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Journal of Bacteriology, November 2005, p. 7845-7852, Vol. 187, No. 22
0021-9193/05/$08.00+0     doi:10.1128/JB.187.22.7845-7852.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Alternate Sigma Factor RpoS Is Required for the In Vivo-Specific Repression of Borrelia burgdorferi Plasmid lp54-Borne ospA and lp6.6 Genes

Melissa J. Caimano,1*,{dagger} Christian H. Eggers,1,{dagger} Cynthia A. Gonzalez,1 and Justin D. Radolf1,2

Departments of Medicine,1 Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, Connecticut 060302

Received 11 July 2005/ Accepted 21 August 2005


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ABSTRACT
 
While numerous positively regulated loci have been characterized during the enzootic cycle of Borrelia burgdorferi, very little is known about the mechanism(s) involved in the repression of borrelial loci either during tick feeding or within the mammalian host. Here, we report that the alternative sigma factor RpoS is required for the in vivo-specific repression of at least two RpoD-dependent B. burgdorferi loci, ospA and lp6.6. The downregulation of ospA and Ip6.6 appears to require either a repressor molecule whose expression is RpoS dependent or an accessory factor which enables RpoS to directly interact with the ospA and Ip6.6 promoter elements, thereby blocking transcription by RpoD. The central role for RpoS during the earliest stages of host adaptation suggests that tick feeding imparts signals to spirochetes that trigger the RpoS-dependent repression, as well as expression, of in vivo-specific virulence factors critical for the tick-to-mammalian host transition.


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TEXT
 
In order to be sustained within its enzootic life cycle, Borrelia burgdorferi, the causative agent of Lyme disease, must be able to adapt to the nutritional, physiological, and immunological stresses associated with growth within two strikingly different milieus, the Ixodes tick vector and the mammalian host. Presumably, B. burgdorferi accomplishes this by being able to sense signaling cues associated with tick feeding and growth within the host. The response to these signals, in turn, triggers the expression of factors that enable spirochetes to migrate from the tick midgut to the salivary glands and then, ultimately, to disseminate from the tick feeding site to host target tissues. Not unexpectedly, the entry of a bloodmeal into a B. burgdorferi-infected tick is accompanied by extensive changes in the borrelial transcriptome and proteome, a process referred to as mammalian host adaptation (1, 4, 43). While a number of studies have demonstrated that the expression of many borrelial loci can be modulated by the manipulation of in vitro growth conditions (1, 2, 5, 8, 10, 11, 17, 27, 32, 41, 48, 51, 58, 60, 63-65, 68), we and others have shown that as-yet-undefined mammalian host-specific cues are essential for triggering the genetic program(s) underlying host adaptation (1, 2, 8, 18, 27, 32, 46, 49, 51, 52, 63, 64, 66).

The majority of previously published reports have focused on increased borrelial gene expression both in vitro and in the context of the mammalian host. Recent microarray analyses, however, suggest that the ability of B. burgdorferi to repress the expression of select loci may be equally critical to host adaptation and disease pathogenesis (8, 21, 38, 39, 51, 61). The contributions of transcriptional induction and repression in B. burgdorferi are well exemplified by the reciprocal synthesis of outer surface protein A (OspA) and OspC. As first described by Schwan et al. (56) and subsequently confirmed by others (14, 20, 37, 40), the marked downregulation of OspA during tick feeding is accompanied by the increased expression of OspC. The OspA/OspC dichotomy has been recognized for a number of years, but its biological significance has only recently come to light. While there is still some debate regarding its role within the tick (21, 24, 45), OspC appears to be required for the establishment of infection (24), and consequently, the expression of this lipoprotein must be initiated prior to transmission (24, 40). OspA, on the other hand, appears to interact with a tick receptor, TROSPA, to anchor the spirochete within the midgut (42, 44, 69). The repression of OspA, therefore, is likely critical for the migration of spirochetes from the midgut. Studies examining the expression of these two lipoprotein genes have suggested two distinct mechanisms for their regulation. Expression of ospC is dependent on RpoS and is positively regulated by the Rrp2/RpoN/RpoS signaling cascade (30, 67). ospA, in contrast, is believed to be transcribed via the housekeeping factor RpoD (also referred to as {sigma}70) (3, 59) and is negatively regulated by an unknown mechanism in response to in vivo-specific signals.

In this report, we provide evidence demonstrating that the RpoS-dependent pathway is required for the repression of at least two lp54-borne loci, ospA and lp6.6. The downregulation of ospA and Ip6.6 appears to require either a repressor molecule whose expression is RpoS dependent or an accessory factor which enables RpoS to directly interact with the ospA and lp6.6 promoter elements, thereby blocking transcription by RpoD. The central role for RpoS during the earliest stages of host adaptation suggests that tick feeding imparts signals to spirochetes that trigger the RpoS-dependent repression, as well as expression, of in vivo-specific virulence factors critical for the tick-to-mammalian host transition.

B. burgdorferi rpoS mutants fail to downregulate OspA and Lp6.6 in vivo. B. burgdorferi cultivated within dialysis membrane chambers (DMCs) implanted into the peritoneal cavities of small mammals (i.e., rats and rabbits) (1, 57) undergoes many of the antigenic and physiological changes associated with mammalian host adaptation (1, 8, 9, 18, 23, 26, 46, 49, 51, 52). Most notably, DMC-cultivated spirochetes express little to no OspA in addition to expressing significantly higher levels of a number of borrelial lipoproteins than their in vitro-grown counterparts (1, 8, 9, 51, 57). During the course of our earlier studies examining gene expression in B. burgdorferi rpoS mutants cultivated within DMCs (9), we observed that the rpoS mutant AH200 (30) (Table 1) not only failed to express known RpoS-dependent lipoproteins but, quite surprisingly, also failed to downregulate OspA in vivo (Fig. 1A); this phenotype also applied to OspB, which was present at equally high levels in in vitro- and DMC-cultivated AH200 (Fig. 1A). A closer inspection of the polypeptide profiles of B. burgdorferi wild-type and mutant DMC-cultivated spirochetes by silver stain analysis revealed other differences, particularly within the lower-molecular-mass region (>20 kDa) (Fig. 1A), suggesting that the changes associated with the loss of RpoS during growth in vivo are not limited to OspA.


