Nickel and Virulence in Bacterial Pathogens

Abstract

While the importance of iron during bacterial virulence is largely documented, much less is known on nickel, which is nevertheless an essential element for several bacteria. This chapter will present the few cases in which the link between nickel and bacterial virulence has been formally demonstrated. [NiFe] hydrogenase, principally, provides some pathogens an energy source in gastrointestinal niches. Urease is directly involved in pathogenicity mainly in microorganisms infecting urine and in Helicobacter pylori colonizing the stomach. Over a few years, H. pylori has become a paradigm of the relation between nickel and virulence. The mechanisms of nickel transport, trafficking, and regulation in H. pylori are presented as well as its unusual nickel binding proteins. The three nickel transporters important for the uropathogenesis of Staphylococcus aureus are described together with the recent discovery of a metallophore/nickelophore synthesis pathway involved in nickel uptake by an ABC transporter. Several reports suggest that additional virulence-related functions of nickel enzymes and novel transport mechanisms are expected to be discovered in the coming years.

Role of Nickel in Microbial Pathogenesis

“…Nickel release from Hpn and Hpnl is observed under acidic conditions, suggesting that these proteins may supply nickel when urease is also needed (e.g., to combat acidity, see [207]). Expression of the storage proteins confers nickel resistance to E. coli, confirming their ability to sequester excess nickel [201]. Based on studies with pure proteins or on H. pylori mutant strain in-lab phenotypes, the initial suggestions that these proteins might play nickel storage roles in vivo was supported by use of mice maintained under strict nickel-limited conditions [208] or NMRI-specific pathogen-free mice [202].…”

“…These small His-rich proteins, named Hpn and Hpn-like (referred to herein as Hpnl), contain 47% and 25% His, respectively. Interestingly, both are confined to the gastric colonizing types of Helicobacters [201]. However, Hpn is present in every gastric Helicobacter species, and Hpnl is restricted to H. pylori and its closely related species H. acinonychis, originally isolated from cheetah [202].…”

Bioinorganic Chemistry of Nickel

“…The current global regulatory focus is toward ecosystem-level protection, with environmental guidelines and standards being based on chronic, rather than acute toxicity endpoints. To this end, chronic laboratory ecotoxicity data based on ecologically relevant endpoints (e.g., growth, reproduction, mortality) are the focus, where "chronic" refers to adverse effects caused by exposure to nickel for a substantial (>10%) portion of the lifespan of the test organism, or effects experienced during the most sensitive life stage [201].…”

“…Nickel release from Hpn and Hpnl is observed under acidic conditions, suggesting that these proteins may supply nickel when urease is also needed (e.g., to combat acidity, see [207]). Expression of the storage proteins confers nickel resistance to E. coli, confirming their ability to sequester excess nickel [201]. Based on studies with pure proteins or on H. pylori mutant strain in-lab phenotypes, the initial suggestions that these proteins might play nickel storage roles in vivo was supported by use of mice maintained under strict nickel-limited conditions [208] or NMRI-specific pathogen-free mice [202].…”