HOST ADAPTED BORRELIA

Topics with information and discussion about published studies related to Lyme disease and other tick-borne diseases.
Joe Ham
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HOST ADAPTED BORRELIA

Post by Joe Ham » Tue 25 Sep 2007 3:42

Published 11 February 2002. doi:10.1084/jem.20011870
© Rockefeller University Press, 0022-1007/2002/2/415/ $5.00
The Journal of Experimental Medicine, Volume 195, Number 4, February 18, 2002 415-422

An Immune Evasion Mechanism for Spirochetal Persistence in Lyme Borreliosis

Fang Ting Liang , Mary B. Jacobs , Lisa C. Bowers and Mario T. Philipp

Department of Parasitology, Tulane Regional Primate Research Center, Tulane University Health Sciences Center, Covington, LA 70433

Address correspondence to Mario T. Philipp, Tulane Regional Primate Research Center, Tulane University Health Sciences Center, 18703 Three Rivers Rd., Covington, LA 70433. Phone: 985-871-6221; Fax: 985-871-6390; E-mail: philipp@tpc.tulane.edu

Borrelia burgdorferi, the Lyme disease spirochete, persistently infects mammalian hosts despite the development of strong humoral responses directed against the pathogen.

Here we describe a novel mechanism of immune evasion by B. burgdorferi.

In immunocompetent mice, spirochetes that did not express ospC (the outer-surface protein C gene) were selected within 17 d after inoculation, concomitantly with the emergence of anti-OspC antibody.

Spirochetes with no detectable OspC transcript that were isolated from immunocompetent mice reexpressed ospC after they were either cultured in vitro or transplanted to naive immunocompetent mice, but not in OspC-immunized mice. B. burgdorferi persistently expressed ospC in severe combined immune-deficient (SCID) mice. Passive immunization of B. burgdorferi–infected SCID mice with an anti-OspC monoclonal antibody selectively eliminated ospC-expressing spirochetes but did not clear the infection.

OspC-expressing spirochetes reappeared in SCID mice after the anti-OspC antibody was eliminated.

We submit that selection of surface-antigen nonexpressers is an immune evasion mechanism that contributes to spirochetal persistence.

http://www.jem.org/cgi/content/abstract/195/4/415

*****************************************************

Genetics, Vol. 168, 713-722, October 2004, Copyright © 2004
doi:10.1534/genetics.104.028738

ospC Diversity in Borrelia burgdorferi
Different Hosts Are Different Niches


Dustin Brisson1 and Daniel E. Dykhuizen

Department of Ecology and Evolution, Stony Brook University, Stony Brook, New York 11794-5245

1 Corresponding author: Department of Ecology and Evolution, Stony Brook University, Stony Brook, NY 11794-5245.

E-mail: brisson@life.bio.sunysb.edu

The outer surface protein C (ospC) locus of the Lyme disease bacterium, Borrelia burgdorferi, is at least an order of magnitude more variable than other genes in the species.

This variation is classified into 22 ospC major groups, 15 of which are found in the northeastern United States. The frequency distributions of ospC within populations suggest that this locus is under balancing selection. In multiple-niche polymorphism, a type of balancing selection, diversity within a population can be maintained when the environment is heterogeneous and no one genotype has the highest fitness in all environments. Genetically different individuals within vertebrate species and different vertebrate species constitute diverse environments for B. burgdorferi.

We examined four important host species of B. burgdorferi and found that the strains that infected each species had different sets of ospC major groups.

We found no variation among conspecific hosts in the ospC major groups of their infecting strains. These results suggest multiple niches create balancing selection at the ospC locus.

http://www.genetics.org/cgi/content/abstract/168/2/713

Joe Ham
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Re: HOST ADAPTED BORRELIA

Post by Joe Ham » Sat 29 Sep 2007 3:43

Infect Immun. 1999 Jan;67(1):36-42.

Specificity of infection-induced immunity among Borrelia burgdorferi sensu lato species.
Barthold SW.

Center for Comparative Medicine, School of Medicine, University of California, Davis 95616, USA. swbarthold@ucdavis.edu

The specificity of infection-induced immunity in mice infected with cultured or host-adapted Borrelia burgdorferi sensu lato, the agent of Lyme disease, was examined.
Sera obtained from mice following infection with high and low doses of cultured B. burgdorferi sensu stricto, transplantation of infected tissue (host-adapted spirochetes), or tick-borne inoculation all showed protective activity in passive immunization assays.
Infection and disease were similar in mice infected with cultured spirochetes or by transplantation. Thus, the adaptive form of inoculated spirochetes did not influence the immune response during active infection.

Mice infected with B. burgdorferi sensu stricto and then cured of infection with an antibiotic during early or late stages of infection were resistant to challenge with high doses of homologous cultured spirochetes for up to 1 year.

In contrast, actively immune mice infected with different Borrelia species (B. burgdorferi sensu lato, B. burgdorferi sensu stricto cN40, Borrelia afzelii PKo, and Borrelia garinii PBi) and then treated with an antibiotic were resistant to challenge with cultured homologous but not heterologous spirochetes.

Similar results were achieved for actively immune mice challenged by transplantation and by passive immunization with sera from mice infected with each of the Borrelia species and then challenged with cultured spirochetes.