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  		TABLE 1. Strains used in this study



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  		FIG. 1. B. burgdorferi rpoS and rpoN mutants fail to downregulate OspA in vivo. B. burgdorferi was cultivated in BSK-H medium at 23°C and following a temperature shift to 37°C and host adapted within DMCs (HA) as previously described (9). (A) Whole-cell lysates of the uncloned wild-type strain 297 (WT 297), rpoS mutant (AH200) (30), and rpoN mutant (AH231) (30) were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and then silver stained as previously described (9). (B) Whole-cell lysates (~107 per lane) for the wild-type clone CE162 (9, 16) and rpoS mutant clone CE174 (9, 16) were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and then either silver stained as previously described or immunoblotted using polyclonal sera directed against Lp6.6 (32), DbpA (25), OspE (1), or FlaB. Asterisks indicate the previously described truncated form of OspB (13). Molecular mass markers (kDa) are indicated.

Previous studies by Hubner et al. (30) have demonstrated that the transcription of rpoS requires a second alternate sigma factor, RpoN, and as a consequence, B. burgdorferi isolates lacking RpoN exhibit lipoprotein expression phenotypes associated with the loss of rpoS (e.g., lack of OspC and DbpA) (21, 30). Fisher et al. (21), on the other hand, have proposed that RpoN can independently transcribe a number of B. burgdorferi loci. Thus, it was of interest to examine how the abrogation of RpoN affects the regulation of OspA. As shown in Fig. 1A, AH231 (Table 1), a B. burgdorferi strain 297 RpoN mutant, also failed to express OspC and downregulate OspA during growth within DMCs, indicating that the involvement of RpoN in this process is likely indirect and mediated through RpoS. Given that the B. burgdorferi genome contains only three annotated sigma factors (rpoD, rpoN, and rpoS) (22), the constitutive expression of OspA in both the rpoN and rpoS mutants also provides direct evidence that the transcription of this locus is entirely RpoD dependent.

To confirm that the failure to downregulate OspA during growth within DMCs was due to the loss of RpoS and not the result of a secondary mutation, we endeavored to restore rpoS by complementation. Because AH200 is refractory to transformation (9, 30), we were unable to introduce the previously described plasmid complement, rpoS/pCE320 (9), into this mutant. We, therefore, regenerated the rpoS mutation by electroporating CE162 (Table 1), a highly transformable, virulent B. burgdorferi 297 clone (9, 16), with a 3-kb amplicon fragment of AH200 genomic DNA containing the rpoS::ermC inactivation cassette as previously described (9, 16). The resulting erythromycin-resistant transformants were screened by PCR amplification for the presence of the ermC cassette within the endogenous copy of rpoS using primers rpoS-5' and rpoS-3' (Table 2) as previously described (9). Five rpoS mutants from two independent transformations, confirmed to contain the mutant rpoS allele using PCR, lacked expression of OspC and decorin binding protein A (DbpA) during temperature shift in vitro and within DMCs and also failed to downregulate OspA during cultivation within DMCs; representative results from the analysis of one transformant, CE174 (Table 1), are shown in Fig. 1B. Previous studies have demonstrated that a second borrelial lipoprotein, Lp6.6 (BBA62), exhibits a similar, if not identical, expression pattern to that of OspA, including downregulation within DMCs (1, 8, 32). To determine whether downregulation of Lp6.6 was similarly RpoS dependent, we immunoblotted lysates prepared from CE162 (wild type [wt]) and CE174 (rpoS mutant) cultivated in vitro and within DMCs using antiserum specific for Lp6.6 (32). Indeed, wild-type CE162 constitutively expressed Lp6.6 in vitro, while little to no Lp6.6 was detectable following DMC cultivation. As with OspA, the rpoS mutant CE174 continued to express Lp6.6 during DMC cultivation at levels similar to those observed in vitro (Fig. 1B). The upregulation of OspE in both the rpoS (Fig. 1B) and rpoN (data not shown) mutants following temperature shift confirmed that these isolates retained the ability to differentially express RpoD-dependent loci and, moreover, suggests that the defects in differential gene expression associated with these mutations are limited to the RpoN/RpoS pathway. These findings complement those reported earlier by Roberts et al. (52) for the expression of the Bdr-paralogous family in the same rpoS and rpoN mutants.


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  		TABLE 2. Primers used in this study

