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A selective antibiotic for Lyme disease.

ABSTRACT: Lyme disease is on the rise. Caused by a spirochete Borreliella burgdorferi, it affects an estimated 500,000 people in the United States alone. The antibiotics currently used to treat Lyme disease are broad spectrum, damage the microbiome, and select for resistance in non-target bacteria. We therefore sought to identify a compound acting selectively against B. burgdorferi. A screen of soil micro-organisms revealed a compound highly selective against spirochetes, including B. burgdorferi. Unexpectedly, this compound was determined to be hygromycin A, a known antimicrobial produced by Streptomyces hygroscopicus. Hygromycin A targets the ribosomes and is taken up by B. burgdorferi, explaining its selectivity. Hygromycin A cleared the B. burgdorferi infection in mice, including animals that ingested the compound in a bait, and was less disruptive to the fecal microbiome than clinically relevant antibiotics. This selective antibiotic holds the promise of providing a better therapeutic for Lyme disease and eradicating it in the environment.

SUBMITTER: Leimer N

PROVIDER: S-EPMC8526400 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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A selective antibiotic for Lyme disease.

Leimer Nadja N Wu Xiaoqian X Imai Yu Y Morrissette Madeleine M Pitt Norman N Favre-Godal Quentin Q Iinishi Akira A Jain Samta S Caboni Mariaelena M Leus Inga V IV Bonifay Vincent V Niles Samantha S Bargabos Rachel R Ghiglieri Meghan M Corsetti Rachel R Krumpoch Megan M Fox Gabriel G Son Sangkeun S Klepacki Dorota D Polikanov Yury S YS Freliech Cecily A CA McCarthy Julie E JE Edmondson Diane G DG Norris Steven J SJ D'Onofrio Anthony A Hu Linden T LT Zgurskaya Helen I HI Lewis Kim K

Cell 20211006 21

Lyme disease is on the rise. Caused by a spirochete Borreliella burgdorferi, it affects an estimated 500,000 people in the United States alone. The antibiotics currently used to treat Lyme disease are broad spectrum, damage the microbiome, and select for resistance in non-target bacteria. We therefore sought to identify a compound acting selectively against B. burgdorferi. A screen of soil micro-organisms revealed a compound highly selective against spirochetes, including B. burgdorferi. Unexpec ...[more]

PMID: 34619078

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Project description:BACKGROUND: We have shown previously that extended intravenous antibiotic therapy is associated with low morbidity and no mortality in patients referred for treatment of neurologic Lyme disease. In this study, we evaluated the benefit of extended intravenous antibiotic therapy in patients with symptoms of neurologic Lyme disease. METHODS: Patients with significant neurologic symptoms and positive testing for Borrelia burgdorferi were treated with intravenous antibiotics, and biweekly evaluation of symptom severity was performed using a six-level ordinal scale. Four symptoms were selected a priori as primary outcome measures in the study, ie, fatigue, cognition, myalgias, and arthralgias. Patients were placed into five groups according to time on treatment (1-4, 5-8, 9-12, 13-24, and 25-52 weeks), and changes in the primary symptoms as a function of time on treatment were analyzed using a mixed-effects proportional odds model. RESULTS: Among 158 patients with more than one follow-up visit who were monitored for up to 1 year, there were on average 6.7 visits per person (median 5, range 2-24). The last follow-up day was on average 96 days after enrollment (median 69, range 7-354 days), corresponding to the length of antibiotic therapy. Each primary symptom was significantly improved at one or more time points during the study. For cognition, fatigue, and myalgias, the greatest improvement occurred in patients on the longest courses of treatment (25-52 weeks) with odds ratios (OR) for improvement of 1.97 (P = 0.02), 2.22 (P < 0.01), and 2.08 (P = 0.01), respectively. In contrast, arthralgias were only significantly improved during the initial 1-4 weeks of therapy (OR: 1.57, P = 0.04), and the beneficial effect of longer treatment did not reach statistical significance for this symptom. CONCLUSION: Prolonged intravenous antibiotic therapy is associated with improved cognition, fatigue, and myalgias in patients referred for treatment of neurologic Lyme disease. Treatment for 25-52 weeks may be necessary to obtain symptomatic improvement in these patients.

Project description:It has long been observed in clinical practice that a subset of patients with Lyme disease report a constellation of symptoms such as fatigue, cognitive difficulties, and musculoskeletal pain, which may last for a significant period of time. These symptoms, which can range from mild to severe, have been reported throughout the literature in both prospective and population-based studies in Lyme disease endemic regions. The etiology of these symptoms is unknown, however several illness-causing mechanisms have been hypothesized, including microbial persistence, host immune dysregulation through inflammatory or secondary autoimmune pathways, or altered neural networks, as in central sensitization. Evaluation and characterization of persistent symptoms in Lyme disease is complicated by potential independent, repeat exposures to B. burgdorferi, as well as the potential for co-morbid diseases with overlapping symptom profiles. Antibody testing for B. burgdorferi is an insensitive measure after treatment, and no other FDA-approved tests currently exist. As such, diagnosis presents a complex challenge for physicians, while the lived experience for patients is one marked by uncertainty and often illness invalidation. Currently, there are no FDA-approved pharmaceutical therapies, and the safety and efficacy of off-label and/or complementary therapies have not been well studied and are not agreed-upon within the medical community. Post-treatment Lyme disease represents a narrow, defined, mechanistically-neutral subset of this larger, more heterogeneous group of patients, and is a useful definition in research settings as an initial subgroup of study. The aim of this paper is to review the current literature on the diagnosis, etiology, risk factors, and treatment of patients with persistent symptoms in the context of Lyme disease. The meaning and relevance of existing patient subgroups will be discussed, as will future research priorities, including the need to develop illness biomarkers, elucidate the biologic mechanisms of disease, and drive improvements in therapeutic options.

Dataset Information

A selective antibiotic for Lyme disease.

Publications

A selective antibiotic for Lyme disease.

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