Health authorities continue to deny the existence of chronic infection and research out this week finds that recurrence of Lyme disease symptoms is most commonly due to reinfection rather than relapse. However, Dr Eva Sapi and colleagues in Connecticut have published a paper detailing the process by which Borrelia form biofilms, potentially offering an explanation for persistent symptoms and a new target for testing and drug development.
How Borrelia Biofilms Form
Biofilms are adherent polysaccharide-based matrices that allow bacteria to colonise in hostile environments. They usually form on surfaces regularly in contact with water and colonies generally contain bacteria, yeasts, fungi and/or protozoa that themselves produce a mucilaginous protective coating (a polysaccharide-based matrix). This formation can protect individual bacterial cells as aggregates on biotic and abiotic surfaces. Biofilm formation by other chronically infectious organisms has been found to be dependent on the regulation of the molecule cyclic di-GMP with attempts made to map the process in order to find a way to disrupt it. Recent research into Lyme disease has uncovered evidence that B. burgdorferi also expresses this regulatory molecule, giving credence to the concept of biofilm formation in Lyme disease.
How Lyme Disease Bacteria Hide from the Immune System
Borrelia burgdorferi appears to continually rearrange its structure, allowing it to remain in mobile spirochaetal form when environmental conditions are right and cystic forms when the host environment becomes hostile. The research published last month comes courtesy of Dr. Eva Sapi, UNH associate professor of biology and environmental science, and elucidates how Borrelia burgdorferi can create biofilms that resist all forms of antibiotics currently available. Understanding whether other strains of Borrelia are capable of biofilm formation could go some way towards explaining why disease symptoms persist even after treatment the CDC and IDSA consider effective.
Biofilms and Antibiotic Resistance
There are currently no effective treatments to eradicate biofilms which are responsible for a variety of chronic infections such as periodontitis, chronic otitis media, endocarditis, chronic lung infection and gastrointestinal infection. Lyme disease may now be added to that list, courtesy of the work by Sapi and MacDonald. These researchers raised the idea of biofilm formation by Borrelia burgdorferi in 2008/2009 and more recent research has found spirochaetal colonies in the tick gut and in culture.
Chronic Lyme Disease ‘Proof’?
The controversial topic of Chronic Lyme Disease often touches upon the idea of resistant pockets of infection made up of borrelial cysts and biofilms, with some evidence of this in samples taken from patients and studied under the microscope. A more comprehensive understanding of biofilms may allow researchers to design new antibiotics that disrupt the steps leading towards biofilm formation. Mutations in genes regulating biofilm development do appear to compromise new biofilms and lead to the destruction of existing bacterial colonies, suggesting a target for drug development to treat Lyme disease biofilms.
Improving Lyme Disease Tests and Treatment
Growing recognition of the existence of cell-wall deficient (CWD) forms and biofilms in persistent Borrelia burgdorferi infection will likely prompt pharmaceutical research into antimicrobial agents capable of eradicating these types of infection. In addition, knowing more about the forms which bacteria take, such as Lyme disease biofilms, should help initiate proteomic screening and address problems with current Lyme disease tests.
Sapi E, Bastian SL, Mpoy CM, Scott S, Rattelle A, et al. (2012) Characterization of Biofilm Formation by Borrelia burgdorferi In Vitro. PLoS ONE 7(10): e48277. doi:10.1371/journal.pone.0048277
Sapi E, MacDonald A. Biofilms of Borrelia burgdorferi in chronic cutaneous borreliosis. Am J Clin Pathol. 2008;129:988–989.
100. Dunham-Ems SM, Caimano MJ, Pal U, et al. Live imaging reveals a biphasic mode of dissemination of Borrelia burgdorferi within ticks. J Clin Invest. 2009;119:3652–3665.
Rogers EA, Terekhova D, Zhang HM, Hovis KM, Schwartz I, Marconi RT. Rrp1, a cyclic-di-GMP-producing response regulator, is an important regulator of Borrelia burgdorferi core cellular functions. Mol Microbiol. 2009;71:1551–1573.
Freedman JC, Rogers EA, Kostick JL, et al. Identification and molecular characterization of a cyclic-di-GMP effector protein, PlzA (BB0733): additional evidence for the existence of a functional cyclic-di-GMP regulatory network in the Lyme disease spirochete, Borrelia burgdorferi. FEMS Immunol Med Microbiol. 2010;58:285–294.