Showing posts with label Persister cells. Show all posts

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.

Bijaya Sharma1,

Autumn V. Brown1,

Nicole E. Matluck1,

Linden T. Hu2and

Kim Lewis1 *

+Author Affiliations

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

http://lookingatlyme.blogspot.co.uk/2014/06/cdc-webinar-on-lyme-disease-persistence.html

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.”

http://www.northeastern.edu/news/2015/06/researchers-discovery-may-explain-difficulty-in-treating-lyme-disease/

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

https://www.youtube.com/watch?v=89MdHzNHGZI&list=UUComKOHir2WrDuRZXP8DT-A

Uncultured Bacteria - 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

http://www.bbc.co.uk/news/health-32701896

and earlier http://www.bbc.co.uk/news/health-30657486

Lyme Life written in 2009

I started suffering with arthritis in mainly my large joints especially my knees 6 years ago. The symptoms varied and I remember saying that every joint was affected except my elbows to one doctor. I was told it would be hormonal and to take the usual supplements cod liver oil or glucosamine ( I would certainly recommend buying shares in the companies producing these supplements) They had no noticeable affect.

All my symptoms deteriorated significantly over a few weeks,4 years ago. Hips shoulders and knees being the worst and I started with muscle weakness in upper arms and upper legs. I had difficulty standing and walking across a room. I was unable to walk upstairs and my husband was making plans to convert to a downstairs bedroom. I had seen 5 doctors and 3 Rheumatologists and put on steroids for Poly Myalgia Rheumatica diagnosis. I had been diagnosed with Fibromyalgia and ME/CFS.

I have X rays and scans showing signs of osteoarthritis and Rheumatoid arthritis. ( later note.- the X rays done some years into treatment showed my hands completely normal no signs of inflammation or RA confirming how they felt - normal) I have been retired early from the Civil Service having lost my job not to mention my earning potential. My illness seemed to progress through my body not affecting the same joints left to right at the same time. I had bursitis in left hip, right hip, left elbow. I had synovial thickening in both wrists. At that time I could not lift and hold a magazine so lifting a kettle I could only do if a third full and with two hands. Each joint in my hands fingers feet and toes were affected. I had swallowing difficulties and many other symptoms. None of this describes the endless and awful pain whenever I moved or the tiredness but inability to get quality sleep.

Two years ago my GP gave me Amoxicilin for a sinus/throat/chest infection. All my arthritis symptoms improved. The course ended the symptoms deteriorated I started a second course the symptoms improved. The improvement was more significant than when I had started taking steroids. This led my GP to suspect Lyme Disease. I laughed because we do not travel abroad but she said they had had other cases in the surgery in the early stages of tick bite and Erythma Migrans rash. She said but you have not had a bite. I said oh yes I have I had two on my ankles with rashes, March 05 this was confirmed on her computer when I had seen a locum doctor. My worst symptoms were waking up feeling rigid and having to painfully flex every joint in my body before struggling to get up. The only other time I had experienced this was in May 2003 during a flu like illness like no other I had ever experienced. At that time I had a bite and similar rash on my right foot which lasted like the other rashes about four weeks. I had also consulted the surgery and it was dismissed as a virus. I walked our dog daily in the woods adjacent to our house where the deer roam, prime tick area. Thus started my very lengthy search about Lyme Disease leading me through Lyme Disease Action to a doctor who specialises in this illness. He confirmed my GP's suspicions. I never had a positive blood test but then they are antigen tests and there is much research that shows they are unreliable. In my case the year of steroids and many weeks antibiotics could have affected the results. So with a clinical diagnosis and following ILADS International Lyme and Associated Disease Society guidelines I continued on antibiotics for two years. Both my doctors continued to treat me despite of Health Protection Agency advising against long term antibiotics. I am now nearly 100% recovered I have no pain or muscle weakness. I can walk upstairs something I could not do for three and a half years. I can garden do house work and live a normal life. I still need to pace myself and with only a few months to 60 will not be looking to return to work. Life is such a joy. Sadly there is much controversy about Lyme Disease and doctors in UK are taught that it is so rare. Well where I live in Guildford I have been in contact with a dozen other people with it so perhaps not so rare as HPA would like us to believe. I am in touch with nearly 2000 other patients through a chat line Eurolyme most had been misdiagnosed with several other illnesses. Look at UK charity Lyme Disease Action if you want to read more about this illness. There are many MP's taking an interest in the problems surrounding diagnosis and treatment see above charity links into a recent meeting at the House of Commons.

Thank goodness there are some thinking doctors around who have courageously treated me against opposition and I have made such a miraculous recovery albeit rather a lengthy one. One day there will be many more people who are helped with their chronic illnesses when IDSA starts taking note of what our courageous LLMD’s are doing following ILADS Guidelines.

ME/CFS, Fibromyalgia, Poly Myalgia Rheumatica, Arthritis, Bell’s Palsy, MS,MN, ALS, Parkinson’s, Alzheimer’s, Heart Block, Stroke, Psychiatric, gastric problems the list is endless. Not all suffering from Lyme Borrelia but how many are even properly assessed for it.

UPDATE

UPDATE 10 January 2012