Arthritis and carditis in mice that had immunizing infections with B. afzelii and B. garinii and then challenged by transplantation with B. burgdorferi sensu stricto were equivalent in prevalence and severity to those in nonimmune recipient mice.

These results indicate that protective immunity and disease-modulating immunity that develop during active infection are universal among species related to B. burgdorferi sensu lato but are species specific.

PMID: 9864193 [PubMed - indexed for MEDLINE]

Joe Ham
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Re: HOST ADAPTED BORRELIA

Post by Joe Ham » Sat 29 Sep 2007 3:49

J Infect Dis. 1998 Feb;177(2):395-400.
Immune evasion by tickborne and host-adapted Borrelia burgdorferi.
de Silva AM, Fikrig E, Hodzic E, Kantor FS, Telford SR 3rd, Barthold SW.

Center for Comparative Medicine, School of Medicine, University of California, Davis 95616, USA.

Immune sera from mice infected with the Lyme disease spirochete, Borrelia burgdorferi, have strong biologic activity against spirochetes cultured in vitro.

Recent studies with rodents and ticks infected with B. burgdorferi indicate that spirochetes undergo major changes in protein expression as they adapt to the diverse environments encountered by a vectorborne pathogen.

The purpose of this study was to explore the susceptibility of three different adaptive forms of B. burgdorferi (in vitro cultured, host-derived, and tickborne) to immune sera.

Passive transfer of immune sera protected mice when they were challenged with spirochetes cultured in vitro.
Immune sera did not protect mice from tickborne spirochetes or spirochetes derived from infected mice.

These results indicate that spirochetes that have adapted within either the feeding tick or host are relatively invulnerable to the protective effects of immune sera, unlike spirochetes grown in vitro, which are highly susceptible.

PMID: 9466527 [PubMed - indexed for MEDLINE]

Does this explain the reason for the failure of Lymerix?

Martian
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Re: HOST ADAPTED BORRELIA

Post by Martian » Sat 29 Sep 2007 3:54

Very interesting information, it show how "clever" the nasty Borrelia is.
May indeed (partly) explain the reason for the failure of Lymerix.

Joe Ham
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Re: HOST ADAPTED BORRELIA

Post by Joe Ham » Sat 29 Sep 2007 5:47

I really don't know where I'm going with this; just posting pieces to this thread as I find them and hoping someone else will be smart enough to put the pieces together.

Joe Ham
Posts: 489
Joined: Fri 27 Jul 2007 6:15
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Re: HOST ADAPTED BORRELIA

Post by Joe Ham » Sat 27 Oct 2007 3:44

Infect Immun. 2003 Jul;71(7):4003-10.
Host-adapted Borrelia burgdorferi in mice expresses OspA during inflammation.
Crowley H, Huber BT.

Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.

Antibody responses to outer surface protein A (OspA) [30-31 kDa] of Borrelia burgdorferi may occur during periods of arthritis late in the clinical course of untreated Lyme disease.

These antibody responses are paradoxical, given the conclusive evidence demonstrating that B. burgdorferi transmitted to the mammalian host expresses little or no OspA.

The parallel occurrence of OspA antibodies and arthritic episodes suggests that OspA expression is upregulated during infection with B. burgdorferi.

We hypothesized that this was due to the inflammatory environment caused by the immune response to the spirochete. To test our hypothesis, we adapted an in vivo model that mimics the host-pathogen interaction. Dialysis chambers containing B. burgdorferi were implanted into the peritoneal cavities of mice in the presence or absence of zymosan, a yeast cell wall extract that induces inflammation. Spirochetes were harvested 2 days later, and OspA expression was assessed at the protein and transcription level by Western blotting and real-time reverse transcription-PCR, respectively.

Flow cytometry was also utilized to evaluate OspA protein expression on individual spirochetes.

B. burgdorferi maintained in an inflammatory in vivo environment show an increased OspA expression relative to B. burgdorferi kept under normal in vivo conditions. Furthermore, host-adapted B. burgdorferi with a low OspA phenotype upregulates OspA expression when transferred to an inflammatory in vivo environment.

The results obtained by these techniques uniformly identify inflammation as a mediator of in vivo OspA expression in host-adapted B. burgdorferi, providing insights into the behavior of live spirochetes in the mammalian host.

PMID: 12819088 [PubMed - indexed for MEDLINE]

[I think Crowley is suggesting that a period of inflammation would be the most opportune time to test for Bb because OspA, 30-31 kDa, is one of the most specific bands.
Interestingly, CDC recognizes band 30 but not band 31. Crowley seems to think they are the same expression of OspA antibodies, as does Lida Mattman author of "Stealth Pathogens."]

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LymeEnigma
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Re: HOST ADAPTED BORRELIA

Post by LymeEnigma » Sun 28 Oct 2007 18:48

Great articles! I think I may have to bookmark a few of these ... and then read them a few dozen more times. What a complex bacterium!!!

cave76
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Re: HOST ADAPTED BORRELIA

Post by cave76 » Sun 28 Oct 2007 21:28

Hi there, Lyme Enigma :D

kelmo
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Re: HOST ADAPTED BORRELIA

Post by kelmo » Sun 28 Oct 2007 21:33

Hello Cavey!

Martian
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Re: HOST ADAPTED BORRELIA

Post by Martian » Sun 28 Oct 2007 22:05

Aww..

Group Hug!

:mrgreen:

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