Point of view on "a selective antibiotic for Lyme disease."
Borrelia burgdorferi, a bacterial spirochete, causes Lyme disease. Doxycycline, amoxicillin, and ceftriaxone are broad-spectrum antibiotics commonly used to treat this tick-borne infection. Unfortunately, these antibiotics can also harm ‘good’ bacteria that comprise the microbiome of our digestive, reproductive, respiratory, and central nervous systems. Damage to this microbiome community of bacteria, bacteriophage, fungi, protozoa and viruses undermines our immune system’s ability to protect us against disease-causing pathogens.
An exciting new finding gives hope that Lyme disease can be treated without harming the microbiome. Dr. Kim Lewis of Northeastern University, a Global Lyme Alliance (GLA)-funded scientist, recently published a study in the prestigious scientific journal Cell. The study describes the re-discovery of an antibiotic called hygromycin A, initially unearthed in 1953 but not of significant clinical utility until now. As a renowned researcher with knowledge and expertise in drug discovery and bacterial antibiotic resistance, Dr. Lewis recognized that soil contains various microorganisms, including spirochetes. These spirochetes must compete against other bacteria for survival and vice versa. With early ‘seed’ funding from GLA and the presumption that soil bacteria could produce an antibiotic effective against spirochetes, his group undertook a comprehensive drug screen. This effort ultimately revealed that hygromycin A, produced by the soil bacterium Streptomyces hygroscopicus, selectively kills B. burgdorferi while sparing the ‘good’ bacteria of the microbiome.
The necessity of achieving this dual goal is evident from the results of another one of Dr. Lewis’ GLA-funded projects. In a human pilot study, it was shown that both B. burgdorferi and conventional antibiotics may foster an unhealthy imbalance of bacteria populating the gut microbiome. This imbalance, reflected in a unique microbiome profile, is particularly evident in patients suffering from post-treatment Lyme disease (PTLD). PTLD is characterized by profound fatigue, pain, and/or cognitive impairment that diminishes a patient’s quality of life. Conventional antibiotics fail to prevent PTLD patients from experiencing symptoms for months or sometimes years after initial infection. This PTLD microbiome profile is associated with a chronic state of inflammation in patients. These discoveries raise hope that the microbiome profile may serve as a point-of-care diagnostic test for PTLD and that hygromycin A may effectively cure this patient population.
This could represent a major treatment advance for those newly infected with B. burgdorferi as well as those suffering from chronic symptoms. As the GLA-funded SLICE studies conducted by Dr. John Aucott (Johns Hopkins University) determined, of the ~476,000 annual cases of Lyme disease in the U.S., roughly 20% may go on to develop PTLD. Additionally, mathematical modeling by Dr. Allison DeLong (GLA Scientific Advisory Board member) and Dr. Mayla Hsu (GLA Director of Research & Science) projected that by the end of last year, as many as 2 million people may be suffering from PTLD.
Coming back to Dr. Lewis’ latest study, it is instructive to appreciate the long and methodical path taken by GLA and its funded investigators to reach this seminal discovery. It began in 2014 when GLA funded Dr. Ying Zhang (then at Johns Hopkins University) to explore the possibility that B. burgdorferi could adopt a dormant form that survives exposure to antibiotics and that these “persister” spirochetes might cause long-hauler symptoms experienced by PTLD patients. Indeed, Dr. Zhang’s group found that B. burgdorferi could form persisters and, unlike live replicating spirochetes, they were unaffected by doxycycline. In follow up studies, Dr. Lewis’ group confirmed Dr. Zhang’s findings that B. burgdorferi could indeed form drug-tolerant persister forms. This stimulated a search for novel or existing FDA-approved drugs, and essential oils and herbal extracts that could kill these persisters. Not only could active botanical medicines kill B. burgdorferi but so too could combinations of conventional drugs such as doxycycline, daptomycin, and cefoperazone.
As intriguing as these findings are, many of the experiments were conducted in test tubes or using mouse models of Lyme disease. This left open the question of relevance to human Lyme disease and whether evidence for persistence of spirochetes can be found in patients. As it turns out, Dr. Monica Embers, a GLA-funded investigator at Tulane University, recently provided provocative and unequivocal proof of the presence of B. burgdorferi in the post-mortem brain tissue of a Lyme disease patient treated with antibiotics, who years later developed chronic neurological symptoms including Lewy body dementia.
Collectively, the vast body of work generated over many years by several GLA-funded investigators has led to one of the first major advancements in decades for the treatment of Lyme disease. Building upon this discovery GLA is proud to partner with Dr. Lewis and Flightpath Biosciences. The latter will usher hygromycin A along the commercialization path, through clinical trials and FDA approval, and ultimately into the hands of physicians struggling to effectively treat patients with PTLD and chronic Lyme disease symptoms. Perhaps most exciting, the use of hygromycin A may prevent tens of thousands of future Lyme patients from developing PTLD or chronic Lyme disease symptoms.
Chief Scientific Officer at Global Lyme Alliance
Timothy J. Sellati, PH.D. is Chief Scientific Officer at Global Lyme Alliance As GLA’s Chief Scientific Officer, Dr. Sellati leads GLA’s research initiatives to accelerate the development of more effective methods of diagnosis and treatment of Lyme and other tick-borne diseases.