Friday, 29 May 2015

BORRELIA BURGDORFERI - LYME DISEASE FORMS DRUG TOLERANT PERSISTER CELLS

Borrelia burgdorferi, the causative agent of Lyme disease, forms drug-tolerant persister cells.

  1. Kim Lewis1*
+Author Affiliations
  1. 1Department of Biology, Northeastern University, Boston, Massachusetts, USA
  2. 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.


Researchers’ discovery may explain difficulty in treating Lyme disease - 

This is the first time, we think, that pulse-​​dosing has been pub­lished as a method for erad­i­cating the pop­u­la­tion of a pathogen with antibi­otics that don’t kill dor­mant cells,” Lewis said. “The trick to doing this is to allow the dor­mant cells to wake up.”

He added: “This gives you an idea that you could, in prin­ciple, estab­lish a sim­ilar reg­i­ment for treating patients for this and other chronic diseases.”

Other videos of Prof Lewis Principles of Antibiotic Discovery - Kim Lewis 

Uncultured Bacteria - Kim Lewis 
https://www.youtube.com/watch?v=-ojRvlwanSA


Prof Lewis featured in a recent BBC documentary on Panorama on his research into finding new antibiotics 


4 comments:

  1. Wow!So according to this abstract, we may have had the antibiotic cure to Lyme all along,it's just the way it is administered that would make all the difference.I really hope this proves true and everyone can access it-Hilary

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    1. Not quite so simple though because this research was in vitro and in vivo is quite another ball game especially when the bacteria has had years to disseminate throughout the body into areas where antibiotics don't easily penetrate but nevertheless exciting news and one which supports much of what many Lyme doctors have learnt and developed over many years, - tritherapy and pulsed doses.

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  2. New study on persister cells by Zhang now Joanne-Hilary

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    1. Yes thanks Hilary posted last night - exciting times, need more research and more details of new tests that Fallon says sound promising.

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