Persistence of Borrelia burgdorferi following Antibiotic Treatment in Mice

Center for Comparative Medicine, School of Medicine, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA.
Antimicrobial Agents and Chemotherapy (Impact Factor: 4.45). 06/2008; 52(5):1728-36. DOI: 10.1128/AAC.01050-07
Source: PubMed

ABSTRACT The effectiveness of antibiotic treatment was examined in a mouse model of Lyme borreliosis. Mice were treated with ceftriaxone or saline solution for 1 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, PCR, xenodiagnosis, and transplantation of allografts at 1 and 3 months after completion of treatment. In addition, tissues were examined for the presence of spirochetes by immunohistochemistry. In contrast to saline solution-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 on by Ixodes scapularis ticks (xenodiagnosis), spirochetes were acquired by the ticks, as determined based upon PCR results, 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 nondividing but infectious spirochetes, particularly when antibiotic treatment was commenced during the chronic stage of infection.

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    • "A population-based, retrospective cohort study of individuals with a history of LD revealed that they were significantly more likely to have joint pain, memory impairment, and poor functional status due to pain than persons without a history of LD, even though there were no signs of objective findings on physical examination or neurocognitive testing [10]. Two recent mouse studies revealed that spirochetes persist despite antibiotic therapy and that standard diagnostic tests are not able to detect their presence [11] [12]. In sum, there are no clinical or laboratory markers that identify the eradication of the pathogen. "
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    ABSTRACT: The evidence continues to mount that Chronic Lyme Disease (CLD) exists and must be addressed by the medical community if solutions are to be found. Four National Institutes of Health (NIH) trials validated the existence and severity of CLD. Despite the evidence, there are physicians who continue to deny the existence and severity of CLD, which can hinder efforts to find a solution. Recognizing CLD could facilitate efforts to avoid diagnostic delays of two years and durations of illness of 4.7 to 9 years described in the NIH trials. The risk to society of emerging antibiotic-resistant organisms should be weighed against the societal risks associated with failing to treat an emerging population saddled with CLD. The mixed long-term outcome in children could also be examined. Once we accept the evidence that CLD exists, the medical community should be able to find solutions. Medical professionals should be encouraged to examine whether: (1) innovative treatments for early LD might prevent CLD, (2) early diagnosis of CLD might result in better treatment outcomes, and (3) more effective treatment regimens can be developed for CLD patients who have had prolonged illness and an associated poor quality of life.
    Interdisciplinary Perspectives on Infectious Diseases 05/2010; 2010:876450. DOI:10.1155/2010/876450
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    • "Borrelia spp. are capable of persistent infection, and such persistence is the norm in mice, rats, hamsters, dogs, and monkeys (Barthold 2000; Straubinger 2000; Summers et al. 2005; Hodzic et al. 2008). Persistence in reservoir hosts can be interpreted as an evolutionarily shaped survival strategy linked to the asynchronous phenology of the tick vectors (Kurtenbach et al. 2006). "
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    ABSTRACT: Lyme borreliosis (LB), also known as Lyme disease, is emerging as a serious tick-borne illness across Canada. More than three decades of research on LB in North America and Europe have provided a large, complex body of research involving well-documented difficulties at several levels. However, entomologists are well situated to contribute to resolving some of these challenges. The central pathogen in LB, the spirochete Borrelia burgdorferi Johnson et al., includes numerous genospecies and strains that are associated with different disease symptoms and distributions. The primary vectors of LB are ticks of various Ixodes Latreille species (Acari: Ixodida: Ixodidae), but questions linger concerning the status of a number of other arthropods that may be infected with B. burgdorferi but do not transmit it biologically. A variety of vertebrates may serve as reservoirs for LB, but differences in their ability to transmit LB are not well understood at the community level. Persistent cystic forms of and immune-system evasion by B. burgdorferi contribute to extraordinary challenges in diagnosing LB. Multiple trade-offs constrain the effectiveness of assays like ELISA, Western blot, polymerase chain reaction, and microscopic visualization of the spirochetes. Consequently, opportunities abound for entomologists to contribute to documenting the diversity of the players and their interactions in this devilishly complex disease.
    The Canadian Entomologist 12/2009; 141(6):521-549. DOI:10.4039/n08-CPA04 · 0.67 Impact Factor
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    • "Given the growing appreciation that bacterial aggregation is of biological significance, Borrelia aggregation deserves further study. B. burgdorferi persists after antibiotic treatment in mice (Hodzic et al. 2008), and there are conflicting reports about the effectiveness of antibiotic therapy in human Lyme disease (Moody et al. 1994, Nowakowski et al. 1995, Wang et al. 1998). In Pseudomonas aeruginosa aggregation has been linked to persistence and antibiotic resistance in cystic fibrosis patients (Drenkard and Ausubel 2002). "
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    ABSTRACT: Lyme disease is caused by the tick-borne spirochete, Borrelia burgdorferi. It has been documented that B. burgdorferi form aggregates within ticks and during in vitro culture. However, Borrelia aggregates remain poorly characterized, and their functional significance is unknown. Here we have characterized Borrelia aggregates using microscopy and flow cytometry. Borrelia aggregation was temperature, pH, and growth phase dependent. Environmental conditions (high temperature, low pH, and high cell density) favorable for aggregation were similar to the conditions that increased the expression of B. burgdoferi genes, such as outer surface protein C (ospC), that are regulated by the RpoN/RpoS sigma factors. Experiments were conducted to determine if there is a relationship between aggregation and gene regulation through the RpoN/RpoS pathway. ospC Transcript levels were similar between aggregates and free cells. Moreover, no differences were observed in aggregate formation when null mutants of rpoS, rpoN, or ospC were compared to wild-type spirochetes. These results indicated that, despite the similar external signals that promoted aggregation and the RpoN/RpoS pathway, the two processes were not linked at the molecular level. The methods developed here to study B. burgdorferi aggregates will be useful for further studies on spirochete aggregates.
    Vector borne and zoonotic diseases (Larchmont, N.Y.) 07/2009; 9(3):323-9. DOI:10.1089/vbz.2008.0148 · 2.53 Impact Factor
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