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nanobacteria
National Academy of Sciences

Nanobacteria: not a life-form?


November 27, 2000: Nanobacteria are putative cell-walled microorganisms with a diameter well below the generally accepted lower limit (about 0.2 micrometers) for bacteria. In July, 1998, Finnish scientists, Olavi Kajander and Neva Ciftcioglu, attracted widespread attention with a paper in the Proceedings of the U.S. National Academy of Science (PNAS, 1) reporting the apparent culture of nanobacteria and the partial characterization of a nanobacterial ribosomal RNA.

In that paper, Kajander and Ciftcioglu report the isolation of nanobacteria from human blood, cow blood and commercial blood serum preparations, and describe the formation by nanobacteria of microscopic mineral structures composed of apatite, a calcium- and phosphate-containing mineral found in teeth and bone. They advanced this process of "biomineralization" as a possible cause of pathological calcification in humans such as the formation of kidney stones.

The Finnish scientists produced nanobacteria and their associated mineral structures in a medium containing 10% blood serum, which served as the presumed source of the nanobacterial inoculum. Control cultures prepared with gamma-irradiated serum were free of nanobacteria. Apatite formations generated during culture resembled flattened hollow spheres with an opening facing the bottom of the culture dish, which, the authors stated, are "apparently the dwelling place of the organisms."

Now, John Cisar and colleagues at NIH and FDA labs in Bethesda, Maryland have reported the results of their attempt to reproduce the findings of Kajander and Ciftcioglu (2). They were able to confirm the appearance of nanobacteria-like formations under the culture conditions described by Kajander and Ciftcioglu. Otherwise, however, their findings were mostly unsupportive of the Finnish work.

The Finnish scientists reported a ribosomal RNA derived from their cultures that they identified, on the basis of its nucleotide sequence, as originating from a novel nanobacterial species. However, Cisar et al. demonstrate that this RNA sequence is virtually identical to that of ribosomal RNA from Phyllobacterium mysinacearum, a common contaminant of the reagents used in nucleotide sequence analysis. This is a particularly forceful criticism because the sequence analysis studies of Kajander and Ciftcioglu did not include reagent controls.

In support of their contention that nanobacteria possess a similar metabolism to normal bacteria, Kajander and Ciftcioglu reported that multiplication of nanobacteria is sensitive to tetracycline and citrate. However, Cisar et al. point out that these compounds can inhibit calcification, and that other antibiotics did not inhibit nanobacterial replication, nor did heat treatment or treatment with sodium azide, a powerful respiratory inhibitor. Furthermore, they argue that gamma radiation, which prevents nanobacterial multiplication, could inactivate nonliving yet organic precursors of mineralization, e.g., phospholipid complexes.

Perhaps most damaging to the nanobacterial hypothesis is the observation by Cisar et al. that the spherical particles previously identified as nanobacterial cells, as well as the "dwelling" structures, resemble inanimate structures that form spontaneously in sterile solutions of inorganic calcium and phosphate salts combined with organic material, as found in the medium used to culture nanobacteria.

However, not all of the Finnish observations are disposed of by the most recent study, including the report that nanobacterial "infection" of mammalian 3T6 cells results in the appearance of nanobacteria, or at least calcium-rich deposits, in multiple vacuoles within the cells. Cisar et al. did not attempt to reproduce or explain this observation, but one possible interpretation is suggested by the origin of the 3T6 cell line. These cells are derived from fibroblasts, which control limb and blood vessel development in mammals. Several congenital bone malformation diseases are directly traceable to mutations in fibroblast cell lines. Perhaps, therefore, fibroblasts are conditioned to control the deposition of apatite in the body, which may include the internalization of excess minerals formed in the blood or organs. Indeed, apatite crystals have been shown to cause inflammation when injected into joints. Many malignant diseases involve calcification of tissues, but it is not clear whether it is necessary to postulate the existence of an infectious agent as a cause; rather these conditions may stem from defects in one of several calcification-preventing blood serum proteins, or an inability of fibroblasts to properly control mineralization.

At present, the molecular basis for biomineralization, and the possible role, if any, that nanobacteria play in this process remains unclear. Future research in this area is likely, therefore, to prove of value in elucidating the etiology of diseases involving pathological mineralization, whether this process is mediated by a novel life form, the host itself, or solely by physical processes.

References

1. Kajander, E.O. and N. Ciftcioglu. 1998. Nanobacteria: an alternative mechanism for pathogenic intra- and extracellular calcification and stone formation. Proc. Nat. Acad. Sci. 95:8274-8279. Full text of the article

2. Cisar, J.O., D.-Q. Xu, J. Thompson, W. Swaim, L. Hu and D.J. Kopecko. 2000. An alternative interpretation of nanobacteria-induced biomineralization. Proc. Nat. Acad. Sci. 97:11,511-11,515. Full text of the article

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