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Rare minerals and the fight against pathogenic bacteria

July 10, 2010

I’ve kinda been on a microbe love-fest recently, but don’t get me wrong – there are some seriously nasty bugs out there. We have antibiotics, which are great, but a lot of pathogens are developing resistance, and antibiotics can do all kinds of crazy stuff that we don’t understand to the natural commensals in our gut and elsewhere. Vaccines would be great, but it’s really hard to make vaccines against bacteria.

Most vaccines against viruses work through neutralizing antibodies, which can bind to incoming viruses and prevent them from fusing with cells. But compared to viruses, bacteria are huge, and anyway they don’t infect cells in the same way (if they even infect cells at all). Some bacteria make toxins that can be neutralized (that’s how the tetanus vaccine works), but toxins are usually small molecules, so neutralizing antibodies can be effective. So what other options do we have?

An new paper in PLoS Pathogens has an idea:

In a search for putative vaccine components, we have characterized here a new receptor of Neisseria meningitidis, a resident of the nasopharynx that occasionally causes sepsis and meningitis. We show that expression of this receptor is induced under zinc limitation and that the protein is involved in the uptake of zinc[…] the protein appears an excellent candidate for the development of a vaccine against N. meningitidis, for which no universal vaccine is available yet.

Bacteria can generally make all the biological components they need to survive from relatively simple precursors. But they also need a few trace metals as co-factors, and these metals in very short supply. To get what they need, bacteria have special pumps in their outer membrane to pull those metals in, and these authors reasoned that blocking these pumps with antibodies might work as a vaccine target. It looks like they were right.

Building on work done on an iron pump, these guys found a pump that is necessary for zinc uptake in the bacterium Neisseria meningitidis. Crucially, this protein is highly conserved, meaning it’s almost identical across many different strains (making a vaccine is way less useful if it only targets a small subset of the bacteria you’re after). Then they tested to see whether they could immunize mice with this protein and generate an antibody response that was bacteriocidal.

Unfortunately, they didn’t show any data to say that these immunized mice were actually protected against subsequent infection (they just took antibodies from their blood and showed that they could kill the bugs ex vivo), but this is a good first step, and a potentially cool new way to make vaccines against some of the more dangerous bacteria that infect us.

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