Identification and Functional Characterization of the
            <i>Neisseria gonorrhoeae lbpB</i>
            Gene Product

Biswas, G D; Anderson, John M.; Chen, Ching Ju; Cornelissen, Cynthia Nau; Sparling, P. Frederick

doi:10.1128/iai.67.1.455-459.1999

Cited by 48 publications

(40 citation statements)

References 30 publications

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“…To scavenge all traces of free iron for this assay, 2.5 M apo-lactoferrin was added to each culture after the initial 2-h growth period and dilution. Because strain FA1090 and its derivatives are unable to utilize lactoferrin as an iron source due to a natural deletion in the lactoferrin receptor (4,24), no iron was available for growth. If a utilizable iron source is then added to this medium, the bacteria regain the ability to grow.…”

Section: Methodsmentioning

confidence: 99%

Ferric Enterobactin Binding and Utilization by Neisseria gonorrhoeae

et al. 1999

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FetA, formerly designated FrpB, an iron-regulated, 76-kDa neisserial outer membrane protein, shows sequence homology to the TonB-dependent family of receptors that transport iron into gram-negative bacteria. Although FetA is commonly expressed by most neisserial strains and is a potential vaccine candidate for bothNeisseria gonorrhoeae and Neisseria meningitidis, its function in cell physiology was previously undefined. We now report that FetA functions as an enterobactin receptor. N. gonorrhoeae FA1090 utilized ferric enterobactin as the sole iron source when supplied with ferric enterobactin at approximately 10 μM, but growth stimulation was abolished when an omega (Ω) cassette was inserted withinfetA or when tonB was insertionally interrupted. FA1090 FetA specifically bound59Fe-enterobactin, with a Kd of approximately 5 μM. Monoclonal antibodies raised against theEscherichia coli enterobactin receptor, FepA, recognized FetA in Western blots, and amino acid sequence comparisons revealed that residues previously implicated in ferric enterobactin binding by FepA were partially conserved in FetA. An open reading frame downstream of fetA, designated fetB, predicted a protein with sequence similarity to the family of periplasmic binding proteins necessary for transporting siderophores through the periplasmic space of gram-negative bacteria. An Ω insertion withinfetB abolished ferric enterobactin utilization without causing a loss of ferric enterobactin binding. These data show that FetA is a functional homolog of FepA that binds ferric enterobactin and may be part of a system responsible for transporting the siderophore into the cell.

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Section: Methodsmentioning

confidence: 99%

Ferric Enterobactin Binding and Utilization by Neisseria gonorrhoeae

et al. 1999

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“…All strains of N. meningitidis have the capacity to utilize haemoglobin, lactoferrin and transferrin (Marri et al, 2010). In contrast, approximately half of gonococcal isolates have undergone a large deletion in Iron import in pathogenic Neisseria 247 the locus encoding the lactoferrin-iron internalization system, rendering this system inactive (Biswas et al, 1999). Further, engineered gonococcal mutants unable to utilize lactoferrin and transferrin as iron sources were found to be avirulent in a human male infection model of gonococcal disease (Cornelissen et al, 1998), attesting to the importance of these iron transport systems in initiating infection and proliferating in humans.…”

Section: Iron Import Systems In Pathogenic Neisseriamentioning

confidence: 99%

The transferrin–iron import system from pathogenic Neisseria species

Noinaj

Buchanan

Cornelissen

2012

Molecular Microbiology

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Summary The two pathogenic species within the genus Neisseria cause the diseases gonorrhea and meningitis. While vaccines are available to protect against four N. meningitidis serogroups, there is currently no commercial vaccine to protect against serogroup B or against N. gonorrhoeae. Moreover, the available vaccines have significant limitations and with antibiotic resistance becoming an alarming issue, the search for effective vaccine targets to elicit long-lasting protection against Neisseria species is becoming more urgent. One strategy for vaccine development has targeted the neisserial iron import systems. Without iron, the Neisseriae cannot survive and therefore these iron import systems tend to be relatively well conserved and are promising vaccine targets, having the potential to offer broad protection against both gonococcal and meningococcal infections. These efforts have been boosted by recent reports of the crystal structures of the neisserial receptor proteins TbpA and TbpB, each solved in complex with human transferrin, an iron binding protein normally responsible for delivering iron to human cells. Here, we review the recent structural reports and put them into perspective with available functional studies in order to derive the mechanism(s) for how the pathogenic Neisseriae are able to hijack human iron transport systems for their own survival and pathogenesis.

