Borrelia burgdorferi, the causative agent of Lyme disease, forms drug-tolerant persister cells.
- Bijaya Sharma1,
- Autumn V. Brown1,
- Nicole E. Matluck1,
- Linden T. Hu2and
- Kim Lewis1*
1Department of Biology, Northeastern University, Boston, Massachusetts, USA
2Department of Medicine, Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, Massachusetts, USA.
ABSTRACT
Borrelia burgdorferi is the causative agent of Lyme disease, which affects an estimated 300,000 people annually in the US. When treated early, the disease usually resolves, but left untreated, 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 of growing cultures of B. burgdorferiwith 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 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 anti-cancer agent that forms adducts with DNA, killed persisters and eradicated both 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 antibiotic was added again. Four pulse-doses of ceftriaxone killed persisters, eradicating all live bacteria in the culture.
http://aac.asm.org/content/early/2015/05/20/AAC.00864-15.abstract
Earlier post with vimeo of Prof Lewis as well as CDC Webinar
Good to see Dr Linden T Hu working with Prof Lewis - Dr. Linden Hu, Tufts University
Borrelia burgdorferi Persistence: Consensus and Controversy – where do we go from here? This was presented in CDC Webinar on persistence see link above.
Other videos of Prof Lewis Principles of Antibiotic Discovery – Kim Lewis
Uncultured Bacteria – Kim Lewis
Source:
http://lookingatlyme.blogspot.com/2015/05/borrelia-burgdorferi-lyme-disease-forms.html
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