MAY 31, 2016 07:48 AM PDT

Metals Present Potential New Target In the Fight Against Bacteria

WRITTEN BY: Carmen Leitch
Trace metals are a critical part of survival for every cell; metals give structural support to proteins, catalyze reactions, facilitate electron transfer, and work as signals. Scavenging is a vital skill in environments where metal is low in abundance, like inside of a host organism. This is especially important for pathogenic bacteria that have developed complex systems to compensate for the low concentration of essential metals in their typical living conditions. A balance between having too much or too little must be delicately maintained.

That balance is very important to the pathogenicity of an infection. It’s been shown that the acquisition of metals confers virulence in animal models of bacterial infection. Mammalian hosts will start withholding metals in response to microbial infection in an effort to starve the microbe.
Metal capture
Scientists in Sweden at the Laboratory for Molecular Infection Medicine Sweden (MIMS) at Umeå University and colleagues have reported the discovery of a unique acquisition method for essential metals in Staphylococcus aureus, a pathogenic bacterium. S.aureus uses a metal scavenging molecule, newly called staphylopine, to bind and mediate the transport of iron, copper, nickel, cobalt, and zinc ions.
Staphylopine is a small molecule that gets exported from the cell and captures transition metals in the extracellular space. The metals get then taken back into the cell by a special channel, where they then provide the nutrients needed for pathogenicity. Based on all of the evidence, it would seem that Staphylopine is quite a versatile metal carrier (a metallophore) that contributes significantly to staphylococcal virulence.
An SEM image (false-colred) shows the S.aureus (0.5 to 1.0 µm in diameter) on finger ridges.
Staphylopine production is not only observed in S. aureus either. Pseudomonas aeruginosa and Yersinia pestis are just a couple of the other pathogenic bacteria in which genes like those encoding for staphylopine are found.
"Remarkably, a few years ago we found that many, taxonomically unrelated, bacteria can release high concentrations of a wide variety of D-amino acids to the environment. Therefore, D-histidine might be just one D-amino acid of many that could serve as a building block for novel staphylopine-like molecules," said Felipe Cava, of MIMS/Umeå University.
Characterizing staphylopine; figuring out how it is assembled, as well as how gets transported may now pave the way for the creation of a new strategy to fight pathogenic bacteria - targeting their need for metals.
Interestingly, staphylopine resembles nicotianamine closely. Nicotianamine is a molecule found in all plants that ensures the delivery of essential metals from where they are collected in the roots to the aerial organs. The discovery of a comparable metal scavenger in three kingdoms of life (eukaryotes, archaea and now bacteria) would indicate there may be an ancient origin for this kind of molecule.
Sources: Science - G.Ghssein et al, AAAS, Science - E. Nolan
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