This is the sixth of 6 guest posts on infection and chronic disease.
By Courtney Cook
Kidney stone disease affects approximately 5% of Americans. While several risk factors are well-established, including genetic predisposition, metabolic diseases, lifestyle, and diet, there are still questions over the actual mechanism of calcium stone formation. Many cases do not have any kind of underlying disorder and therefore it is difficult to know how to treat these patients to prevent further stone formation.
This seemed to change when, in 1998, Kajandar and Ciftcioglu isolated an unusual microorganism in human kidney stones. Less than 100 nm across, the authors termed them “nanobacteria.” They claimed to observe self-replication as well as to have identified a unique DNA sequence. This seemed to indicate a living entity that may be playing a role in stone formation. Are they?
(More after the jump…)
Nanobacteria have been found within mineralized “igloos” of apatite, a calcium-rich mineral. These structures were thought to possibly play a role in calcification in the kidney, as well as other structures within the body. Nanobacteria have been reported to be present in several pathological calcifications, including atherosclerosis, osteoarthritis, prostate stones, periodontal disease, as well as bodies in ovarian and mammary cancers. The actual mechanism of apatite formation by nanobacteria is unknown
Kajandar and Ciftcioglu have since taken the lead on nanobacteria research. They have further characterized nanobacteria as Gram-negative, ranging in size from 80-500 nm, and observable through transmission electron microscopy. They have also claimed to observe nanobacteria forming small colonies surrounded by their thick apatite coat under low nutrient and other extreme conditions. For example, a study based on increase in kidney stone formation in astronauts during and after long duration zero-gravity missions looked at growth of nanobacteria in microgravity, where it was determined that nanobacteria in simulated microgravity conditions had a significantly higher multiplication rate when compared to those in stationary or shaken culture conditions.
Specifically regarding kidney stone disease, results from several studies (most of which include Kajandar and/or Ciftcioglu as authors) suggest that nanobacteria may be associated with stone formation. An apparent dose-response relationship was observed when inoculating rats with nanobacteria – but that study was done with a sample size of four, bringing into question the power of such an experiment and whether any observations made would truly be significant.
Naturally, there is a great deal of controversy surrounding these ideas. Many question whether nanobacteria are even living in the first place. A study by Cisar et al directly brought Kajandar and Ciftcioglu’s original results into question, suggesting that the DNA they found was actually a contaminant from a regular bacterium and there were no unique nucleic acids within the sequence. We would expect to see a unique DNA sequence if it was the DNA of nanobacteria being detected.
Contradictions also seem to arise when looking at methods used to detect the nanobacteria. Kajandar and Ciftcioglu use their own patented methods for culture of nanobacteria, but “traditional” microbiological method have failed to detect or culture nanobacteria. They have since turned these methods into financial gain, with the establishment of Nanobac Life Sciences, a company that develops and sells diagnostic kits for finding nanobacteria, as well as treatments for conditions that nanobacteria supposedly cause. This lucrative arrangement brings into question the true motives of the pair.
Right now it is really too soon to tell whether nanobacteria are causative agents for kidney stones and other conditions. Before identifying them as a cause, we first need to settle the debate surrounding their existence. With the lack of substantial evidence from multiple sources in either direction, more research is needed to try to determine the truth behind these mysterious entities.
Courtney Cook is a first year M.S. student in epidemiology, and currently holds a B.A. in mathematics. Her research interests involve infectious disease epidemiology, particularly in children. She hopes to apply these interests toward her ultimate career goal of practicing medicine, specializing in pediatrics.
References
Ciftcioglu N, Bjorklund M, Kuorikoski K, Bergstrom K, Kajandar EO. (1999). Nanobacteria: an infectious cause for kidney stone formation. Kidney International 56: 1893-1898. Link.
Ciftcioglu N, Haddad RS, Golden DC, Morrison DR, McKay DS. (2005). A potential cause for kidney stone formation during space flights: enhanced growth of nanobacteria in microgravity. Kidney International 67: 483-491. Link.
Hogan, J. (2004). Nanobacteria revelations provoke new controversy. New Scientist. Link.
Kajandar EO, Ciftcioglu N, Miller-Hjelle MA, Hjielle JT. (2001). Nanobacteria: controversial pathogens in nephrolithiasis and polycystic kidney disease. Current Opinion in Nephrology and Hypertension 10: 445-452. Link.
Kajandar EO, Ciftcioglu N, Aho K, Garcia-Cuerpo E. (2003). Characteristics of nanobacteria and their possible role in stone formation. Urol Res 31: 47-54. Link.
Urbano P, Urbano F. (2007). Nanobacteria: facts or fancies?. PLoS Pathog 3(5): 567-570. Link.