Interview with Kim Lewis: Lyme persister cells

Kim Lewis, NorthEastern University, Lyme disease

Dr. Kim Lewis is specialised in persister cells and was mentioned by dr. Horowitz for his current ground breaking research. Could persister cells finally be the explanation why many Lyme symptoms persist after treatment? Dr. Lewis is professor in Microbiology at NorthEastern University in Boston. 

What is your view on ‘chronic’ Lyme?

Lyme Disease is a surprising and neglected disease in the developed world. It should not be neglected, because it affects a large number of people. Even when diagnosed and treated in time, 10-20% of patients develop Post Treatment Lyme Disease Syndrome (PTLDS). We do not understand the nature of PTLDS yet.

What do you research in relationship to Lyme and what might it mean for the clinical practise?

My laboratory focuses on chronic infectious diseases in general. What we found a number of years ago, is that in chronic infection there is a small population of pathogen cells which we call persisters. These cells are dormant, spore-like forms and they become tolerant to antibiotics.

This causes relapsing infections, for example in the urinary tract by E.coli. The same happens with Pseudomonas in the lungs of patients with cystic fibrosis. These persisters also play a role in persisting and relapsing infections with Tuberculosis. This is very well understood thanks to the work from my laboratory and to many other groups around the world. We have been developing treatments against these persister-cells with considerable succes.

An example is the treatment for MRSA, a very nasty infection, which causes both acute and chronic infection such as osteomyelitis and is exceptionally difficult to treat. There we found a compound that is being developed and will hopefully get into clinical use. Based on these successes we decided to attack the very though problem of Lyme disease. We are now researching the link between persisters and PTLDS. There are at least two manifestations of the disease that we could help with.

Post Treatment Lyme Disease Syndrome

The first is prevention of PTLDS. Now 10-15% of patients, who where diagnosed and treated timely, will go on and develop PTLDS. Everybody who I spoke with, including doctors who are very sceptical about the presence of the pathogen in people with PTLDS, agree that the shorter the time this pathogen contacts the body the lower the probability there will be any unpleasant consequences.

So using a very strong and aggressive therapy that almost immediately wipes out the pathogen instead of a therapy that takes 2-3 weeks the chances that you will go on to develop PTLDS will probably dramatically diminish. The reason we need this 2-3 week treatments are I strongly suspect are due to the reason of these persisters. Antibiotics should be working in a day or two instead of several weeks.

So we aim to develop therapeutics that will be considerably more effective than the standard doxycycline treatment and prevent this completely unacceptable 10-15% failure rate.

Lyme artritis

The second area is where people are properly diagnosed, but not treated in a timely manner and who have developed Lyme artritis. Lyme artritis often takes 3 months of antibiotics to eradicate. This is not a proper way to treat an infectious disease.

We should not be treating patients for 3 months with antibiotics that have enormous side-effects, wipe out the microbiome and do all kinds of nasty things. We should do considerably better than that. There is little doubt that it is because there are dormant persister-cells. So this is where I see obvious ways to intervene.

Then there is the complex story of people like yourself, who unfortunately suffer from PTLDS. One possibility is that there are still remaining persisters in low numbers that cause a low grade inflammation which presents as an auto-immune disease. Another possibility, which the majority of doctors seem to favour, is that the pathogen is gone and there has been irreversible wreckage done to the immune system. In both cases you have presentation of symptoms.

One thing we would like to avoid is to be unsuccessful in whatever we approach. I don’t like to work on projects, where there isn’t the distinct possibility that we are going to win. So obviously I was thinking about this problem and what is it that we should to do to satisfy ourselves that the pathogen is gone from patients with PTLDS.

There have been very interesting studies on auto-immune diseases that if you can intervene by restoring the microbiome, symptoms improve. Currently we are working with the group from John Hopkins University by looking into the microbiome of patients with PTLDS. We are examining if there are any abnormalities. If there are, we have a pretty good idea of how to fix that. So these are my general thoughts of how we can interfere with the disease.

How do you differentiate between persistent infection and PTLDS?

I’m not an expert in diagnostics, but of course I’ve followed this because, to be able to work properly, we need to be sure that someone has PTLDS and not another condition. It would be nice if we found a biological marker. For example, we could take a blood test and say, this patient has PTLDS.

Until recently there was nothing in that direction. I recently attended a Lyme meeting and the Columbia University group presented very exciting results. They have discovered markers that can identify PTLDS with about 80% accuracy. That is quite high. They have not published this yet, but it’s on the way and I think this will make a big difference.

Is culture for Borrelia species the golden standard?

Several groups reported in an animal model that you could detect the DNA after treatment of the animal for the Borrelia. The DNA is there but you cannot culture the pathogen. You could also put a tick on that animal and then that tick will pick up the pathogen and transmit it to another animal that will show the same DNA.

That is the unculturable form of Lyme disease. We are working with that right now. One of the things my laboratory has experience with is unculturable bacteria. We will get to the bottom of it.

Some doctors say co-infections are involved what do you think?

There will be many factors of probability for the patient to develop PTLDS. At John Hopkins University they have about 10% of patients that will go on and develop PTLDS. Of course they run routinely tests for co-infections and so far these numbers are not huge. I don’t see that it is only those patients that are infected with more than Borrelia Burgdoferi will go on and develop PTLDS and those that where only infected with Borrelia Burgdoferi will not develop it. We don’t see that kind of correlation.

For patients with ongoing symptoms, is there hope?

In America there has been a renewed and/or new interest in Lyme disease. From a variety of fields apart from infectious disease such as immunology, diagnostics, epidemiology and metabolomics are joining this field. There is a network of collaborations and that was just not the case 10 years ago. There are still holes in the research which we are going to fill rapidly.

Is there anything you would like to add that I didn’t ask?

One of the reasons this field has been neglected is because funds for scientists to do meaningful research where not available. Either in America or in Europe. That has been changing in America. A number of foundations have been providing considerable and generous support for scientists like myself. NIH is also stepping up. The department of Defence in America has opened up a program.

I don’t think that a comprehensible thing is happening in Europe. The European manifestation of disease is somewhat different than in America. While we hope that whatever we will find here will translate that is not a given. It would be nice to see similar and well funded efforts happening in Europe.

“I hope that people like yourself will help the governments and foundations to get their act together and properly fund work on this disease.”