Complementation with rpoS restores the repression of OspA and Lp6.6 in vivo. Unlike AH200, CE174 was readily transformed with the complementing plasmid rpoS/pCE320 (9). The restoration of RpoS activity in the complemented transformant, CE467 (Table 1), was confirmed by its ability to express OspC and DbpA to wild-type levels following temperature shift in vitro (Fig. 2). This isolate also recently was shown to have restored infectivity for mice (9). Next, we cultivated CE162 (wt), CE174 (rpoS mutant), and CE467 (complemented rpoS mutant) within DMCs; the complementation of CE174 with rpoS resulted in the downregulation of both OspA and Lp6.6 to near wild-type levels (Fig. 2). Given that rpoS is not required for growth and survival within DMCs (9), one potential explanation for the residual expression of OspA and Lp6.6 in CE467 is the spontaneous loss of the complementing plasmid due to the lack of selection pressure in vivo. We, therefore, assayed DMC-cultivated CE467 spirochetes for the presence of rpoS/pCE320 by solid-phase plating in the presence and absence of antibiotic selection (53). In contrast to the high rpoS/pCE320 retention rates observed in vitro (≥90%) under antibiotic selection, the complementing plasmid was present in only 60% of CE467 spirochetes following DMC explantation and subsequent solid-phase plating in the absence and presence of kanamycin. To circumvent these stability issues, we initially attempted to take advantage of B. burgdorferi's strict requirement for the plasmid lp25-encoded nicotinamidase (pncA) in vivo (49) by incorporating this locus into our pCE320 shuttle vector (15) and then transforming the resulting rpoS/pCE320+pncA plasmid into a variant of CE174 that had spontaneously lost the endogenous lp25 plasmid. While B. burgdorferi lacking lp25 is unable to survive in mice and within DMCs (18, 23, 49), we were surprised to find that (i) the addition of pncA conferred only a modest increase in the level of stability to the complementing plasmid in DMCs (data not shown) and that (ii) we were readily able to detect spirochetes lacking pncA following explantation (data not shown). Thus, while pncA is absolutely required to establish growth in vivo, once spirochetes make the physiological switch to growth within the mammalian host, the requirement for pncA appears to be markedly diminished or absent. It also is worth noting that Bockenstedt et al. (7) made a similar observation with antibiotic-treated mice.



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  		FIG. 2. Complementation with B. burgdorferi wild-type rpoS restores the downregulation of OspA and Lp6.6. Whole-cell lysates were prepared from the B. burgdorferi wild-type 297 strain CE162 (9, 16), the rpoS mutant CE174 (9, 16), and rpoS mutants complemented with wild-type rpoS on a circular plasmid (CE467) or on the chromosome (CE998) following a temperature shift in vitro (37°C) and within DMCs (HA). Lysate samples (~107 per lane) were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and then either silver stained or immunoblotted using polyclonal sera directed against Lp6.6 (32) or FlaB. Molecular mass markers (kDa) are indicated.

As an alternative to plasmid complementation, we employed a more technically challenging chromosomal complementation strategy by inserting a wild-type copy of rpoS, including the upstream promoter region (using primers listed in Table 2), into the chromosomally located ermC gene in CE174. Briefly, the erythromycin resistance gene (ermC) from pGK12 (62) was PCR amplified using primers ErmC1118R+BssHII and ErmC1F+BssHII and cloned into BssHII-digested pBSII SK+ (Stratagene, La Jolla, CA). The multiple cloning site was amplified from pBSII SK+ using the commercially available T3 and T7 primers with BclI ends and introduced back into the BclI site of ermC (pCE665). The PflgB::kan marker was amplified from pCE320 using the PflgBF+KpnI and kan3'R+KpnI primers and then cloned into the KpnI site in pCE665 to generate pCE671. Finally, the rpoS gene and 500-bp upstream region was PCR amplified using RpoS-5' and RpoS-3' (Table 2) and cloned into the pCR2.1-TOPO vector (Invitrogen, Carlsbad, CA). The rpoS-complementing fragment was then cloned into pCE671 in the opposite orientation of the kan marker using BamHI and NotI to generate pCE697. Ten micrograms of pCE697 was introduced into CE174 by electrotransformation (53), and kanamycin-resistant transformants were selected as previously described (9, 16). One clone, CE998, was selected, and the integration of wild-type rpoS into chromosomal ermC was confirmed by PCR and sequencing (data not shown). As shown in Fig. 2, the expression of Lp6.6 was completely abrogated in DMC-cultivated CE998. Interestingly, however, the expression of OspA was significantly reduced, but as with the plasmid complement CE467, residual expression was detected. Taken together, the results from both complementation approaches clearly demonstrate that the failure to downregulate OspA and Lp6.6 during DMC cultivation is due to the loss of RpoS. However, subtle differences as to how this regulatory pathway influences the downregulation of individual genes may exist.

Repression of ospA by RpoS occurs at the level of transcription initiation and does not require localization of promoter sequences to a linear plasmid. Previous studies demonstrating that ospA is regulated at the transcriptional level have been dependent upon the detection or measurement of steady-state levels of message by Northern blotting (29, 34, 50), reverse transcription-PCR (28, 33, 40, 47, 50), or microarray analysis (8, 38, 39, 41, 51, 61). Thus, in order to determine whether the effect of RpoS on ospA downregulation is due to decreased transcription initiation or mRNA degradation, we decided to use a transcriptional reporter construct that would enable us to discriminate between these two possibilities. The selection of green fluorescent protein (GFP) as the reporter, in conjunction with flow cytometry, has the additional advantage of enabling one to assess gene expression by individual spirochetes within a population (6, 12, 15, 16, 54). For these studies, a 189-bp region of the upstream sequence containing both the ospA promoter and a poly(T) tract reported to be involved in the regulation of ospA transcription in vitro (59) was cloned upstream of a promoterless gfp contained on our cp32-based shuttle vector pCE320 (15). The resulting construct, PospA-gfp (Table 1), was then transformed into both B. burgdorferi wild-type and rpoS mutant isolates and assayed by flow cytometry following temperature shift and growth within DMCs, as previously described (16). These data are summarized in Table 3, while representative flow cytograms and micrographs are shown in Fig. 3. PospA-gfp expression in DMC-cultivated wild-type CE103 was significantly decreased compared to the levels observed at 37°C in vitro. To ensure that this low level of fluorescence is due to the downregulation of the ospA promoter and not spontaneous loss of the reporter shuttle vector in the absence of selective pressure, we assayed for reporter plasmid retention in CE103 following explantation as described above. More than 60% of DMC-cultivated CE103 spirochetes retained the PospA-gfp reporter as determined by solid-phase plating in the presence and absence of antibiotic and fluorescence microscopy; even after plasmid loss was taken into account, CE103 still expressed dramatically less GFP with respect to the percentage of fluorescent spirochetes and their average mean fluorescence intensity (MFI) than their in vitro-grown counterparts (Table 3). In contrast, the levels of GFP in the rpoS mutant CE472 remained high during DMC cultivation (Fig. 3 and Table 3). Thus, taken together, these data confirmed the following: (i) the PospA-gfp reporter faithfully reproduces the expression pattern of the native gene; (ii) the effect of RpoS on ospA downregulation in vivo occurs at the level of transcription initiation; (iii) the upstream sequences which mediate this effect remain operative when removed from neighboring plasmid lp54 sequences; and (iv) ospA transcription is entirely RpoD dependent. Regarding the last point, we observed that during in vitro growth, PospA-gfp expression in the rpoS mutant was consistently greater than that in the wild-type background (Table 3). In addition to further reinforcing the importance of RpoD for ospA transcription, these data raise the intriguing possibility that sigma factor competition for a limiting amount of RNA polymerase apoenzyme (19) could play a role in the regulation of ospA by providing a passive framework for modulating the expression of this locus.


