Persistence of Bb after antibiotic treatment (murine model)

Topics with information and discussion about published studies related to Lyme disease and other tick-borne diseases.
rlstanley
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Persistence of Bb after antibiotic treatment (murine model)

Post by rlstanley » Tue 4 Mar 2008 21:51

http://aac.asm.org/cgi/content/abstract/AAC.01050-07v1

Persistence of Borrelia burgdorferi Following Antibiotic Treatment in Mice

Emir Hodzic, Sunlian Feng, Kevin Holden, Kimberly J. Freet, and Stephen W. Barthold*
Center for Comparative Medicine, Schools of Medicine and Veterinary Medicine, University of California at Davis, One Shields Avenue, Davis, CA 95616

* To whom correspondence should be addressed: Email: swbarthold@ucdavis.edu

Abstract

The effectiveness of antibiotic treatment was examined in a mouse model of Lyme borreliosis.

Mice were treated with ceftriaxone or saline for one month, commencing during the early (3 weeks) or chronic (4 months) stages of infection with Borrelia burgdorferi. Tissues from mice were tested for infection by culture, polymerase chain reaction (PCR), xenodiagnosis, and transplantation of allografts at 1 and 3 months after completion of treatment. In addition, tissues were examined for spirochetes by immunohistochemistry.

In contrast to saline-treated mice, mice treated with antibiotic were consistently culture-negative, but tissues from some of the mice remained PCR-positive, and spirochetes could be visualized in collagen-rich tissues.

Furthermore, when some of the antibiotic treated mice were fed upon by Ixodes scapularis ticks (xenodiagnosis), spirochetes were acquired by the ticks, based upon PCR, and ticks from those cohorts transmitted spirochetes to naïve SCID mice, which became PCR-positive, but culture-negative.

Results indicated that following antibiotic treatment, mice remained infected with non-dividing but infectious spirochetes, particularly when antibiotic treatment was commenced during the chronic stage of infection.
Last edited by rlstanley on Fri 7 Mar 2008 0:23, edited 1 time in total.

cave76
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Re: Persistence of Bb after antibiotic treatment (murine model)

Post by cave76 » Wed 5 Mar 2008 0:52

***mice remained infected with non-dividing but infectious spirochetes****

Rita, do you (or anyone else) know what 'non-dividing' means. A member of this forum asked that question on The Other Forum. I hope someone can explain it. I've asked her to send the entire article IF she can. That may not be possible, I guess.

Martian
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Re: Persistence of Bb after antibiotic treatment (murine model)

Post by Martian » Wed 5 Mar 2008 1:44

cave76 wrote:***mice remained infected with non-dividing but infectious spirochetes****

Rita, do you (or anyone else) know what 'non-dividing' means.
Makes me wonder too.

Perhaps encysted Bb, since ceftriaxone is "notorious" for inducing the formation of cyst forms. But it could also be just normal Bb who "thought" they'd better not divide when ceftriaxone is around them. As long as they do not divide, ceftriaxone will not harm them. That's yet another drawback of the "miracle" drug..

rlstanley
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Joined: Mon 3 Dec 2007 2:53

Re: Persistence of Bb after antibiotic treatment (murine model)

Post by rlstanley » Wed 5 Mar 2008 2:41

Get the article and see how they define non-dividing. I've Googled this, and it am not sure at this point in time.

I also have a call out on a professional board to see about answering this important question. I'll give you the feedback.

Rita

cave76
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Re: Persistence of Bb after antibiotic treatment (murine model)

Post by cave76 » Wed 5 Mar 2008 4:39

http://iai.asm.org/cgi/reprint/74/4/2468.pdf

Human Neutrophil Calprotectin Reduces the Susceptibility of
Borrelia burgdorferi to Penicillin


(not an answer but maybe a clue to an answer)


****In our studies, we noted that
when B. burgdorferi was exposed to a physiological concentration
of calprotectin, spirochetes entered a static, nondividing
state but were not directly killed.

A natural consequence of
growth inhibition is that such organisms are no longer sensitive
to antibiotics that target dividing organisms.

We have investigated
whether the nondividing state of spirochetes in calprotectin,
such as may occur in an inflamed joint, renders them
less susceptible to killing by therapeutic doses of certain antibiotics.*****

rlstanley
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Re: Persistence of Bb after antibiotic treatment (murine model)

Post by rlstanley » Wed 5 Mar 2008 16:46

Excerpt from the paper being discussed in this thread Persistence of Borrelia burgdorferi Following Antibiotic Treatment in Mice:
“Normally, there is a burst of spirochetal replication in ticks following feeding, with a net increase in DNA copy numbers (21). This was not seen in ticks that fed upon antibiotic-treated mice, in contrast to ticks that fed uponsaline-treated control mice. Notably, C3H-scid mice developed disseminated infections when fed upon by ticks infected with spirochetes from antibiotic-treated mice, but spirochetes could not be cultured from the C3H-scid mice, and DNA copy numbers in tissues were generally low.

These results support the notion that spirochetes were infectious, but attenuated in their ability to replicate, even in globally immunodeficient hosts.”

cave76
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Re: Persistence of Bb after antibiotic treatment (murine model)

Post by cave76 » Wed 5 Mar 2008 16:55

Thanks Rita,

Attenuate:

2. To reduce in force, value, amount, or degree; weaken: Medicine attenuated the fever's effect.
3. To lessen the density of; rarefy.
4. Biology To make (bacteria or viruses) less virulent.

