Generation of Mammalian Host-Adapted Borrelia burgdorferi by Cultivation in Peritoneal Dialysis Membrane Chamber Implantation in Rats
The transmission, survival, and virulence of Borrelia burgdorferi depend upon the spirochete’s ability to modulate its transcriptome as it cycles between its arthropod vector and reservoir host. This complex adaptive process is collectively referred to as “host-adaptation.” The paucibacillary nature of borrelial infections precludes the detailed analysis of host adaptation within infected mammalian tissues. To circumvent this limitation, we (J Clin Invest 101:2240–2250, 1998) developed a model system whereby spirochetes are cultivated within dialysis membrane chambers (DMCs) surgically implanted within the peritoneal cavity of a rat. Spirochetes within DMCs are exposed to many, if not all, of the environmental signals and physiological cues required for mammalian host adaptation but are protected from clearance by the host’s immune system.
Key wordsBorrelia burgdorferi Lyme disease Spirochetes Host adaptation Gene expression Animal models
The authors would like to thank Ms. Anna Allard for her superb technical assistance and Dr. Justin Radolf for his continued support of this work. This work is supported by NIH Grants AI029735 and AI 126146 and an American Heart Association Grant-in-Aid award.
Generation of mammalian host-adapted Borrelia burgdorferi by cultivation in peritoneal dialysis membrane chamber implantation in rats. Subheading 3.2, Preparation of DMCs (MP4 25016 kb)
Generation of mammalian host-adapted Borrelia burgdorferi by cultivation in peritoneal dialysis membrane chamber implantation in rats. Subheading 3.3, Peritoneal implant procedure (MP4 313609 kb)
- 7.Pal U, Fikrig E (2010) Tick interactions. In: Samuels DS, Radolf JD (eds) Borrelia molecular biology, host intercations and pathogenesis. Caister Academic Press, Norfolk, UK, pp 279–298Google Scholar
- 8.Skare JT, Carroll JA, Yang XF, Samuels DS, Akins DR (2010) Gene regulation, transcriptomics, and proteomics. In: Samuels DS, Radolf JD (eds) Borrelia molecular biology, host interactions and pathogenesis. Calister Academic Press, Norfolk, UKGoogle Scholar
- 12.Ojaimi C, Brooks C, Casjens S, Rosa P, Elias A, Barbour A, Jasinskas A, Benach J, Katona L, Radolf J, Caimano M, Skare J, Swingle K, Akins D, Schwartz I (2003) Profiling of temperature-induced changes in Borrelia burgdorferi gene expression by using whole genome arrays. Infect Immun 71:1689–1705CrossRefPubMedPubMedCentralGoogle Scholar
- 16.Caimano MJ, Iyer R, Eggers CH, Gonzalez C, Morton EA, Gilbert MA, Schwartz I, Radolf JD (2007) Analysis of the RpoS regulon in Borrelia burgdorferi in response to mammalian host signals provides insight into RpoS function during the enzootic cycle. Mol Microbiol 65:1193–1217CrossRefPubMedPubMedCentralGoogle Scholar
- 20.Elias AF, Stewart PE, Grimm D, Caimano MJ, Eggers CH, Tilly K, Bono JL, Akins DR, Radolf JD, Schwan TG, Rosa P (2002) Clonal polymorphism of Borrelia burgdorferi strain B31 MI: implications for mutagenesis in an infectious strain background. Infect Immun 70:2139–2150CrossRefPubMedPubMedCentralGoogle Scholar
- 22.Caimano MJ, Sivasankaran SK, Allard A, Hurley D, Hokamp K, Grassmann AA, Hinton JC, Nally JE (2014) A model system for studying the transcriptomic and physiological changes associated with mammalian host-adaptation by Leptospira interrogans serovar Copenhageni. PLoS Pathog 10:e1004004CrossRefPubMedPubMedCentralGoogle Scholar