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  		TABLE 3. PospA-gfp fluorescence levels from spirochetes grown at 37°C and within DMCs



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  		FIG. 3. RpoS-mediated repression of ospA occurs at the level of transcription initiation. Analysis of the ospA promoter (PospA) in wild-type and rpoS mutant B. burgdorferi cells using a GFP reporter system. (Left panels) Samples from wild-type strain 297 (CE103) and an rpoS mutant (CE472) transformed with the PospA-gfp reporter constructs cultivated in vitro following a temperature shift from 23°C to 37°C and within DMCs (HA) were analyzed by flow cytometry as described previously (12). Spirochetes were identified by forward- and side-scatter profiles and by staining with the nucleic acid stain SYTO59 (y axis; Molecular Probes). GFP intensity is measured on the x axis. Wild-type B. burgdorferi transformed with the constitutively expressed PflaB-gfp (CE56) serves as a control. (Right panels) Dark-field and fluorescence microscopy images of spirochetes cultivated within DMCs.

Models for RpoS-dependent repression of B. burgdorferi loci in vivo. In this report, we demonstrate that RpoS is required for the repression, as well as the induction, of key borrelial virulence determinants during mammalian host adaptation. Two scenarios can be envisioned to explain this form of negative regulation (Fig. 4A). The first, and perhaps simplest, explanation is that RpoS controls the expression of a repressor molecule which in turn requires activation by some in vivo-signaling pathway in order to block transcription by RpoD. The existence of an ospA promoter repressor has been proposed in earlier studies (35, 36). Using a spontaneously occurring B. burgdorferi mutant that fails to express ospA in vitro, Margolis and Samuels (36) detected the binding of an unknown protein(s) to a region upstream of ospA in strain CA-11.2A that is almost identical to the sequence contained within our PospA reporter. In order for the same factor to be directly involved in the repression of both ospA and lp6.6, there must be common upstream sequences to which it can bind. It is worth noting, therefore, that sequences upstream of the lp6.6 structural gene contain a poly(T) tract similar to that upstream of ospA (Fig. 4B). An alternative model, which cannot be eliminated using the data currently in hand, proposes that an in vivo-activated accessory factor either modifies or directly interacts with RpoS. This modification or interaction enables the alternate sigma factor to bind to the ospA and lp6.6 promoters, thus blocking RpoD-dependent transcription, most likely by preventing the formation of an open complex at the promoter (Fig. 4A). For this regulatory mechanism to hold, a dramatic change in sigma factor recognition of the ospA promoter would have to occur. With either model, our finding that the presence of RpoS appears to diminish the RpoD-dependent expression of ospA is potentially significant because it suggests that ospA expression is subject to some constitutive level of basal inhibition and, as a consequence, is poised for repression. Support for this notion is provided by temporal studies demonstrating that the expression of ospA in B. burgdorferi-infected ticks is rapidly downregulated upon the acquisition of a bloodmeal (40, 55). Our prior studies have demonstrated that the expression of rpoS and RpoS-dependent genes occurs almost immediately after spirochetes enter exponential-phase growth following temperature shift (9); this rapid onset of RpoS-dependent gene expression presumably also occurs during the initial stages of spirochete expansion within B. burgdorferi-infected ticks. Thus, by integrating the alternate sigma factor RpoS into two distinct regulatory pathways involved in both the expression of OspC and the repression of OspA early during tick feeding, B. burgdorferi appears to have devised a strategy for ensuring the coordinated reciprocal regulation of these transmission-associated loci.



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  		FIG. 4. (A) Proposed models for RpoS-dependent in vivo repression of ospA and lp6.6. (Left panel) RpoS controls the expression of a repressor protein which, upon activation by in vivo signals, binds to the ospA and lp6.6 promoter regions, preventing subsequent transcription by the RpoD-containing RNAP holoenzyme. (Right panel) Modification by or association with an in vivo-specific accessory factor enables RpoS to bind to the ospA promoter and prevents the establishment of an open promoter complex, thereby blocking RpoD-dependent transcription initiation. Abbreviations: RNAP, RNA polymerase; Rrp2, response regulator 2; IRP, in vivo-specific repressor protein; AF, accessory factor; {sigma}s, RpoS; {sigma}70, RpoD. (B) Diagram of ospA and lp6.6 upstream promoter regions including a poly(T) tract (boxed). The transcriptional start site for ospA (31) is designated by an asterisk. Putative –10/–35 regions, ribosome binding sites (RBS), and methionine start codons (MET) are indicated.


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ACKNOWLEDGMENTS
 
This work was supported by grant AI-29735 from the Lyme disease program awarded by the National Institutes of Allergy and Infectious Diseases, National Institute of Health.

All experimental procedures using animals were performed in accordance with protocols and guidelines established by the Institutional Animal Care and Use Committee.


