ArticleAntimicrobial agents and chemotherapy2015
Borrelia burgdorferi, the Causative Agent of Lyme Disease, Forms Drug-Tolerant Persister Cells.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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102 citing papers in PubMed.
- A lipid compendium of a metabolically compromised bacterium provides insights into lipid acquisition, biosynthesis, and metabolism.bioRxiv : the preprint server for biology · 2026Article
- Epidemiology, diagnosis and emerging therapies for Lyme disease of the Northern Hemisphere.International journal of emergency medicine · 2026Review
- Ιdentification of SQ109 analogs with enhanced antimicrobial activity against methicillin-resistantAntimicrobial agents and chemotherapy · 2026Article
- A natural barrier: tick-repellent potential of a spruce-derived volatile blend against Hyalomma excavatum and Ixodes ricinus.Pest management science · 2026Article
- Molecular Basis of Persister Awakening and Lag-Phase Recovery inInternational journal of molecular sciences · 2026Review
- Aspects of the Immunopathogenesis of Lyme Arthritis.Microorganisms · 2025Review
- The Next Frontier: Unveiling Novel Approaches for Combating Multidrug-Resistant Bacteria.Pharmaceutical research · 2025Review
- A high-resolution screen identifies a preexisting beta-lactam that specifically treats Lyme disease in mice.Science translational medicine · 2025Article
- Article
- Systematic design of pulse dosing to eradicate persister bacteria: The case of fluoroquinolones.Computers & chemical engineering · 2025Article
- Article
- Lactate dehydrogenase is the Achilles' heel of Lyme disease bacteriumbioRxiv : the preprint server for biology · 2025Article
- A pilot study of disulfiram for individuals with persistent symptoms despite prior antibiotic treatment for Lyme disease.Frontiers in medicine · 2025Article
- Mini review: Persister cell control strategies.Frontiers in pharmacology · 2025Review
- Intracellular ATP concentration is a key regulator of bacterial cell fate.Journal of bacteriology · 2024Article
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- Bacterial persisters: molecular mechanisms and therapeutic development.Signal transduction and targeted therapy · 2024Review
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- Current and emerging approaches for eliminatingFrontiers in microbiology · 2024Review
- Screening Marine Microbial Metabolites as Promising Inhibitors ofBioMed research international · 2024Article
42 more citing papers are in PubMed but not listed here.
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5 authors.
Funding
Abstract
Borrelia burgdorferi is the causative agent of Lyme disease, which affects an estimated 300,000 people annually in the United States. When treated early, the disease usually resolves, but when left untreated, it can result in symptoms such as arthritis and encephalopathy. Treatment of the late-stage disease may require multiple courses of antibiotic therapy. Given that antibiotic resistance has not been observed for B. burgdorferi, the reason for the recalcitrance of late-stage disease to antibiotics is unclear. In other chronic infections, the presence of drug-tolerant persisters has been linked to recalcitrance of the disease. In this study, we examined the ability of B. burgdorferi to form persisters. 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. The level of persisters increased sharply as the culture transitioned from the exponential to stationary phase. Combinations of antibiotics did not improve killing. Daptomycin, a membrane-active bactericidal antibiotic, killed stationary-phase cells but not persisters. Mitomycin C, an anticancer agent that forms adducts with DNA, killed persisters and eradicated growing and stationary cultures of B. burgdorferi. Finally, we examined the ability of pulse dosing an antibiotic to eliminate persisters. After addition of ceftriaxone, the antibiotic was washed away, surviving persisters were allowed to resuscitate, and the antibiotic was added again. Four pulse doses of ceftriaxone killed persisters, eradicating all live bacteria in the culture.
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