Comparison of in vitro activities of tigecycline, doxycycline, and tetracycline against the spirochete Borrelia burgdorferi

Ates, Louis S.; Hanssen-Hübner, Christa; Norris, Douglas E.; Richter, D.; Kraiczy, Peter; Hunfeld, Klaus Peter

doi:10.1016/j.ttbdis.2009.11.004

Cited by 25 publications

(39 citation statements)

References 29 publications

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“…This result is consistent with a previous study, which determined that tetracycline is more active than doxycycline in a minimum bactericidal concentration test. 35 Consistent with this finding, we observed that most cells in the stationary-phase B. burgdorferi cultures treated with tetracycline had round-body forms (Figure 3I), in contrast to stationary-phase B. burgdorferi cultures treated with doxycycline, which remained in spirochetal form (Figure 3B). B. burgdorferi can form different morphological shapes in the stationary phase or under adverse conditions, and tetracycline may be ineffective against some cell morphologies, such as round bodies (cysts).…”

Section: Discussionsupporting

confidence: 84%

Identification of novel activity against Borrelia burgdorferi persisters using an FDA approved drug library

Feng

Wang

Shi

et al. 2014

Emerging Microbes & Infections

112

234

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Although antibiotic treatment for Lyme disease is effective in the majority of cases, especially during the early phase of the disease, a minority of patients suffer from post-treatment Lyme disease syndrome (PTLDS). It is unclear what mechanisms drive this problem, and although slow or ineffective killing of Borrelia burgdorferi has been suggested as an explanation, there is a lack of evidence that viable organisms are present in PTLDS. Although not a clinical surrogate, insight may be gained by examining stationary-phase in vitro Borrelia burgdorferi persisters that survive treatment with the antibiotics doxycycline and amoxicillin. To identify drug candidates that can eliminate B. burgdorferi persisters more effectively, we screened an Food and Drug Administration (FDA)-approved drug library consisting of 1524 compounds against stationary-phase B. burgdorferi by using a newly developed high throughput SYBR Green I/propidium iodide (PI) assay. We identified 165 agents approved for use in other disease conditions that had more activity than doxycycline and amoxicillin against B. burgdorferi persisters. The top 27 drug candidates from the 165 hits were confirmed to have higher anti-persister activity than the current frontline antibiotics. Among the top 27 confirmed drug candidates from the 165 hits, daptomycin, clofazimine, carbomycin, sulfa drugs (e.g., sulfamethoxazole), and certain cephalosporins (e.g. cefoperazone) had the highest anti-persister activity. In addition, some drug candidates, such as daptomycin and clofazimine (which had the highest activity against non-growing persisters), had relatively poor activity or a high minimal inhibitory concentration (MIC) against growing B. burgdorferi. Our findings may have implications for the development of a more effective treatment for Lyme disease and for the relief of long-term symptoms that afflict some Lyme disease patients.

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Section: Discussionsupporting

confidence: 84%

Identification of novel activity against Borrelia burgdorferi persisters using an FDA approved drug library

Feng

Wang

Shi

et al. 2014

Emerging Microbes & Infections

112

234

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“…daily is prescribed to treat Lyme disease. We did not determine the MIC of the borrelial strains utilized in this study to ceftriaxone, but in other studies with the same strains the MIC values ranged from 0.025 to 12 g/ml (14,(30)(31)(32).…”

Section: Discussionmentioning

confidence: 85%

Detection of Borrelia burgdorferi Nucleic Acids after Antibiotic Treatment Does Not Confirm Viability

et al. 2013

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The persistence of dormant, noncultivable Borrelia burgdorferi after ceftriaxone treatment was examined. B. burgdorferi isolates were cultivated in Barbour-Stoenner-Kelly medium in the presence or absence of ceftriaxone, and cultures were monitored for up to 56 days. Viability of B. burgdorferi was assessed by subculture, growth, morphology, and pH (as a surrogate for metabolic activity). In addition, the presence of B. burgdorferi DNA and mRNA was assayed by PCR and by real-time reverse transcription (RT)-PCR, respectively. Spirochetes could not be successfully subcultured by day 3 after exposure to ceftriaxone. In cultures treated with ceftriaxone, the pH of the culture medium did not change through day 56, whereas it declined by at least 1 pH unit by 14 days in untreated cultures. These results suggest that B. burgdorferi viability is rapidly eliminated after antibiotic treatment. Nevertheless, DNA was detected by B. burgdorferi-specific PCR for up to 56 days in aliquots from both ceftriaxone-treated and untreated cultures. In addition, although ceftriaxone treatment resulted in a reduction in the quantities of transcript for ospC, ospA, flaB, and pfk, certain mRNAs could be detected through day 14. Transcript for all 4 genes was essentially undetectable after 28 days of treatment. Taken together, the results suggest that B. burgdorferi DNA and mRNA can be detected in samples long after spirochetes are no longer viable as assessed by classic microbiological parameters. PCR positivity in the absence of culture positivity following antibiotic treatment in animal and human studies should be interpreted with caution.

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“…These field isolates included: 1 strain ( B . burgdorferi ss UCSC) belonging to a tourist from Venezuela and characterized in previous studies by molecular and conventional methods [1], [26]–[28] and 5 field isolates from different sources [29]–[31], namely B . burgdorferi ZS7 (tick isolate, Germany), B .…”

Section: Methodsmentioning

confidence: 99%

Identification of Borrelia Species after Creation of an In-House MALDI-TOF MS Database

et al. 2014

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Lyme borreliosis (LB) is a multisystemic disease caused by Borrelia burgdorferi sensu lato (sl) complex transmitted to humans by Ixodes ticks. B. burgdorferi sl complex, currently comprising at least 19 genospecies, includes the main pathogenic species responsible for human disease in Europe: B. burgdorferi sensu stricto (ss), B. afzelii, and B. garinii. In this study, for the first time, MALDI-TOF MS was applied to Borrelia spp., supplementing the existing database, limited to the species B. burgdorferi ss, B . spielmanii and B. garinii, with the species B. afzelii, in order to enable the identification of all the species potentially implicated in LB in Europe. Moreover, we supplemented the database also with B. hermsii, which is the primary cause of tick-borne relapsing fever in western North America, B. japonica, circulating in Asia, and another reference strain of B. burgdorferi ss (B31 strain). The dendrogram obtained by analyzing the protein profiles of the different Borrelia species reflected Borrelia taxonomy, showing that all the species included in the Borrelia sl complex clustered in a unique branch, while Borrelia hermsii clustered separately. In conclusion, in this study MALDI-TOF MS proved a useful tool suitable for identification of Borrelia spp. both for diagnostic purpose and epidemiological surveillance.

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Comparison of in vitro activities of tigecycline, doxycycline, and tetracycline against the spirochete Borrelia burgdorferi

Cited by 25 publications

References 29 publications

Identification of novel activity against Borrelia burgdorferi persisters using an FDA approved drug library

Identification of novel activity against Borrelia burgdorferi persisters using an FDA approved drug library

Detection of Borrelia burgdorferi Nucleic Acids after Antibiotic Treatment Does Not Confirm Viability

Identification of Borrelia Species after Creation of an In-House MALDI-TOF MS Database

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