Metamorphosis of Borrelia burgdorferi organisms – RNA, lipid and protein composition in context with the spirochetes' shape

Abstract

Borrelia burgdorferi, the agent of Lyme borreliosis, has the ability to undergo morphological transformation from a motile spirochetal to non-motile spherical shape when it encounters unfavorable conditions. However, little information is available on the mechanism that enables the bacterium to change its shape and whether major components of the cells--nucleic acids, proteins, lipids--are possibly modified during the process. Deducing from investigations utilizing electron microscopy, it seems that shape alteration begins with membrane budding followed by folding of the protoplasmatic cylinder inside the outer surface membrane. Scanning electron microscopy confirmed that a deficiency in producing functioning periplasmic flagella did not hinder sphere formation. Further, it was shown that the spirochetes' and spheres' lipid compositions were indistinguishable. Neither phosphatidylcholine nor phosphatidylglycerol were altered by the structural transformation. In addition, no changes in differential protein expression were detected during this process. However, minimal degradation of RNA and a reduced antigen-antibody binding activity were observed with advanced age of the spheres. The results of our comparisons and the failure to generate mutants lacking the ability to convert to spheres suggest that the metamorphosis of B. burgdorferi results in a conditional reconstruction of the outer membrane. The spheres, which appear to be more resistant to unfavorable conditions and exhibit reduced immune reactivity when compared to spirochetes, might allow the B. burgdorferi to escape complete clearance and possibly ensure long-term survival in the host.

Evaluation of in-vitro antibiotic susceptibility of different morphological forms of Borrelia burgdorferi

“…The change in phenotypic expression could also lead to structural alterations in the spirochete form and induction of the cyst form, a knob-shaped structure containing one or multiple spirochetes 21–24. Cysts have a low metabolic rate that enables them to survive in a hostile environment until conditions become favorable for them to multiply again 21–25.…”

“…Both cysts and granules are together referred to as round body forms in this study. Several studies have shown that B. burgdorferi can convert from the spirochete form to the round body form in vitro when presented with an unfavorable environment, and the organism can revert back to the spirochete form when conditions are again favorable for growth 21–24. The presence of atypical forms of B. burgdorferi may be the reason why the spirochete can survive in infected tissues for years or even for decades 21–24…”

Lyme Disease Frontiers: Reconciling Borrelia Biology and Clinical Conundrums

“…As seen in Figure 4, the most commonly published method of inducing round RB forms of Borrelia spp. is through osmotic shock via exposure to distilled water [313,314,321,[327][328][329]. Water shock is also consistently reported to be the fastest for the conversion of large proportions of spirochetes into round bodies (Table A1).…”

“…are not only inducible in vitro, but they have also been detected within the enzootic life cycle of the spirochete, specifically within the midgut of the tick vector [336]. These forms have been loosely described as spherules, granules, gemmae, cysts, coccoid forms, and round bodies at different points throughout the literature (Table 4; [270,313,314,328,329,333,334,337]). Likewise, a wide variety of methods have been used to generate and evaluate these forms, and yet the resulting morphotypes are treated synonymously (Table A1).…”

Chronic Lyme Disease: An Evidence-Based Definition by the ILADS Working Group

“…Immune evasion via alterations in its physical structure may also contribute to Bbsl survival. Such alterations include phasic and antigenic variations [149][150][151][152][153], producing changes in the expression of outer surface proteins (Osp), and morphologic changes leading to cell-wall deficient forms, round bodies, spherocytes and "cyst" forms [154][155][156][157][158][159].…”