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FOOTNOTES
 
* Corresponding author. Mailing address: Department of Medicine, University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT 06030-3715. Phone: (860) 679-8390. Fax: (860) 679-1358. E-mail: mcaima{at}up.uchc.edu. Back

{dagger} M.J.C. and C.H.E. contributed equally to this work. Back


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REFERENCES
 
    1
  1. Akins, D. R., K. W. Bourell, M. J. Caimano, M. V. Norgard, and J. D. Radolf. 1998. A new animal model for studying Lyme disease spirochetes in a mammalian host-adapted state. J. Clin. Investig. 101:2240-2250.[Medline]
    2. 2
  2. Akins, D. R., S. F. Porcella, T. G. Popova, D. Shevchenko, S. I. Baker, M. Li, M. V. Norgard, and J. D. Radolf. 1995. Evidence for in vivo but not in vitro expression of a Borrelia burgdorferi outer surface protein F (OspF) homolog. Mol. Microbiol. 18:507-520.[CrossRef][Medline]
    3. 3
  3. Alverson, J., S. F. Bundle, C. D. Sohaskey, M. C. Lybecker, and D. S. Samuels. 2003. Transcriptional regulation of the ospAB and ospC promoters from Borrelia burgdorferi. Mol. Microbiol. 48:1665-1677.[CrossRef][Medline]
    4. 4
  4. Anguita, J., M. N. Hedrick, and E. Fikrig. 2003. Adaptation of Borrelia burgdorferi in the tick and the mammalian host. FEMS Microbiol. Rev. 27:493-504.[CrossRef][Medline]
    5. 5
  5. Babb, K., N. El-Hage, J. C. Miller, J. A. Carroll, and B. Stevenson. 2001. Distinct regulatory pathways control expression of Borrelia burgdorferi infection-associated OspC and Erp surface proteins. Infect. Immun. 69: 4146-4153.[Abstract/Free Full Text]
    6. 6
  6. Babb, K., J. D. McAlister, J. C. Miller, and B. Stevenson. 2004. Molecular characterization of Borrelia burgdorferi erp promoter/operator elements. J. Bacteriol. 186:2745-2756.[Abstract/Free Full Text]
    7. 7
  7. Bockenstedt, L. K., J. Mao, E. Hodzic, S. W. Barthold, and D. Fish. 2002. Detection of attenuated, noninfectious spirochetes in Borrelia burgdorferi-infected mice after antibiotic treatment. J. Infect. Dis. 186:1430-1437.[CrossRef][Medline]
    8. 8
  8. Brooks, C. S., P. S. Hefty, S. E. Jolliff, and D. R. Akins. 2003. Global analysis of Borrelia burgdorferi genes regulated by mammalian host-specific signals. Infect. Immun. 71:3371-3383.[Abstract/Free Full Text]
    9. 9
  9. Caimano, M. J., C. H. Eggers, K. R. O. Hazlett, and J. D. Radolf. 2004. RpoS is not central to the general stress response in Borrelia burgdorferi but does control expression of one or more essential virulence determinants. Infect. Immun. 72:6433-6445.[Abstract/Free Full Text]
    10. 10
  10. Carroll, J. A., R. M. Cordova, and C. F. Garon. 2000. Identification of 11 pH-regulated genes in Borrelia burgdorferi localizing to linear plasmids. Infect. Immun. 68:6677-6684.[Abstract/Free Full Text]
    11. 11
  11. Carroll, J. A., C. F. Garon, and T. G. Schwan. 1999. Effects of environmental pH on membrane proteins in Borrelia burgdorferi Infect. Immun. 67:3181-3187.[Abstract/Free Full Text]
    12. 12
  12. Carroll, J. A., P. E. Stewart, P. Rosa, A. F. Elias, and C. F. Garon. 2003. An enhanced GFP reporter system to monitor gene expression in Borrelia burgdorferi. Microbiology 149:1819-1828.[Abstract/Free Full Text]
    13. 13
  13. Coleman, J. L., R. C. Rogers, P. A. Rosa, and J. L. Benach. 1994. Variations in the ospB gene of Borrelia burgdorferi result in differences in monoclonal antibody reactivity and in production of escape variants. Infect. Immun. 62:303-307.[Abstract/Free Full Text]
    14. 14
  14. de Silva, A. M., S. R. Telford III, L. R. Brunet, S. W. Barthold, and E. Fikrig. 1996. Borrelia burgdorferi OspA is an arthropod-specific transmission-blocking Lyme disease vaccine. J. Exp. Med. 183:271-275.[Abstract/Free Full Text]
    15. 15
  15. Eggers, C. H., M. J. Caimano, M. L. Clawson, W. G. Miller, D. S. Samuels, and J. D. Radolf. 2002. Identification of loci critical for replication and compatibility of a Borrelia burgdorferi cp32 plasmid and use of a cp32-based shuttle vector for the expression of fluorescent reporters in the Lyme disease spirochaete. Mol. Microbiol. 43:281-295.[CrossRef][Medline]
    16. 16
  16. Eggers, C. H., M. J. Caimano, and J. D. Radolf. 2004. Analysis of promoter elements involved in the transcriptional initiation of RpoS-dependent Borrelia burgdorferi genes. J. Bacteriol. 186:7390-7402.[Abstract/Free Full Text]
    17. 17
  17. El-Hage, N., and B. Stevenson. 2002. Simultaneous coexpression of Borrelia burgdorferi Erp proteins occurs through a specific, erp locus-directed regulatory mechanism. J. Bacteriol. 184:4536-4543.[Abstract/Free Full Text]
    18. 18
