The Tp38 (TpMglB-2) Lipoprotein Binds Glucose in a Manner Consistent with Receptor Function in
            <i>Treponema pallidum</i>

Deka, Ranjit K.; Goldberg, Martin; Hagman, Kayla E.; Norgard, Michael V.

doi:10.1128/jb.186.8.2303-2308.2004

Cited by 17 publications

(25 citation statements)

References 43 publications

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“…In classical gramnegative organisms, the ABC transporter MglABC has specificity for galactose (126,212). The homologous Mgl system in T. pallidum (21,236,299) may also bind galactose, but it has been speculated that, because of its inability to utilize galactose as a carbon source, T. pallidum may utilize MglABC as a glucose transporter (81). Ribose may be taken into the cell via an ABC transporter with homology to the RbsAC transporter system in the related spirochete Borrelia burgdorferi; however, carbon utilization studies demonstrated that ribose is not degraded by T. pallidum (217).…”

Section: Limited Metabolic Capacitymentioning

confidence: 99%

Biological Basis for Syphilis

2006

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SUMMARY Syphilis is a chronic sexually transmitted disease caused by Treponema pallidum subsp. pallidum. Clinical manifestations separate the disease into stages; late stages of disease are now uncommon compared to the preantibiotic era. T. pallidum has an unusually small genome and lacks genes that encode many metabolic functions and classical virulence factors. The organism is extremely sensitive to environmental conditions and has not been continuously cultivated in vitro. Nonetheless, T. pallidum is highly infectious and survives for decades in the untreated host. Early syphilis lesions result from the host's immune response to the treponemes. Bacterial clearance and resolution of early lesions results from a delayed hypersensitivity response, although some organisms escape to cause persistent infection. One factor contributing to T. pallidum's chronicity is the paucity of integral outer membrane proteins, rendering intact organisms virtually invisible to the immune system. Antigenic variation of TprK, a putative surface-exposed protein, is likely to contribute to immune evasion. T. pallidum remains exquisitely sensitive to penicillin, but macrolide resistance has recently been identified in a number of geographic regions. The development of a syphilis vaccine, thus far elusive, would have a significant positive impact on global health.

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Section: Limited Metabolic Capacitymentioning

confidence: 99%

Biological Basis for Syphilis

2006

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“…In fact, genome analysis predicts that T. pallidum devotes as much as 3% of its genetic coding capacity to lipoproteins (15). However, to date, with one exception (9,16), comparative sequence analyses have not been fruitful for predicting the functions of treponemal lipoproteins, and the inability to cultivate (and thus genetically manipulate) the organism has precluded using classical gene inactivation approaches (17) for investigating the functions of treponemal membrane lipoproteins.…”

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confidence: 99%

The PnrA (Tp0319; TmpC) Lipoprotein Represents a New Family of Bacterial Purine Nucleoside Receptor Encoded within an ATP-binding Cassette (ABC)-like Operon in Treponema pallidum

Deka

Brautigam

Yang

et al. 2006

Journal of Biological Chemistry

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Treponema pallidum, the bacterial agent of syphilis, cannot be cultivated in vitro. This constraint has severely impeded the study of the membrane biology of this complex human pathogen. A structure-to-function approach thus was adopted as a means of discerning the likely function of Tp0319, a 35-kDa cytoplasmic membraneassociated lipoprotein of T. pallidum formerly designated as TmpC. A 1.7-Å crystal structure showed that recombinant Tp0319 (rTp0319) consists of two ␣/␤ domains, linked by three crossovers, with a deep cleft between them akin to ATP-binding cassette (ABC) receptors. In the cleft, a molecule of inosine was bound. Isothermal titration calorimetry demonstrated that rTp0319 specifically binds purine nucleosides (dissociation constant (K d ) ϳ10 ؊7 M). This predilection for purine nucleosides by rTp0319 is consistent with its likely role as a receptor component of a cytoplasmic membraneassociated transporter system. Reverse transcription-PCR analysis of RNA isolated from rabbit tissue-extracted T. pallidum additionally showed that tp0319 is transcriptionally linked to four other downstream open reading frames, thereby supporting the existence of an ABC-like operon (tp0319 -0323). We herein thus re-name tp0319 as purine nucleoside receptor A (pnrA), with its operonic partners tp0320 -0323 designated as pnrB-E, respectively. Our study not only infers that PnrA transports purine nucleosides essential for the survival of T. pallidum within its obligate human host, but to our knowledge, this is the first description of an ABC-type nucleoside transport system in any bacterium. PnrA has been grouped with a functionally uncharacterized protein family (HBG016869), thereby implying that other members of the family may have similar nucleoside-binding function(s).Treponema pallidum, the bacterial agent of syphilis, cannot be cultivated continuously in vitro (1). Historically, this constraint has severely hampered progress in understanding many features of this enigmatic pathogen. More specifically, key aspects of the membrane biology of T. pallidum, particularly as it pertains to the interaction of the pathogen with its human host, remain poorly defined (2-4). The initial discovery of membrane lipoproteins in T. pallidum (5, 6) spawned new avenues of investigation into treponemal membrane biology, inasmuch as in other bacteria, lipoproteins have importance as virulence factors, modular components of ATP-binding cassette (ABC) 3 transporters, receptors, protective immune targets, and proinflammatory agonists that elicit innate immune responses (7-14). In fact, genome analysis predicts that T. pallidum devotes as much as 3% of its genetic coding capacity to lipoproteins (15). However, to date, with one exception (9, 16), comparative sequence analyses have not been fruitful for predicting the functions of treponemal lipoproteins, and the inability to cultivate (and thus genetically manipulate) the organism has precluded using classical gene inactivation approaches (17) for investigating the functions of treponemal ...

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“…The mechanism(s) by which the parasite acquires and utilizes these essential nutrients can potentially help explain the peculiar membrane biology of T. pallidum, elucidate key aspects of its parasitic strategy, and prompt new avenues of investigation for potentially novel antimicrobial drug targets. To this end, we have found that many of the likely transport systems of T. pallidum are predicated on the organism's membrane lipoproteins (5)(6)(7)(8)(9)(10)(11)(12)(13), and, as a result, the organism devotes a large percentage of its genome to encoding these lipoproteins (3,14,15). Unfortunately, many of the putative lipoproteins are hypothetical (i.e.…”

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confidence: 99%

The TP0796 Lipoprotein of Treponema pallidum Is a Bimetal-dependent FAD Pyrophosphatase with a Potential Role in Flavin Homeostasis

Deka

Brautigam

Liu

et al. 2013

Journal of Biological Chemistry

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Background:The TP0796 lipoprotein of Treponema pallidum belongs to the poorly characterized ApbE superfamily. Results: TP0796 hydrolyzed FAD into FMN and AMP, consistent with the general enzymatic mechanism of an FAD pyrophosphatase. Conclusion: This novel metal-dependent enzyme probably plays an essential role in flavin homeostasis in T. pallidum. Significance: This is the first description of a metal-dependent FAD pyrophosphatase in bacteria.

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The Tp38 (TpMglB-2) Lipoprotein Binds Glucose in a Manner Consistent with Receptor Function in Treponema pallidum

Cited by 17 publications

References 43 publications

Biological Basis for Syphilis

Biological Basis for Syphilis

The PnrA (Tp0319; TmpC) Lipoprotein Represents a New Family of Bacterial Purine Nucleoside Receptor Encoded within an ATP-binding Cassette (ABC)-like Operon in Treponema pallidum

The TP0796 Lipoprotein of Treponema pallidum Is a Bimetal-dependent FAD Pyrophosphatase with a Potential Role in Flavin Homeostasis

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