Stationary Phase Persister/Biofilm Microcolony of Borrelia burgdorferi Causes More Severe Disease in a Mouse Model of Lyme Arthritis: Implications for Understanding Persistence, Post-Treatment Lyme Disease Syndrome (PTLDS), and Treatment Failure

http://www.discoverymedicine.com/Jie-Feng/2019/03/persister-biofilm-microcolony-borrelia-burgdorferi-causes-severe-lyme-arthritis-in-mouse-model/

Comment; I like the proposed new way of considering the Lyme disease with new treatment recommendations that appear to be effective; you can’t argue with success!

Author: Jie Feng

Specialty: Microbiology, Infectious Diseases, Immunology
Institution: Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University
Address: Baltimore, Maryland, 21205, United StatesAuthor: Tingting Li

Specialty: Microbiology, Infectious Diseases, Immunology
Institution: Department of Microbiology and Immunology, Tulane University School of Medicine
Address: New Orleans, Louisiana, 70112, United StatesAuthor: Cory Brayton

Specialty: Pathology
Institution: Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine
Address: Baltimore, Maryland, 21205, United StatesAuthor: Harumi Saeki

Abstract: Although most patients with Lyme disease can be cured with a 2-4 week antibiotic therapy, about 10-20% of patients continue to suffer prolonged persistent symptoms, a condition called post-treatment Lyme disease syndrome (PTLDS). The cause for PTLDS is unclear and hotly debated. B. burgdorferi develops morphological variants under stress conditions but their significance is not clear. Here we isolated the biofilm-like microcolony (MC) and planktonic (spirochetal form and round body) (SP) variant forms from the stationary phase culture and showed that the MC and SP were not only more tolerant to the current Lyme antibiotics but also caused more severe arthritis in mice than the log phase spirochete form (LOG). We propose to divide the persistent Lyme disease into two categories: (1) early development of persistent disease from inoculation with persister/biofilm at the beginning of infection introduced by tick bites, or Type I persistent disease (i.e., PTLDS); and (2) late development of persistent disease due to initial infection not being diagnosed or treated in time such that the infection develops into late persistent disease, or Type II persistent disease. Importantly, we show that the murine infection caused by LOG could be eradicated by ceftriaxone whereas the persistent infection established with MC could not be eradicated by doxycycline (Doxy), ceftriaxone (CefT), or vancomycin (Van), or Doxy+CefT or Van+CefT, but could only be eradicated by the persister drug combination daptomycin+doxycycline+ceftriaxone. Our studies demonstrate that varying levels of persistence and pathologies of Borrelia infection can be established with heterogeneous inocula with different morphologies and have different treatment responses. These observations may have broad implications for understanding pathogenesis and treatment of not only persistent Lyme disease but also other persistent infections in general and call for studies to evaluate if treatment of persistent infections with persister drug combination regimens is more effective than the current mostly single-antibiotic monotherapy.

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Dr. Raymond Oenbrink

Dr. Raymond Oenbrink DO is board certified by the American Osteopathic Board of Family Physicians (AOBFP) and the American Board of Addiction Medicine (ABAM). He specializes in complex and chronic illnesses such as Chronic Inflammatory Response Syndrome (CIRS).

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