  18. Elias, A. F., P. E. Stewart, D. Grimm, M. J. Caimano, C. H. Eggers, K. Tilly, J. L. Bono, D. R. Akins, J. D. Radolf, T. G. Schwan, and P. Rosa. 2002. Clonal polymorphism of Borrelia burgdorferi strain B31 MI: implications for mutagenesis in an infectious strain background. Infect. Immun. 70:2139-2150.[Abstract/Free Full Text]
    19. 19
  19. Farewell, A., K. Kvint, and T. Nystrom. 1998. Negative regulation by RpoS: a case of sigma factor competition. Mol. Microbiol. 29:1039-1051.[CrossRef][Medline]
    20. 20
  20. Fingerle, V., U. Hauser, G. Liegl, B. Petko, V. Preac-Mursic, and B. Wilske. 1995. Expression of outer surface proteins A and C of Borrelia burgdorferi in Ixodes ricinus. J. Clin. Microbiol. 33:1867-1869.[Abstract]
    21. 21
  21. Fisher, M. A., D. Grimm, A. K. Henion, A. F. Elias, P. E. Stewart, P. A. Rosa, and F. C. Gherardini. 2005. Borrelia burgdorferi {sigma}54 is required for mammalian infection and vector transmission but not for tick colonization. Proc. Natl. Acad. Sci. USA 102:5162-5167.[Abstract/Free Full Text]
    22. 22
  22. Fraser, C. M., S. Casjens, W. M. Huang, G. G. Sutton, R. Clayton, R. Lathigra, O. White, K. A. Ketchum, R. Dodson, E. K. Hickey, M. Gwinn, B. Dougherty, J. F. Tomb, R. D. Fleischmann, D. Richardson, J. Peterson, A. R. Kerlavage, J. Quackenbush, S. Salzberg, M. Hanson, R. van Vugt, N. Palmer, M. D. Adams, J. Gocayne, J. Weidman, T. Utterback, L. Watthey, L. McDonald, P. Artiach, C. Bowman, S. Garland, C. Fujii, M. D. Cotton, K. Horst, K. Roberts, B. Hatch, H. O. Smith, and J. C. Venter. 1997. Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi. Nature 390:580-586.[CrossRef][Medline]
    23. 23
  23. Grimm, D., C. H. Eggers, M. J. Caimano, K. Tilly, P. E. Stewart, A. F. Elias, J. D. Radolf, and P. A. Rosa. 2004. Experimental assessment of the roles of linear plasmids lp25 and lp28-1 of Borrelia burgdorferi throughout the infectious cycle. Infect. Immun. 72:5938-5946.[Abstract/Free Full Text]
    24. 24
  24. Grimm, D., K. Tilly, R. Byram, P. E. Stewart, J. G. Krum, D. M. Bueschel, T. G. Schwan, P. F. Policastro, A. F. Elias, and P. A. Rosa. 2004. Outer-surface protein C of the Lyme disease spirochete: a protein induced in ticks for infection of mammals. Proc. Natl. Acad. Sci. USA 101:3142-3147.[Abstract/Free Full Text]
    25. 25
  25. Hagman, K. E., P. Lahdenne, T. G. Popova, S. F. Porcella, D. R. Akins, J. D. Radolf, and M. V. Norgard. 1998. Decorin-binding protein of Borrelia burgdorferi is encoded within a two-gene operon and is protective in the murine model of Lyme borreliosis. Infect. Immun. 66:2674-2683.[Abstract/Free Full Text]
    26. 26
  26. Hefty, P. S., S. E. Jolliff, M. J. Caimano, S. K. Wikel, and D. R. Akins. 2002. Changes in temporal and spatial patterns of outer surface lipoprotein expression generate population heterogeneity and antigenic diversity in the Lyme disease spirochete, Borrelia burgdorferi. Infect. Immun. 70:3468-3478.[Abstract/Free Full Text]
    27. 27
  27. Hefty, P. S., S. E. Jolliff, M. J. Caimano, S. K. Wikel, J. D. Radolf, and D. R. Akins. 2001. Regulation of OspE-related, OspF-related, and Elp lipoproteins of Borrelia burgdorferi strain 297 by mammalian host-specific signals. Infect. Immun. 69:3618-3627.[Abstract/Free Full Text]
    28. 28
  28. Hodzic, E., S. Feng, K. J. Freet, and S. W. Barthold. 2003. Borrelia burgdorferi population dynamics and prototype gene expression during infection of immunocompetent and immunodeficient mice. Infect. Immun. 71:5042-5055.[Abstract/Free Full Text]
    29. 29
  29. Howe, T. R., F. W. LaQuier, and A. G. Barbour. 1986. Organization of genes encoding two outer membrane proteins of the Lyme disease agent Borrelia burgdorferi within a single transcriptional unit. Infect. Immun. 54:207-212.[Abstract/Free Full Text]
    30. 30
  30. Hubner, A., X. Yang, D. M. Nolen, T. G. Popova, F. C. Cabello, and M. V. Norgard. 2001. Expression of Borrelia burgdorferi OspC and DbpA is controlled by a RpoN-RpoS regulatory pathway. Proc. Natl. Acad. Sci. USA 98:12724-12729.[Abstract/Free Full Text]
    31. 31
  31. Jonsson, M., L. Noppa, A. G. Barbour, and S. Bergström. 1992. Heterogeneity of outer membrane proteins in Borrelia burgdorferi: comparison of osp operons of three isolates of different geographic origins. Infect. Immun. 60:1845-1853.[Abstract/Free Full Text]
    32. 32
  32. Lahdenne, P., S. F. Porcella, K. E. Hagman, D. R. Akins, T. G. Popova, D. L. Cox, L. I. Katona, J. D. Radolf, and M. V. Norgard. 1997. Molecular characterization of a 6.6-kilodalton Borrelia burgdorferi outer membrane-associated lipoprotein (lp6.6) which appears to be downregulated during mammalian infection. Infect. Immun. 65:412-421.[Abstract]
    33. 33
