Borrelia burgdorferi, the causative agent of Lyme disease, forms drug-tolerant persister cells.
+Author Affiliations
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
https://www.youtube.com/watch?v=-ojRvlwanSA
What lights my fire https://www.youtube.com/watch?v=GBZ9hyrMsoM
Prof Lewis featured in a recent BBC documentary on Panorama on his research into finding new antibiotics
and earlier http://www.bbc.co.uk/news/health-30657486
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
ReplyDeleteNot 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.
DeleteNew study on persister cells by Zhang now Joanne-Hilary
ReplyDeleteYes 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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