IN BRIEF

What Do Space Rocks Have to Do With Preterm Birth?

November 9, 2016
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A brief history of nanobacteria and their implications for human health.

I remember when nanobacteria were a really big deal. Press-conference-by-POTUS-about-evidence-of-extraterrestrial-life-level big deal.

I hadn’t thought much about them until recently, when they made a surprise appearance in a presentation on idiopathic preterm birth by Irina Buhimschi, MD, director of the Center for Perinatal Research at The Research Institute at Nationwide Children’s Hospital and The Ohio State University. But I’ll come back to that.

In 1996, David McKay, a scientist at NASA, published a study identifying the possible fossils of “nanobacteria” he found in a meteorite originating from Mars and found in Antarctica. While nanobacteria were first described by geologist Robert Folk in 1993, his initial discovery flew under the radar until it became implicated in evidence of extraterrestrial life.

These discoveries ignited a debate that continued long after the headlines ran their course. Just what were these structures? Were they really alive?

Not everyone thought so. Nanobacteria were initially described as 10 to 500 nanometers (nm) in diameter. The smallest nanobacteria were smaller than a ribosome (20 nm diameter), so how could they contain even perfunctory machinery needed to function as a living cell?

Then, in 1998, researchers in Finland described pathogenic nanobacteria that were able to kill mammalian cells in culture and were present in human blood and kidney stones.

The Finnish discovery proved to be a catalyst for the work uncovering the molecular mechanisms of formation of the particles and the scientific community’s new name for these fascinating particles.

These particles – once called nanobacteria, then propagating calcifying nanoparticles, now calciprotein particles – are replicating particles made up of hydroxyapatite and proteins. The chemistry involved is fascinating. For the sake of relevance, I’ll stick to the chemistry of how they form in the body. It’s been a while since Organic Chemistry class, for some of us, so let’s keep this simple:

Blood, serum and other body fluids are supersaturated with calcium. They are also rich in phosphorous, oxygen and hydrogen. When these four elements get together, they tend to form hydroxyapatite. Some proteins – notably fetuin and albumin – are attracted to hydroxyapatite. In fact, fetuin is a systemic inhibitor of spontaneous biomineralization in the body. By attaching to newly formed hydroxyapatite, fetuin helps to maintain the correct distribution of hydroxyapatite in the body: inside bones and away from arteries and other soft tissues. As fetuin is consumed, the protein-mineral complexes coalesce and precipitate, forming round, amorphous nanoparticles – calciprotein particles.

This is an over simplified version of the story, and we know that other organic molecules are often involved. As organic and mineral layers coalesce, bits of these other available organic molecules – RNA, DNA, lipids and carbohydrates – are incorporated.

When scientists grow calciprotein particles in culture, the crystallization continues after the proteins are used up, ultimately resulting in an amorphous sheet.

Jan Martel and colleagues propose a continuum of morphology dependent upon time and availability of organics and ions in their paper published in Nanomedicine in 2014. Their continuum would explain the presence and variety of morphologies described throughout the sordid history of calciprotein particle research – from small amorphous nanoparticles to biofilms.

So now that we’ve established what these particles are, the next big question remains: How are they implicated in a plethora of human disease?

As the research community’s understanding of calciprotein particles has grown, it is clearer that they may be etiological agents of conditions previously thought to be idiopathic. Since 1993, researchers have reported the association of “mineral nanoparticles” in pathological calcification processes, such as atherosclerosis, Alzheimer’s disease, osteoarthritis, calcific aortic valve disease and kidney stones.

Now comes the latest chapter. Dr. Buhimschi of Nationwide Children’s has demonstrated for the first time the association of calciprotein particles in amniotic fluid with preterm birth. In a newly published work in Science Translational Medicine, Dr. Buhimschi and her colleagues at Yale and The Ohio State University found that in perterm premature rupture of the fetal membranes – that is, water breaking significantly early – the amniotic sac contains calcium deposits and early markers of bone formation. The membranes then are less elastic and more prone to breaking. They also showed how the deposits occur and that amniotic fluid can also produce calciprotein particles. You can read the full release here.

Once thought to be from outer space, we are continuing to realize just now connected these particles are to human life.

References:

  1. Young JD, Martel J. The rise and fall of nanobacteria. Scientific American. Jan 2010;302:52-59.
  2. Martel J, Peng H-H, Young D, Wu C-Y, Young JD. Of nanobacteria, nanoparticles, biofilms and their role in health and disease: Facts, fancy and future. Nanomedicine. 2014;9(4):483-499.
  3. Shook L, Buhimschi C, Dulay A, McCarthy M, Hardy J, Buniak C, Zhao G, Buhimschi I. Calciprotein particles as potential etiologic agents of idiopathic preterm birth. Science Translational Medicine.  2016 Nov 9 [Epub ahead of print]