  33. Liang, F. T., M. J. Caimano, J. D. Radolf, and E. Fikrig. 2004. Borrelia burgdorferi outer surface protein (osp) B expression independent of ospA. Microb. Pathog. 37:35-40.[CrossRef][Medline]
    34. 34
  34. Marconi, R. T., M. E. Konkel, and C. F. Garon. 1993. Variability of osp genes and gene products among species of Lyme disease spirochetes. Infect. Immun. 61:2611-2617.[Abstract/Free Full Text]
    35. 35
  35. Margolis, N., and P. A. Rosa. 1993. Regulation of expression of major outer surface proteins in Borrelia burgdorferi. Infect. Immun. 61:2207-2210.[Abstract/Free Full Text]
    36. 36
  36. Margolis, N., and D. S. Samuels. 1995. Proteins binding to the promoter region of the operon encoding the major outer surface proteins OspA and OspB of Borrelia burgdorferi. Mol. Biol. Rep. 21:159-164.[CrossRef][Medline]
    37. 37
  37. Montgomery, R. R., S. E. Malawista, K. J. M. Feen, and L. K. Bockenstedt. 1996. Direct demonstration of antigenic substitution of Borrelia burgdorferi ex vivo: exploration of the paradox of the early immune response to outer surface proteins A and C in Lyme disease. J. Exp. Med. 183:261-269.[Abstract/Free Full Text]
    38. 38
  38. Narasimhan, S., M. J. Camaino, F. T. Liang, F. Santiago, M. Laskowski, M. T. Philipp, A. R. Pachner, J. D. Radolf, and E. Fikrig. 2003. Borrelia burgdorferi transcriptome in the central nervous system of non-human primates. Proc. Natl. Acad. Sci. USA 100:15953-15958.[Abstract/Free Full Text]
    39. 39
  39. Narasimhan, S., F. Santiago, R. A. Koski, B. Brei, J. F. Anderson, D. Fish, and E. Fikrig. 2002. Examination of the Borrelia burgdorferi transcriptome in Ixodes scapularis during feeding. J. Bacteriol. 184:3122-3125.[Abstract/Free Full Text]
    40. 40
  40. Ohnishi, J., J. Piesman, and A. M. Desilva. 2001. Antigenic and genetic heterogeneity of Borrelia burgdorferi populations transmitted by ticks. Proc. Natl. Acad. Sci. USA 98:670-675.[Abstract/Free Full Text]
    41. 41
  41. Ojaimi, C., C. Brooks, S. Casjens, P. Rosa, A. Elias, A. Barbour, A. Jasinskas, J. Benach, L. Katona, J. Radolf, M. Caimano, J. Skare, K. Swingle, D. Akins, and I. Schwartz. 2003. Profiling of temperature-induced changes in Borrelia burgdorferi gene expression by using whole genome arrays. Infect. Immun. 71:1689-1705.[Abstract/Free Full Text]
    42. 42
  42. Pal, U., A. M. de Silva, R. R. Montgomery, D. Fish, J. Anguita, J. F. Anderson, Y. Lobet, and E. Fikrig. 2000. Attachment of Borrelia burgdorferi within Ixodes scapularis mediated by outer surface protein A. J. Clin. Investig. 106:561-569.[Medline]
    43. 43
  43. Pal, U., and E. Fikrig. 2003. Adaptation of Borrelia burgdorferi in the vector and vertebrate host. Microbes Infect. 5:659-666.[CrossRef][Medline]
    44. 44
  44. Pal, U., X. Li, T. Wang, R. R. Montgomery, N. Ramamoorthi, A. M. Desilva, F. Bao, X. Yang, M. Pypaert, D. Pradhan, F. S. Kantor, S. Telford, J. F. Anderson, and E. Fikrig. 2004. TROSPA, an Ixodes scapularis receptor for Borrelia burgdorferi Cell 119:457-468.[CrossRef][Medline]
    45. 45
  45. Pal, U., X. Yang, M. Chen, L. K. Bockenstedt, J. F. Anderson, R. A. Flavell, M. V. Norgard, and E. Fikrig. 2004. OspC facilitates Borrelia burgdorferi invasion of Ixodes scapularis salivary glands. J. Clin. Investig. 113:220-230.[CrossRef][Medline]
    46. 46
  46. Parveen, N., M. Caimano, J. D. Radolf, and J. M. Leong. 2003. Adaptation of the Lyme disease spirochaete to the mammalian host environment results in enhanced glycosaminoglycan and host cell binding. Mol. Microbiol. 47:1433-1444.[CrossRef][Medline]
    47. 47
  47. Piesman, J., N. S. Zeidner, and B. S. Schneider. 2003. Dynamic changes in Borrelia burgdorferi populations in Ixodes scapularis (Acari: Ixodidae) during transmission: studies at the mRNA level. Vector Borne Zoonotic Dis. 3:125-132.[CrossRef][Medline]
    48. 48
  48. Porcella, S. F., T. G. Popova, D. R. Akins, M. Li, J. D. Radolf, and M. V. Norgard. 1996. Borrelia burgdorferi supercoiled plasmids encode multicopy tandem open reading frames and a lipoprotein gene family. J. Bacteriol. 178:3293-3307.[Abstract/Free Full Text]
    49. 49
  49. Purser, J. E., M. B. Lawrenz, M. J. Caimano, J. K. Howell, J. D. Radolf, and S. J. Norris. 2003. A plasmid-encoded nicotinamidase (PncA) is essential for infectivity of Borrelia burgdorferi in a mammalian host. Mol. Microbiol. 48:753-764.[CrossRef][Medline]
    50. 50
  50. Ramamoorthy, R., and M. T. Philipp. 1998. Differential expression of Borrelia burgdorferi proteins during growth in vitro. Infect. Immun. 66:5119-5124.[Abstract/Free Full Text]
    51. 51
  51. Revel, A. T., A. M. Talaat, and M. V. Norgard. 2002. DNA microarray analysis of differential gene expression in Borrelia burgdorferi, the Lyme disease spirochete. Proc. Natl. Acad. Sci. USA 99:1562-1567.[Abstract/Free Full Text]
