Generalized Niches: A Tentative Definition

As long as Bb or toxin populations exist in niches, they can reinfect/reinvade the host, trigger the immune response and thus produce symptoms (e.g. H. Smith: Spirochetal antigen persistence: chronic Lyme).

Niches are provided by the host in the form of physical compartments (immune privileged sites), but they can also be produced by Bb itself in the form of immunomodulation or chemical or microbiological defense mechanisms.
(see also:
Hiding from the Immune System, in: Tobias A Rupprecht, Uwe Koedel, Volker Fingerle and Hans-Walter Pfister "The Pathogenesis of Lyme Neuroborreliosis: From Infection to Inflammation", Mol Med. 2008 Mar-Apr; 14(3-4): 205-212, and
the overview in Chapter Background Information of J.J. Burrascano's essay "Managing Lyme Disease")

1. physical compartments:
   Host provided niches are sites poorly accessible to antibiotics and normal immune surveillance.
   Examples
   • Sherr VT, "Bell's Palsy of the Gut" and Other GI Manifestations of Lyme and Associated Diseases, Practical Gastroenterology, April 2006
   • Fallon BA, Nields JA, Microbiology of Borrelia burgdorferi, in: "Lyme Disease: A Neuropsychiatric Illness", an overview, The American Journal of Psychiatry 1994;151,11:1571-1583.
   • intracellular locations in which Bb were found
   • mechanisms of cell invasion,
   • Mecaila E. McClune et al., The peptidoglycan of Borrelia burgdorferi can persist in discrete tissues and cause systemic responses consistent with chronic illness, Science Translational Medicine 23 April 2025.

2. modulation of the host's immune and hormone system:
   Examples
   • Isabel Diterich, Immunomodulation and new therapeutic strategies in Lyme borreliosis, Dissertation (Dr. rer. nat.), Universität Konstanz, 2003.(in Cache)
   • Diterich I, Härter L, Hassler D, Wendel A and Hartung T, Modulation of Cytokine Release in Ex Vivo-Stimulated Blood from Borreliosis Patients (in cache)

3. chemical or microbiological defense mechanisms:
   Bb might provide its own chemical and microbiological niches
• by shedding glycoprotein that forms strong complexes with antibodies (Schutzer et al., 1994), thereby enabling the organism itself to escape immune surveillance (Lawrence et al., 1995),
• by producing beta-lactamases, reducing the permeablity of the outer cell membrane or modifying the target of the antibiotic, the "penicillin binding proteins", so that the attachment of the antibiotic is reduced (Chambers et al., 1998), 
• by changing its outer surface (Zhang et al., 1997), e.g. developing cell wall deficient (CWD) forms (Preac-Mursic et al. 1996). Mattman 1993 interprets the ubiquitous CWD forms of bacteria and fungi as states of a variable equilibrium between cell wall (ZW) and outer membrane (AM) dissolving and rebuilding processes, the former being driven by lysozymes of the organism itself and external stressors, e.g. antibiotics. According to Phillips et al. 1998 immune system and antibiotics shift this equilibrium in blood of Lyme patients to CWD forms. Together with the blood the CWD forms of Bb may spread throughout the host. Because the penetration of both the immune system and antibiotic into an organ (or compartment) varies from organ to organ, so will the equilibrium form of Bb. In some locations even the parent (spirochetal) form may be able to exist. Thus, the blood compartment may be thought of as a niche releasing Bb into other host compartments.
• by producing biofilms or settling in biofilms already present.

The basic concept underlying the model is that the niche has the following properties:

• The immune system or antibiotic needs long periods, possibly several months, to empty a niche.
• Since the toxins (antigen, pathogen) within a niche are only "poorly visible" to the immune system, they do not stimulate an inflammatory immune response while in the niche.
• Depending on the concentration in the niche (and other parameters), a niche releases its content into the compartments under immune system or antibiotic surveillance, the "visible" compartments responsible for the symptoms.

More Literature

• Stricker RB, Counterpoint: Long-Term Antibiotic Therapy Improves Persistent Symptoms Associated with Lyme Disease, Clin Infect Dis. (2007) 45 (2): 149-157
  • Pathophysiology of Lyme Disease,
  • Immunosuppression
  • Stealth Pathology of Borrelia burgdorferi (in cache)

• Bergström S, Reactivation and immune evasion of Borrelia infection, Project description, Umea, Sweden, April 2005

• Liang FT, Brown EL, Wang T, Iozzo RV and Fikrig E, Protective Niche for Borrelia burgdorferi to Evade Humoral Immunity. American Journal of Pathology. 2004;165:977-985>
• Zajkowska J, Hermanowska-Szpakowicz T, Rubel J. [Atypical forms of Borrelia burgdorferi-clinical consequences], Pol Merkuriusz Lek. 2005 Jan;18(103):115-9. Polish.

  defense mechanisms include

  1. plasmid encoded genes,
  2. morphologic variants,
  3. cysts formation,
  4. colonies formation,
  5. antigenic variation, and
  6. resistance to iron deprivation