How Lyme Disease Bacteria ‘Hide’ from the Immune System – The Biochemistry of Lyme Disease

lyme disease morphology spirochaete familyThe biochemistry of Lyme disease bacteria involves their nutritional needs, both for growth and for optimum activity, and the outer surface proteins which are key in their interaction with cellular components in their hosts.  The nutrient requirements for Borrelia appear considerably more involved than for other similar spirochaetes such as Leptospira. Borrelia require glucose, amino acids, N-acetyl-glucosamine, several vitamins, and long-chain fatty acids to survive and thrive and may double their generation time in an artificial medium in comparison to growth in a mammalian host.

Lyme Disease Bacteria – Biochemical Conversations

Outer surface proteins have received considerable attention by those studying Borrelia bacteria and Lyme disease as these are the lipoproteins which communicate with the cells in the host environment. The variation and apparent flexibility of the expression of these Osps has serious ramifications for the detection of infection, treatment of infection, and the hosts’ own immune system response to Borelia bacteria.  The most heavily researched of the Osps is OspA which is expressed on those spirochaetes found in adult ticks and unfed nymphs.  OspA is also found on spirochaetes grown in culture and was the target of the Lyme disease vaccine which was briefly introduced in the 1990s.  OspA regulates the adherence of the bacteria to cells in the ticks’ midgut which is likely to be important in preventing the spirochaetes from being killed during the ticks’ digestion process.  Upon a second round of feeding the Borrelia bacteria then alter their OspA expression to allow them to detach from the ticks’ midgut and migrate to the host mammal as the tick feeds.


During this feeding process the spirochaetes also increase the expression of OspC and the bacteria move towards the ticks’ salivary glands.  Certain substances in the saliva of the Ixodes ticks are though to be used by Borrelia to aid transmission into the hosts’ body.  OspA expression is decreased after the spirochaete enters the mammalian host whereas OspC expression is more complex, showing variable rates of upregulation.  Different strains of Borrelia show slightly altered sequences of the OspC gene which can complicate detection by the immune system and affect diagnosis of Lyme disease.

The Cystic Form of Borrelia Burgdorferi

Doctors and patients have been asserting for years that the bacteria which cause Lyme disease, Borrelia burgdorferi sensu lato, have the ability to ‘hide’ from the immune system and from antibiotics, thereby evading eradication and remaining latent in a sufferer with the ability to create clinical relapse.  This has been largely disputed by medical authorities but some evidence is emerging that a cystic form of Borrelia can occur which can later generate the spirochaete form given the right environmental conditions.  In becoming this cystic, or coccoid, form the bacteria may persist in a host in a similar way to the bacteria which causes syphilis, Treponema pallidum.  The long, latent stage observed in syphilis followed by chronic central nervous system infection and inflammation is attributed to this ability by the bacteria to morph into atypicla cystic and granular forms prior to generating spirochaetes at a later date.

Inducing the Cystic Form of Lyme Disease


Miklossy (et al, 2008) investigated the induction of atypical forms of Borrelia burgdorferi (strains B31 and ADB1) following exposure to a variety of unfavorable conditions in the laboratory.  Such environmental distrubances include osmotic and heat shock and exposure to binding agents Thioflavin S and Congo red.  The study also looked at the induction of these forms of Borrelia in vitro using models of infection of chicken and rat neurons, and rat and human astrocytes. Patients with Lyme neuroborreliosis were also examined for evidence of these atypical Borrelia forms using immunohistochemical methods.  The researchers found atypical cystic, rolled and granular forms of the spirochaetes with three patients with neuroborreliosis showing evidence of the atypical and cystic forms similar to those induced in the laboratory.  

The use of dark field and atomic force microscopy is not widespread in diagnosis of Lyme disease but such studies may lead to its adoption as part of complicated chronic cases of suspected Lyme neuroborreliosis.  The local neuroinflammation in these patients may be explained by the persistence of these more resistant spirochaetes in the neurons and glial cells and contribute to cellular dysfunction and apoptosis.  Where a negative test result for spiral form Borrelia occurs it may be beneficial to use alternate testing methods to check for these atypical cystic forms of Borrelia only just being understood as part of Lyme disease morphology.

References

Miklossy,J., Kasas, S., Zurn, A.D., McCall, S., Yu, S., McGeer, P.L., (2008). Persisting atypical and cystic forms of Borrelia burgdorferiand local inflammation in Lyme neuroborreliosis. J Neuroinflammation, 5: 40.