    52. 52
  52. Roberts, D. M., M. Caimano, J. McDowell, M. Theisen, A. Holm, E. Orff, D. Nelson, S. Wikel, J. Radolf, and R. T. Marconi. 2002. Environmental regulation and differential production of members of the Bdr protein family of Borrelia burgdorferi. Infect. Immun. 70:7033-7041.[Abstract/Free Full Text]
    53. 53
  53. Samuels, D. S. 1995. Electrotransformation of the spirochete Borrelia burgdorferi. Methods Mol. Biol. 47:253-259.[Medline]
    54. 54
  54. Sartakova, M., E. Dobrikova, and F. C. Cabello. 2000. Development of an extrachromosomal cloning vector system for use in Borrelia burgdorferi Proc. Natl. Acad. Sci. USA 97:4850-4855.[Abstract/Free Full Text]
    55. 55
  55. Schwan, T. G., and J. Piesman. 2000. Temporal changes in outer surface proteins A and C of the Lyme disease-associated spirochete, Borrelia burgdorferi, during the chain of infection in ticks and mice. J. Clin. Microbiol. 38:382-388.[Abstract/Free Full Text]
    56. 56
  56. Schwan, T. G., J. Piesman, W. T. Golde, M. C. Dolan, and P. A. Rosa. 1995. Induction of an outer surface protein on Borrelia burgdorferi during tick feeding. Proc. Natl. Acad. Sci. USA 92:2909-2913.[Abstract/Free Full Text]
    57. 57
  57. Sellati, T. J., D. A. Bouis, M. J. Caimano, J. A. Feulner, C. Ayers, E. Lien, and J. D. Radolf. 1999. Activation of human monocytic cells by Borrelia burgdorferi and Treponema pallidum is facilitated by CD14 and correlates with surface exposure of spirochetal lipoproteins. J. Immunol. 163:2049-2056.[Abstract/Free Full Text]
    58. 58
  58. Seshu, J., J. A. Boylan, F. C. Gherardini, and J. T. Skare. 2004. Dissolved oxygen levels alter gene expression and antigen profiles in Borrelia burgdorferi. Infect. Immun. 72:1580-1586.[Abstract/Free Full Text]
    59. 59
  59. Sohaskey, C. D., W. R. Zuckert, and A. G. Barbour. 1999. The extended promoters for two outer membrane lipoprotein genes of Borrelia spp. uniquely include a T-rich region. Mol. Microbiol. 33:41-51.[CrossRef][Medline]
    60. 60
  60. Stevenson, B., T. G. Schwan, and P. A. Rosa. 1995. Temperature-related differential expression of antigens in the Lyme disease spirochete, Borrelia burgdorferi. Infect. Immun. 63:4535-4539.[Abstract]
    61. 61
  61. Tokarz, R., J. M. Anderton, L. I. Katona, and J. L. Benach. 2004. Combined effects of blood and temperature shift on Borrelia burgdorferi gene expression as determined by whole genome DNA array. Infect. Immun. 72:5419-5432.[Abstract/Free Full Text]
    62. 62
  62. Tommasino, M., S. Ricci, and C. L. Galeotti. 1988. Genome organization of the killer plasmid pGK12 from Kluyveromyces lactis. Nucleic Acids Res. 16:5863-5878.[Abstract/Free Full Text]
    63. 63
  63. Wang, X.-G., B. Lin, J. M. Kidder, S. Telford, and L. T. Hu. 2002. Effects of environmental changes on expression of the oligopeptide permease (opp) genes of Borrelia burgdorferi. J. Bacteriol. 184:6198-6206.[Abstract/Free Full Text]
    64. 64
  64. Yang, X., M. S. Goldberg, T. G. Popova, G. B. Schoeler, S. K. Wikel, K. E. Hagman, and M. V. Norgard. 2000. Interdependence of environmental factors influencing reciprocal patterns of gene expression in virulent Borrelia burgdorferi. Mol. Microbiol. 37:1470-1479.[CrossRef][Medline]
    65. 65
  65. Yang, X., T. G. Popova, M. S. Goldberg, and M. V. Norgard. 2001. Influence of cultivation media on genetic regulatory patterns in Borrelia burgdorferi. Infect. Immun. 69:4159-4163.[Abstract/Free Full Text]
    66. 66
  66. Yang, X., T. G. Popova, K. E. Hagman, S. K. Wikel, G. B. Schoeler, M. J. Caimano, J. D. Radolf, and M. V. Norgard. 1999. Identification, characterization, and expression of three new members of the Borrelia burgdorferi Mlp (2.9) lipoprotein gene family. Infect. Immun. 67:6008-6018.[Abstract/Free Full Text]
    67. 67
  67. Yang, X. F., S. M. Alani, and M. V. Norgard. 2003. The response regulator Rrp2 is essential for the expression of major membrane lipoproteins in Borrelia burgdorferi. Proc. Natl. Acad. Sci. USA 100:1100-1106.
    68. 68
  68. Yang, X. F., A. Hübner, T. G. Popova, K. E. Hagman, and M. V. Norgard. 2003. Regulation of expression of the paralogous Mlp family in Borrelia burgdorferi. Infect. Immun. 71:5012-5020.[Abstract/Free Full Text]
    69. 69
  69. Yang, X. F., U. Pal, S. M. Alani, E. Fikrig, and M. V. Norgard. 2004. Essential role for OspA/B in the life cycle of the Lyme disease spirochete. J. Exp. Med. 199:641-648.[Abstract/Free Full Text]

Journal of Bacteriology, November 2005, p. 7845-7852, Vol. 187, No. 22
0021-9193/05/$08.00+0     doi:10.1128/JB.187.22.7845-7852.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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