Borrelia burgdorferi, the Causative Agent of Lyme Disease, Forms Drug-Tolerant Persister Cells

@article{Sharma2015BorreliaBT,
  title={Borrelia burgdorferi, the Causative Agent of Lyme Disease, Forms Drug-Tolerant Persister Cells},
  author={B. Sharma and Autumn V Brown and Nicole Matluck and Linden T Hu and K. Lewis},
  journal={Antimicrobial Agents and Chemotherapy},
  year={2015},
  volume={59},
  pages={4616 - 4624}
}
Borrelia burgdorferi is the causative agent of Lyme disease, which affects an estimated 300,000 people annually in the United States. [...] Key Result Killing growing cultures of B. burgdorferi with antibiotics used to treat the disease was distinctly biphasic, with a small subpopulation of surviving cells. Upon regrowth, these cells formed a new subpopulation of antibiotic-tolerant cells, indicating that these are persisters rather than resistant mutants.Expand
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It is demonstrated that noncultivable spirochetes can persist in a host following antimicrobial treatment for a long time but did not demonstrate their clinical relevance in a mouse model of chronic infection. Expand
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Examination of the action of antibiotics in severe combined immunodeficient mice showed that doxycycline, a standard of care for uncomplicated acute infection, did not clear the pathogen, and both ceftriaxone and vancomycin cleared the infection. Expand
Lyme Neuroborreliosis: Mechanisms of B. burgdorferi Infection of the Nervous System
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The molecular mechanisms of spirochete entry into the brain and the role B. burgdorferi sensu stricto genotypes play in CNS infectivity are explored and understanding infectivity can provide therapeutic targets for LNB treatment and offer public health understanding of the B. burglorferi Sensu stricta genotypes that cause long-lasting symptoms. Expand
Identification of Additional Anti-Persister Activity against Borrelia burgdorferi from an FDA Drug Library
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Interestingly, drugs used for treating other non-infectious conditions including verteporfin, oltipraz, pyroglutamic acid, pidolic acid, and dextrorphan tartrate, that act on the glutathione/γ-glutamyl pathway involved in protection against free radical damage, and also the antidepressant drug indatraline, were found to have high activity against stationary phase B. burgdorferi. Expand
Azlocillin can be the potential drug candidate against drug-tolerant Borrelia burgdorferi sensu stricto JLB31
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Findings strongly suggests that azlocillin can be effective in treating B. burgdorferi sensu stricto JLB31 infection and furthermore in depth research is necessary to evaluate its potential use for Lyme disease therapy. Expand
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TLDR
Cefuroxime (Ceftin), the third commonly used and most active antibiotic to treat Lyme disease, could replace cefoperazone (a drug no longer available in the US) in the daptomycin + doxycycline combination with complete eradication of the biofilm-like structures as shown by lack of any regrowth in subcultures. Expand
Identification of new drug candidates against Borrelia burgdorferi using high-throughput screening
TLDR
There is unmet need for developing the therapeutic agents that focus on removing the persisting bacterial form of B. burgdorferi in rodent and nonhuman primates, and high-throughput screening was done using BacTiter-Glo assay for four compound libraries to identify candidates that stop the growth of B., burgdorFERi in vitro. Expand
The Clinical Relevance of Studies on Borrelia burgdorferi Persisters.
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The results of 5 clinical trials failed to provide evidence of convincing clinical benefit or that the risk/benefit ratio favored this therapeutic approach, which suggests that persistent symptoms are often reversible. Expand
Persistent Borrelia Infection in Patients with Ongoing Symptoms of Lyme Disease
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Using multiple corroborative detection methods, it is shown that patients with persistent Lyme disease symptoms may have ongoing spirochetal infection despite antibiotic treatment, similar to findings in non-human primates. Expand
Proteomic Analyses of Morphological Variants of Borrelia burgdorferi Shed New Light on Persistence Mechanisms: Implications for Pathogenesis, Diagnosis and Treatment
TLDR
It is shown that the two separated stationary phase forms especially microcolony form have more persistence to antibiotics than the log phase spirochetal form and a particularly interesting observation is that infection and virulence related proteins are highly up-regulated in stationary phase planktonic form and microcolonies form compared with log phaseSpirocheta form. Expand
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