Lack of a Role for Iron in the Lyme Disease Pathogen

Posey, James E.; Gherardini, Frank C.

doi:10.1126/science.288.5471.1651

Cited by 459 publications

(397 citation statements)

References 19 publications

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“…Some enzymes shown to be crucial for bacterial survival in a mammalian host (although dispensable for growth in rich culture medium) include PncA, a nicotinamidase involved in production of NAD [109], and two products involved in purine nucleotide synthesis [32,110]. Another unusual feature of B. burgdorferi is that it does not contain intracellular iron and, hence, does not use iron as a co-factor for enzymes [111], thereby facilitating survival in the iron-poor mammalian environment.…”

Section: B Burgdorferi Products Required For Mammalian Infectionmentioning

confidence: 99%

Biology of Infection with Borrelia burgdorferi

Tilly

Rosa

Stewart

2008

Infectious Disease Clinics of North America

183

177

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The spirochete Borrelia burgdorferi is a tick-borne obligate parasite whose normal reservoir is a variety of small mammals [1]. Whereas infection of these natural hosts does not lead to disease, infection of humans can result in Lyme disease, as a consequence of the human immunopathological response to B. burgdorferi [2,3]. Consistent with the pathogenesis of Lyme disease, bacterial products that allow B. burgdorferi to replicate and survive, rather than true "virulence factors," appear to be primarily what is required for the bacterium to cause disease in a susceptible host. In support of this idea, the genome sequence of B31, the type strain of B. burgdorferi sensu stricto [4,5], revealed that the bacterium lacks factors common to many bacterial pathogens, such as lipopolysaccharide, toxins, and specialized secretion systems. In this chapter, we will describe the basic biology of B. burgdorferi, and some of the bacterial components required to infect and survive in the mammalian and tick hosts.

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Section: B Burgdorferi Products Required For Mammalian Infectionmentioning

confidence: 99%

Biology of Infection with Borrelia burgdorferi

Tilly

Rosa

Stewart

2008

Infectious Disease Clinics of North America

183

177

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“…Initial Fe-reconstitution studies assayed the possible utilization of Fe via Fe-loaded transferrin (Tf). To further define metal composition, Sh-2-82 was grown in BSK-Excyte (BSK-E) medium (Posey and Gherardini, 2000) with modifications of metal content. The formulation of BSK-E medium is compared with that of BSK-II medium in Table 1.…”

Section: Methodsmentioning

confidence: 99%

“…Only three metalloproteins have been identified in borreliae; these include a SOD, a ferric-uptake regulator protein (Fur), and a putative neutrophil-activating protein Fraser et al, 1997). Posey and Gherardini (2000) Iron concentration in another spirochete, Treponema denticola, was measured also and found to be slightly reduced (3.5 nmol) in comparison to E. coli (4.2 nmol). Relatively few Febinding proteins have been predicted from the genome of Treponema pallidum (Fraser et al, 1998).…”

Section: F Metalloregulation Of Oxidative Stressmentioning

confidence: 99%

“…Fe requirements contrary to that of eubacteria (Posey et al, 1999;Jovanovic et al, 2000;Posey and Gherardini, 2000). Iron has been considered a growth-limiting factor for microorganisms in most natural environments due to its participation in diverse biological processes, such as cellular respiration and transcriptional regulation (Briat, 1992).…”

Section: F Metalloregulation Of Oxidative Stressmentioning

confidence: 99%

“…burgdorferi (Posey and Gherardini, 2000). It was reported that culturing B. burgdorferi in BSK-E resulted in growth rates and motility similar to those of cells grown in BSK-II medium (Posey and Gherardini, 2000).…”

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Characterization of secA-sod operon in Borrellia burgdorferi.

