from Huffington Post, November 2, 2017
by Mary Beth Pfeiffer
Investigative journalist Mary Beth Pfeiffer speaks with GLA research grantees Dr. Monica Embers, Dr. Ying Zhang, Dr. Brian Fallon and Dr. Kim Lewis about Lyme disease persistence.
The words “sleeper cell” may not conjure thoughts of the bacterium that causes Lyme disease. But for thousands of people worldwide, this powerful single cell is as destructive as a covert terror group – and far more common.
The “sleeper cell” term was used in a recent science journal article that described the considerable ability of the Lyme disease pathogen to change shapes, develop protective films, and otherwise survive assault by antibiotics, only to strike again when least expected. The organism, which infects more than 300,000 Americans annually and some 200,000 in western Europe, has repeatedly demonstrated “tolerance to otherwise lethal doses of antimicrobials,” the article said.
Lyme disease is one of the most controversial diagnoses in medicine, with debate centering on why some 10 to 20 percent of patients remain ill after treatment. In offering a possible explanation for that, the sleeper cell article, published last month in Environmental Microbiology journal, challenges mainstream contentions that the infection is almost always eliminated by short courses of antibiotics. Lyme patient advocates see the article as a potential watershed moment in Lyme thought. Here’s why:
- First, as a review of the scientific literature, the article contextualizes and pays tribute to a growing body of research demonstrating that some Lyme pathogens, called “persisters,” survive antibiotic onslaught in test-tube and animal experiments. Such research, which has fought for recognition amid criticism from established researchers, could upend prevailing treatment dogma, which holds that common antimicrobials readily kill the pathogen.
- As significant, the article’s authors — experts in microbiology, pathology, and cell biology – come from New York Medical College, which is also home to leading physician-researchers who wrote the prevailing guidelines of Lyme diagnosis and treatment. The article, and the research it supports, unquestionably challenges that model, which dictates Lyme disease care in the United States and many other countries and has been used to discipline doctors who practice outside them.
In lab tests, the Lyme pathogen has repeatedly demonstrated ‘tolerance to otherwise lethal doses of antimicrobials.’ — From ‘Sleeper cells: the stringent response and persistence in the Borreliella (Borrelia) burgdorferi enzootic cycle.’
The authors of the sleeper cell article, led by Felipe Cabello in the college’s Department of Microbiology and Immunology, had reported in 2002 and 2005 on the ability of the Lyme pathogen, called Borrelia burgdorferi, to activate or turn off selected genes, thereby speeding or slowing its growth or altering basic functions of reproduction and metabolism. These changes are called the “stringent response” and are thought to allow Borrelia to survive under conditions of nutritional and environmental stress in everything from the bellies of ticks to the bloodstreams of mammals.
Key to lingering infection?
The stringent response, the group’s new article hypothesizes, may also be what allows the Lyme pathogen to survive standard doses of medicine’s best antibiotics. Among the article’s nearly 200 citations is the work, since 2014, of scientists from Johns Hopkins, Northeastern and Tulane universities who have shown that doxycycline, amoxicillin and other common Lyme disease drugs leave behind persister cells. Those researchers sometimes tried dozens of antibiotics, in combination or in repeated rounds called pulsing, and still had difficulty eradicating the pathogen in test tubes.
Persistence after treatment is shared by other bacteria; penicillin was found in 1942 to leave behind 1 percent of streptococcal cells. But the phenomenon in B. burgdorferi, the bacterium that causes Lyme disease, is seen as a potential explanation for lingering symptoms of some 30,000 to 60,000 Americans annually. Treated Lyme pathogens, for one, produce more persisters, for example, than treated E. coli.
Brian Fallon, director of the Lyme & Tick-borne Diseases Research Center at Columbia University Medical Center and author of a new book, “Conquering Lyme Disease,” said the article and the considerable research it summarizes “should give hope to patients.”
“These investigations demonstrate that an increasing number of scientists not only regard Borrelia persistence to be an indisputable fact that is essential to its biology,” he wrote in an email, “but also that the persistence of these organisms may be playing an important role in persistent symptoms that plague some patients despite standard antibiotic therapy.”
Since the late 1990s, laboratory experiments have found evidence of ongoing post-treatment infection in dogs, mice, and, in particular, monkeys, from which Tulane University researchers recovered intact Lyme spirochetes. In a mouse study at the University of California, Davis, similarly, the infection resurged a year after treatment, although the spirochetes could not be cultured.