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“…The loss of Lf binding by NM and NG lbpA mutants, as assayed by solid-phase dot blot assays, indicated that LbpB alone did not mediate Lf binding (55,139). Liquid phase equilibrium binding assays confirmed the conclusion that LbpA is required for Lf binding (202). What, then, is the role of the LbpB lipoprotein?…”

Section: Lbpab (Lactoferrin Receptor)mentioning

confidence: 82%

“…What, then, is the role of the LbpB lipoprotein? Mutants lacking this receptor component exhibit reduced growth with Lf, a ~50% reduction in Lf binding capacity, and 55 Fe uptake rates 60% of wild-type LbpAB (55,202,203). These results suggest an important, but non-essential, role for LbpB in the binding and internalization of Lf-Fe.…”

Section: Lbpab (Lactoferrin Receptor)mentioning

confidence: 91%

“…These results suggest an important, but non-essential, role for LbpB in the binding and internalization of Lf-Fe. Several lines of evidence support the conclusion that LbpB can bind Lf independently of LbpA (199,200,202,203). It is unclear why assays of lbpA mutant strains expressing only LbpB failed to detect binding to Lf.…”

Section: Lbpab (Lactoferrin Receptor)mentioning

confidence: 99%

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Mechanisms of iron acquisition by the human pathogens Neisseria Meningitidis and Neisseria Gonorrhoeae

Rohde¹

2003

Front Biosci

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It is well established that bacterial pathogenesis is dependent on the ability to acquire iron within the host. The success of the highly adapted obligate human pathogens Neisseria meningitidis (NM) and Neisseria gonorrhoeae (NG) can be attributed in part to the efficient utilization of multiple host iron (Fe) sources, allowing replication on mucosal surfaces, in the bloodstream, and intracellularly. Most Gram-negative bacterial strategies for scavenging iron from the human host rely on the TonB protein to energize active iron transport across the outer membrane. Pathogenic Neisseria express multiple high-affinity iron transporters including a family of two-component TonB-dependent receptors as well as multiple single-component TonB-dependent Fe transporters. This review describes our current understanding of the mechanisms Neisseria have evolved to utilize various iron sources encountered during infection of the human host. Recent studies have provided insight into the interaction of neisserial outer membrane receptors with host iron carrier proteins. Emerging structural information on neisserial iron transporters will be compared with the crystal structures and biochemical data available for homologous Escherichia coli TonB-dependent Fe-siderophore receptors. In the process, we will highlight the aspects of the iron transport process that are unique and those that remain to be experimentally demonstrated in Neisseria. These include receptor structure/function, the mechanism of iron removal from protein ligands, the fate of Fe and heme-Fe after traversing the outer membrane, and the role of TonB-associated energy in receptor functions. Finally, we will discuss regulatory mechanisms that control the expression of iron scavenging systems. The investigation of iron metabolism in NM and NG is important for understanding the biochemistry of this virulence factor, the development of vaccines targeted at outer membrane iron receptors, and therapeutic interventions exploiting these transporters as high affinity drug delivery systems.

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Identification and Functional Characterization of the Neisseria gonorrhoeae lbpB Gene Product

Cited by 48 publications

References 30 publications

Ferric Enterobactin Binding and Utilization by Neisseria gonorrhoeae

Ferric Enterobactin Binding and Utilization by Neisseria gonorrhoeae

The transferrin–iron import system from pathogenic Neisseria species

Mechanisms of iron acquisition by the human pathogens Neisseria Meningitidis and Neisseria Gonorrhoeae

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