Martian
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Re: Persistence of Bb after antibiotic treatment (murine model)

Post by Martian » Wed 5 Mar 2008 22:10

Here is an article with some comments from Stephen Barthold, one of the authors of the study in question. I have emphasized an interesting passage, which is related to this topic.

Quoting source: http://www.ucdmc.ucdavis.edu/ucdavismed ... res/3.html
LINKING HUMAN ANIMAL BIOMEDICAL RESEARCH TO BENEFIT BOTH

No one knew what Lyme disease was when Stephen Barthold's daughter was diagnosed with it in 1978. At the time, Barthold and his family were living in Connecticut, the state where the cause of the tickborne disease would be identified four years later.

While a course of antibiotics for an unrelated infection cured his daughter, the father remained intrigued. Today, with 30 years of research and more than 100 papers on Lyme disease under his belt, Barthold, a veterinary pathologist with a joint appointment in the schools of Medicine and Veterinary Medicine, is recognized as one of the leading authorities on how the Lyme bacterium interacts with the hosts it infects.

When he arrived at UC Davis in 1997, Barthold lost no time in creating an ideal home for the kind of interdisciplinary work his research program requires: UC Davis Center for Comparative Medicine.

Housed on the west side of the Davis campus, the unique teaching and research complex draws faculty from the schools of Medicine and Veterinary Medicine to focus on infectious disease and cancer research.

"We take advantage of the concept of ‘one medicine.' That is, since nearly every human disease has an animal counterpart, what we learn from one benefits the other," explains Barthold, who was recruited from Yale School of Medicine to become the center's founding director.

With 23,305 human cases reported to the CDC in 2005, Lyme disease is now the most common vector-borne disease in the United States. Infection is very common among domestic animals, as well. When treated with antibiotics early, it can usually be eradicated.

But, says Barthold, "our work has shown that in the absence of antibiotic treatment, 100 percent of animals infected with Lyme bacteria remain infected even though they have a perfectly functional immune response."

Working with mice, Barthold has found that the bacteria, Borrelia burgdorferi, "literally integrate themselves into collagen tissue. They colonize little spots here and there: one joint, but not another; nervous tissue; the heart. It varies from individual to individual, which explains the disease's highly variable clinical manifestations."

In a study to be published later this year, Barthold outlines his discovery that even after long-term antibiotic treatment, bacteria hidden in collagen tissue are still viable and infectious. "We're trying to be careful in what we claim," he says, "but these findings will be controversial."


Modern foe; old friend

Jay Solnick is one of the 11 faculty members affiliated with the center. An infectious-disease physician with a joint appointment in the medical school's Internal Medicine and Medical Microbiology departments, Solnick works with rhesus macaques to study the unusual interactions between Helicobacter pylori – the bacterium responsible for stomach ulcers and some stomach cancers – and the primates it colonizes.

A century or two ago, virtually everyone was infected for life by H. pylori, "yet clinical problems were a non-issue then," Solnick explains. Stomach ulcer disease was virtually unknown, and few people ever grew old enough to get stomach cancer.

"Given that you had almost universal colonization with Helicobacter – both in humans and in a range of mammals – it's reasonable to suspect that the bacteria confer some kind of benefit."

What particularly piques Solnick's interest is how the pathogen and the host adapt to each other during the course of a lifelong infection in the stomach, an exceptionally hostile environment. One of his discoveries is that a certain gene cluster in H. pylori's DNA triggers the stomach's mucous lining to step up production of various antimicrobial molecules.

"It's a little bit paradoxical," Solnick says. "The cluster is inherited and Helicobacter pick it up over generations, so we know it must be advantageous. Yet you'd think that triggering an antimicrobial response would work against it."

His theory? While Helicobacter may be resistant to the host's defenses, other bacteria probably are not. "Helicobacter may be trying to carve out its own niche by modulating the competing flora," he says.

Indeed, recent evidence suggests that H. pylori might protect against various ailments, including intestinal diseases, asthma and possibly even cancer of the esophagus.

Solnick is treading on contentious ground. "The GI community is opposed to the idea that Helicobacter has any benefits at all," he says.

Even if he can show that it does, the fact remains that the bacteria cause stomach cancer in 3 percent of the humans they infect.

In response, Solnick and colleagues from UC Davis and Mexico are looking for biomarkers in stored samples of human serum that might correlate with cases of gastric cancer.

"The Holy Grail of Helicobacter research is to find some way of knowing who will eventually get stomach cancer," he says. "If we can do that, we can eradicate the bacteria in those individuals, and that would have a huge impact on human health."

A decade of teaching, research

It's innovative research like Solnick's that the Center for Comparative Medicine was designed to support, says Barthold. In the 10 years since the center opened its doors, its eclectic mix of projects and expertise has created a rich environment for graduate education and biomedical research – a role that's more important now than ever before, he says.

"With 60 percent of NIH funding involving animal counterparts of human disease, there's a need for what we're doing," he says. "Here we're investigating infectious diseases from the human and veterinary medical perspectives in the same building. The center is truly unique."

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LymeEnigma
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Re: Persistence of Bb after antibiotic treatment (murine model)

Post by LymeEnigma » Thu 6 Mar 2008 19:42

Any idea how long these non-dividing Bb are capable of surviving?

rlstanley
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Re: Persistence of Bb after antibiotic treatment (murine model)

Post by rlstanley » Fri 7 Mar 2008 0:27

I think it would be a good idea to read the article to see exactly how the study was done and see the authors' interpretations and conclusions based on the literature and data from the experiments.

I don't have a copy, but I have written to Dr. Barthold and requested a reprint of the article.

His email is given at the top of the abstract.

Rita

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