Showing posts with label Prof Kim Lewis. Show all posts
Showing posts with label Prof Kim Lewis. Show all posts

Wednesday, 30 March 2016

FIRST LYME DISEASE PULSE-DOSING HUMAN TRIALS WITH MEDICAL SCHOOLS

A new regimen
Lewis and his col­leagues are pro­viding that focus. A sub­pop­u­la­tion of B. burgdor­feri cells, they dis­cov­ered ear­lier, are “per­sister” cells—they are alive but lie dor­mant, in a spore­like state. Because antibi­otics attack only actively func­tioning bac­te­rial cells, per­sis­ters escape the onslaught. How­ever, once the antibi­otic has been flushed from the system, the per­sis­ters “wake up,” says Lewis, dividing and mul­ti­plying until an army of progeny infect the host.
That’s where “pulse dosing” comes in. Lewis’ team, in col­lab­o­ra­tion with researchers studying B. burgdor­feri in mice at Tufts University’s Sackler School of Bio­med­ical Sci­ences, has been ana­lyzing the effect of giving the mice an antibi­otic that kills all the actively func­tioning bac­te­rial cells and then—using the timing that erad­i­cated the pathogen in the test tube—giving addi­tional doses to quash the per­sister cells as they begin to wake up but before they reproduce.
Plans are in the works for the first pulse-​​dosing human trials with med­ical schools.

The above extract is from News at Northeastern go to this link to read the full article:-
 http://www.northeastern.edu/news/2016/03/researchers-investigate-four-promising-new-treatments-for-lyme-disease/
 
'Uni­ver­sity Dis­tin­guished Pro­fessor Kim Lewis, who leads the Lyme dis­ease research team, is now expanding that ther­a­peutic reach with the help of a $1.5 mil­lion grant from the Steven and Alexandra Cohen Foundation.

The team is pur­suing four arms of treatment-​​related research at Northeastern’s Antimi­cro­bial Dis­covery Center, which Lewis directs.

They are: a mouse study of a reg­imen that erad­i­cated the bac­terium in the test tube, set­ting the stage for human trials; antibi­otic cock­tails using existing drugs; strate­gies to dis­cover new drugs that selec­tively target the Lyme bac­terium; and ways to alter the com­po­si­tion of the microbiome—the com­mu­nity of microor­gan­isms inhab­iting the human body—to stop the autoim­mune reac­tions that char­ac­terize the disease.
All four show exciting promise. The grant, Lewis says, “will give us the flex­i­bility to test our approaches in par­allel, which will save us an enor­mous amount of time.”

If Lyme is caught early, patients gen­er­ally recover quickly when treated with antibi­otics, pri­marily doxy­cy­line. How­ever, 10 to 20 per­cent of patients go on to develop a debil­i­tating chronic con­di­tion called Post-​​Treatment Lyme Dis­ease Syn­drome, or PTLDS, with symp­toms that include extreme fatigue, arthritis, muscle pain, and cog­ni­tive difficulties.
I find it amazing that when you show up at the doctor’s office you are not told that there is a 10 to 20 per­cent chance that your life as you know it has ended,” says Lewis. “Nobody seems to be focusing on the next step: How to pre­vent the sub­se­quent rise of the chronic condition.”

Earlier posts on Prof Kim Lewis can be found through this link:-
 http://lookingatlyme.blogspot.co.uk/2015/05/borrelia-burgdorferi-lyme-disease-forms.html

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