propagate within two markedly different physiologic milieus (67,75,96). A number of investigators have reported that manipulation of parameters, such as temperature, pH, DNA supercoiling, cell density, and partial O 2 pressure, during in vitro cultivation can trigger changes in gene and protein expression resembling those that occur when spirochetes adapt to their mammalian host (4,20,21,44,45,65,74,77,78,89,102). It als...

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Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

Borrelia burgdorferi bba74Is Expressed Exclusively during Tick Feeding and Is Regulated by Both Arthropod- and Mammalian Host-Specific Signals

Mulay¹,

Caimano²,

Iyer

et al. 2009

J Bacteriol

117

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“…Similarly, many B. burgdorferi genes encoding proteins with various putative physiological functions were induced by Rrp2, RpoN and RpoS; these genes included bb0251 (leuS), bb0777 (apt), bbk17 (adeC), bb0257 (cell division), bb0842 (arcB), bb0329 (oppA-2), bba34 (oppAV), bb0313 (ftsJ), bb0797 (mutS), bb0637 (nhaC-1), bbd20 (transposase), bb0646 (hydrolase), bb0728 (nox) and bb0729 (gltP) (Fraser et al, 1997). Among these genes, bb0329 and bba34 encode two putative periplasmic oligopeptide-binding proteins, which facilitate the transport of small peptides and essential amino acids (Fraser et al, 1997;Medrano et al, 2007). In addition, bb0728 and bb0729 are presumed to form an operon involved in the uptake of the amino acid glutamate (Fraser et al, 1997).…”

Section: Genes Regulated By Rrp2 Rpon and Rposmentioning

confidence: 99%

Transcriptional interplay among the regulators Rrp2, RpoN and RpoS in Borrelia burgdorferi

2008

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The RpoN-RpoS alternative sigma factor pathway is essential for key adaptive responses by Borrelia burgdorferi, particularly those involved in the infection of a mammalian host. A putative response regulator, Rrp2, is ostensibly required for activation of the RpoN-dependent transcription of rpoS. However, questions remain regarding the extent to which the three major constituents of this pathway (Rrp2, RpoN and RpoS) act interdependently. To assess the functional interplay between Rrp2, RpoN and RpoS, we employed microarray analyses to compare gene expression levels in rrp2, rpoN and rpoS mutants of parental strain 297. We identified 98 genes that were similarly regulated by Rrp2, RpoN and RpoS, and an additional 47 genes were determined to be likely regulated by this pathway. The substantial overlap between genes regulated by RpoS and RpoN provides compelling evidence that these two alternative sigma factors form a congruous pathway and that RpoN regulates B. burgdorferi gene expression through RpoS. Although several known B. burgdorferi virulence determinants were regulated by the RpoN-RpoS pathway, a defined function has yet to be ascribed to most of the genes substantially regulated by Rrp2, RpoN and RpoS.

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“…BpaB and EbfC compete with each other for binding to erp operator DNA (13). Like the erp genes, ebfC is poorly expressed in unfed ticks but significantly induced during tick feeding and during mammalian infection (44). For the present work, independent in vivo and in vitro studies were performed to determine the effects of these two proteins on Erp expression.…”

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confidence: 99%

BpaB and EbfC DNA-Binding Proteins Regulate Production of the Lyme Disease Spirochete's Infection-Associated Erp Surface Proteins

et al. 2012

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Successful infection of a host requires that the invading pathogen control its production of virulence determinants. The infectious agent must sense its environment and respond by increasing production of appropriate factors and repressing production of unnecessary ones. These features are especially critical for vector-borne pathogens, which must not only efficiently infect two extremely different host types but also be transmitted back and forth between hosts. Deciphering the regulatory pathways used by pathogens to control production of infection-associated proteins provides significant insight into the infectious nature of those organisms. Moreover, regulatory factors are attractive candidates for development of novel preventative and curative therapies.The spirochetal bacterium Borrelia burgdorferi, the agent of Lyme disease, is an excellent model organism for the study of gene regulation by a vector-borne pathogen. B. burgdorferi is genetically tractable, and its natural mammal-tick infectious cycle can be replicated in the laboratory. In addition, infection by B. burgdorferi is a significant cause of human morbidity, being the most commonly reported vector-borne disease in the United States and many other parts of the world (51, 55, 56).B. burgdorferi Erp lipoproteins are produced throughout mammalian infection but are largely repressed during colonization of vector ticks (10,31,48,49). Erp synthesis is greatly enhanced when B. burgdorferi is transmitted from a feeding tick into a warm-blooded host. Regulation of Erp protein production is controlled at the level of transcription (6). Erp proteins are located in the bacterial outer membrane and are exposed to the external environment (25,32,41). Known functions of Erp proteins include binding of host plasmin(ogen), laminin, and the complement regulators factor H and factor H-related proteins 1, 2, and 5 (2,3,11,12,34,37,40,45,59). These functions indicate roles for Erp proteins in host adherence, dissemination, and resistance to the alternative pathway of complement-mediated killing. Borrelial erp genes are located in mono-or bicistronic operons on extrachromosomal cp32 prophages, most of which replicate autonomously as circular episomes (24,60,63,64,72). Individual Lyme spirochetes naturally contain numerous different cp32 elements, each with a unique erp locus, and therefore produce multiple, distinct Erp surface proteins. A bacterium simultaneously expresses its entire repertoire of Erp proteins (26).A highly conserved DNA region immediately 5= of all erp promoters, the erp operator, is required for regulation of erp transcription (see Fig. 1) (6,10,64). Two erp operator-binding proteins have been identified, and their binding sites have been characterized: BpaB (borrelial plasmid ParB analogue) and EbfC (erp-binding factor, chromosomal) (4, 13, 52). BpaB binds with high affinity to a 5-bp sequence within the erp operator (13; C. A. Adams, unpublished). Binding of one BpaB protein to that sequence then facilitates binding of additional BpaB molecules al...

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Regulators of Expression of the Oligopeptide Permease A Proteins of Borrelia burgdorferi

Abstract: burgdorferi will help to identify coregulated proteins that may cooperate to allow the organism to survive in a specific environment.

Cited by 50 publications

References 27 publications

Borrelia burgdorferi bba74Is Expressed Exclusively during Tick Feeding and Is Regulated by Both Arthropod- and Mammalian Host-Specific Signals

Borrelia burgdorferi bba74Is Expressed Exclusively during Tick Feeding and Is Regulated by Both Arthropod- and Mammalian Host-Specific Signals

Transcriptional interplay among the regulators Rrp2, RpoN and RpoS in Borrelia burgdorferi

BpaB and EbfC DNA-Binding Proteins Regulate Production of the Lyme Disease Spirochete's Infection-Associated Erp Surface Proteins

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