Novel nickel transport mechanism across the bacterial outer membrane energized by the TonB/ExbB/ExbD machinery.
Nickel is a cofactor for various microbial enzymes, yet as a trace element, its scavenging is challenging. In the case of the pathogen Helicobacter pylori, nickel is essential for the survival in the human stomach, because it is the cofactor of the important virulence factor urease. While nickel transport across the cytoplasmic membrane is accomplished by the nickel permease NixA, the mechanism by which nickel traverses the outer membrane (OM) of this Gram-negative bacterium is unknown. Import of iron-siderophores and cobalamin through the bacterial OM is carried out by specific receptors energized by the TonB/ExbB/ExbD machinery. In this study, we show for the first time that H. pylori utilizes TonB/ExbB/ExbD for nickel uptake in addition to iron acquisition. We have identified the nickel-regulated protein FrpB4, homologous to TonB-dependent proteins, as an OM receptor involved in nickel uptake. We demonstrate that ExbB/ExbD/TonB and FrpB4 deficient bacteria are unable to efficiently scavenge nickel at low pH. This condition mimics those encountered by H. pylori during stomach colonization, under which nickel supply and full urease activity are essential to combat acidity. We anticipate that this nickel scavenging system is not restricted to H. pylori, but will be represented more largely among Gram-negative bacteria.
Schauer
Kristine
K
Unité de Pathogénie Bactérienne des Muqueuses, Département de Microbiologie, Institut Pasteur, 75724 Paris Cedex 15, France.
Gouget
Barbara
B
Carrière
Marie
M
Labigne
Agnès
A
de Reuse
Hilde
H
D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D016480:Helicobacter pylori / Q000235:genetics / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D009532:Nickel / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014510:Urease / Q000378:metabolism
D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D008565:Membrane Proteins; C057616:tonB protein, Bacteria; D009532:Nickel; D007501:Iron; D014510:Urease