DRUG ACTIVITIES AGAINST BORRELIA PERSISTERS - LYME DISEASE PERSISTERS

A Drug Combination Screen Identifies Drugs Active against Amoxicillin-induced Round Bodies of Borrelia burgdorferi Persisters from an FDA Drug Library

Jie Feng1, Wanliang Shi1, Shuo Zhang1, David Sullivan1, Paul Auwaerter2 and Ying Zhang1*

• 1Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, USA
• 2Fisher Center for Environmental Infectious Diseases, School of Medicine, Johns Hopkins University, USA

Although currently recommended antibiotics for Lyme disease such as doxycycline or amoxicillin cure the majority of the patients, about 10-20% of patients treated for Lyme disease may experience lingering symptoms including fatigue, pain, or joint and muscle aches. Under stress conditions such as starvation or antibiotic exposure, Borrelia burgdorferi can develop round body forms, which are a type of persister bacteria that are not killed by current Lyme antibiotics. To identify more effective drugs that are active against the round bodies of B. burgdorferi, we established a round body persister model induced by amoxicillin and screened the Food and Drug Administration (FDA) drug library consisting of 1581 drug compounds and also 22 drug combinations using the SYBR Green I/propidium iodide (PI) viability assay. We identified 23 drug candidates that have higher activity against the round bodies of B. burgdorferi than either amoxicillin or doxycycline. Eleven of these scored better than metronidazole and tinidazole which have been previously described to be active against round bodies. While some drug candidates such as daptomycin and clofazimine overlapped with a previous screen against stationary phase B. burgdorferi persisters, additional drug candidates active against round bodies we identified include artemisinin, ciprofloxacin, nifuroxime, fosfomycin, chlortetracycline, sulfacetamide, sulfamethoxypyridazine and sulfathiozole. Two triple drug combinations had the highest activity against round bodies and stationary phase B. burgdorferi persisters: artemisinin/cefoperazone/doxycycline and sulfachlorpyridazine/daptomycin/doxycycline. These findings confirm and extend previous findings that certain drug combinations have superior activity against B. burgdorferi persisters in vitro, even if pre-treated with amoxicillin. These findings may have implications for improved treatment of Lyme disease.

http://journal.frontiersin.org/article/10.3389/fmicb.2016.00743/full 

Links into earlier posts on Prof Zhang research can be found:- 

http://lookingatlyme.blogspot.co.uk/2015/10/lyme-disease-persister-drugs-dr-ying.html

LYME DISEASE PERSISTER DRUGS - DR YING ZHANG

Interview with Prof. Ying Zhang at the NorVect Conference 2015

Published on Sep 29, 2015

Prof Ying Zhang from John Hopkins Bloomberg School of Public Health explains why Lyme disease is so difficult to treat. Having worked with Tuberculosis (TB) for many years, he sees the similarities and differences between these to bacteria. With Tuberculosis it is known that you have to treat with certain drug combinations that kill the growing form and the non-growing form (persisters) and if you treat shorter than 6 months, the patient will get a relapse.

The bacterium that causes Lyme disease is much more advanced than the TB bacterium, and the main reason is that it also takes a persisting form. These persister forms of the Borrelia bacteria cannot be cultured.

The two views – ILADS and IDSA are two different ways of seeing the same disease. Prof. Zhang thinks they are both right. When it comes to acute Lyme disease, IDSA is right. Then you only need shorter courses of treatment. When the disease turns chronic, longer courses of treatment with the right drug combinations are needed (ILADS view).

The full presentation from Dr Zhang is available on the Norvect website from their 2015 conference http://norvect.no/about-norvect/    

From Norvect website -
Talk: Borrelia Persister Drugs: Implications for Improved Treatment
http://norvect.no/conference/conference-2015/speakers/

Dr Zhang also presented at a recent conference in Cambridge UK, organised by Lyme Disease Action presentations will be available on their website shortly

 http://www.lymediseaseaction.org.uk/   

It was a wonderful opportunity to hear Dr Zhang present and also to have opportunity to discuss his work.

Dr Zhang told me that he studied at Birmingham University and later in London (I think he said UCL) - somewhat ironic for me in view of our Health Authorities head in the sands denial of chronic Lyme Disease, that this leading researcher in this field of why and how Borrelia persists, was trained at two of our Universities.

I have posted previously about Dr Zhang's work 

http://lookingatlyme.blogspot.co.uk/2014/07/fda-approved-drugs-for-persister-cells.html

http://lookingatlyme.blogspot.co.uk/2014/11/zang-on-hunt-for-better-antibiotics-to.html  

http://lookingatlyme.blogspot.co.uk/2015/04/combination-antibiotic-therapy-for-lyme.html

http://lookingatlyme.blogspot.co.uk/2015/06/chronic-lyme-disease-ineffective.html

http://lookingatlyme.blogspot.co.uk/2015/08/persister-mechanisms-in-lyme-disease.html  

DR STEPHEN BARTHOLD LYME DISEASE PERSISTENCE

The above video is once again available at this link http://www.cbc.ca/player/play/2408671744/
Dr Stephen Barthold interview on Lyme disease From CBC Ticked Off The Mystery of Lyme Disease - expert interviews found on the right hand side of this link here

Persistence of Lyme Disease bacteria has been much in the news recently with CDC/NIH Webinar posted earlier here 

The previous post to this on persisters here

Another interesting presentation from Dr Barthold can be found here