Nichols¹

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Borrelia burgdorferi, the causative agent of Lyme disease, has been characterized as a microaerophilic spirochete. O2 consumption and utilization potentially yield reactive oxygen intermediates, such as superoxide, hydroxyl radicals, and hydrogen peroxide. This study investigated the expression of the sod gene, which encodes the only, identified oxidative defense mechanism in B. burgdorferi. Using primer extension analysis and RT-PCR, it was found that sod and secA are organized as a single transcriptional unit under the control of σ 70 -like promoter upstream of the secA open reading frame. Generally, gene expression decreases with increased distance from the promoter; however, secA expression was observed to be relatively lower amounts than sod. Both genes were expressed in all phases of growth, with greatest expression observed in stationary phase. Because transcription of most sod genes is tightly regulated by iron concentration, the secA-sod gene expression was analyzed in borrelial cells grown in varying amounts of metal. Ironrestriction did not significantly affect growth nor did it affect transcription of secA or sod.Likewise, no major differences in transcription were observed with restricting or supplementing media with manganese. To test the possibility that the borrelial SOD may function with either iron or manganese as a cofactor as in cambialistic SODs, SOD activity was assayed and the highest activity was observed in increased manganese concentrations.Protein expression profiles of Sh-2-82 cultured in metal-defined media were investigated by one-and two-dimensional gel electrophoresis. Approximately 15 proteins were differentially expressed in response to metal concentration. iv ACKNOWLEDGMENTS

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Iron Transport: Siderophores

Matzanke

2005

Encyclopedia of Inorganic Chemistry

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Siderophores (from the Greek: iron carrier) are low molecular mass (500–1500 Da) iron chelators that are synthesized in bacteria and fungi under conditions of iron deficiency. Siderophores exhibit extraordinarily high complex formation constants for ferric iron with β‐values ranging from 10 20 to approximately 10 50 . Fe 2+ ‐siderophores are some 20 orders of magnitude less stable than their Fe 3+ counterparts. The d5 electronic configuration of Fe 3+ rules out any crystal field stabilization energy and makes ferric iron complexes relatively labile with respect to isomerization and ligand exchange. Siderophores display a selectivity for iron that is reflected in the corresponding complex stability constants that are higher with Fe 3+ than with Al 3+ , or with bivalent cations like Ca 2+ , Cu 2+ or Zn 2+ . Microorganisms excrete desferrisiderophores in order to scavenge iron from the environment. The competition for iron by siderophores, the mechanisms of siderophore uptake through microbial membranes, and the intracellular pathways of siderophore‐iron utilization strongly depend on thermodynamic, kinetic, and structural features of the ferric iron siderophore complexes. The structural features of siderophores are diverse. The ligating groups contain oxygen atoms of hydroxamate, catecholate, α‐hydroxy carboxylic and salicylic acids, or oxazoline and thiazoline nitrogen. Reduction potentials of ferric siderophore complexes vary between −700 and −150 mV. In particular at the low potential end below −450 mV, special biological strategies of reductive iron removal are required because these potentials are too negative for typical cellular reductases. The coordination and redox chemistry of siderophores is also reflected in the mechanisms of siderophore‐mediated iron uptake in microorganisms. A classic example is the intracellular removal of iron from enterobactin. The permeation of cell walls or bacterial membranes by siderophores is in most microbes a highly specific process requiring an array of up to eight proteins. The advent of modern molecular biology delivered a cornucopia of methods enabling high‐yield production of specific gene products relevant to siderophore synthesis and transport, analyses of structure‐function relationships (employing site directed mutagenesis), and detailed insights into the regulation of the corresponding processes. One siderophore, ferrioxamine B, serves as a detoxifier in iron overload diseases and in the treatment of β‐thalassemia. Siderophores and siderophore analogs also play a role in MRI and are employed as basic models for actinide chelators in order to remove these metals from the environment or from a contaminated body.

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Lack of a Role for Iron in the Lyme Disease Pathogen

Cited by 459 publications

References 19 publications

Biology of Infection with Borrelia burgdorferi

Biology of Infection with Borrelia burgdorferi

Characterization of secA-sod operon in Borrellia burgdorferi.

Iron Transport: Siderophores

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