Persister mechanisms in Borrelia burgdorferi: implications for improved intervention
Jie Feng, Wanliang Shi, Shuo Zhang and Ying Zhang
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
Subject Category: Antimicrobials and drug resistance
Citation: Emerging Microbes & Infections (2015) 4, e51; doi:10.1038/emi.2015.51
Published online 19 August 2015
Published online 19 August 2015
Received 11 July 2015; Revised 1 August 2015; Accepted 5 August 2015
Go to the link for the full article http://www.nature.com/emi/journal/v4/n8/full/emi201551a.html
Lyme disease caused by Borrelia burgdorferi is the most common vector borne disease in the United States and Europe.1,2 The current treatment for Lyme disease is a 2-4 week antibiotic monotherapy with doxycycline, amoxicillin or cefuroxime.3 While this treatment is effective for the majority of Lyme disease patients, about 10%-20% of patients still have persisting symptoms such as fatigue, muscular pain, and neurological impairment even six months after the treatment,1 a collection of symptoms called Post Treatment Lyme Disease Syndrome (PTLDS).4 While the cause of PTLDS remains unclear and controversial, several hypotheses have been proposed to explain PTLDS, including host response to continued presence of bacterial debris,5 autoimmunity,6 co-infections,7 and presence of bacterial persisters not killed by the current Lyme antibiotics.7Consistent with the persisting organisms not killed by current antibiotics, experiments in various animal models such as mice, dogs and monkeys have shownB. burgdorferi could still be detected after treatment with different Lyme antibiotics though viable organisms could not be cultured.8,9,10 In vitro studies also demonstrated that B. burgdorferi could develop antibiotic tolerant persisters.11 Although persister mechanisms have been reported in the model organism E. coli,12 the mechanisms of B. burgdorferi persisters remain unknown.
Our findings not only shed new light on the mechanisms of B. burgdorferipersisters but also have practical applications. For example, the upregulated genes identified in B. burgdorferi persisters may not only serve as targets for developing new drugs for more effective treatment but also antigens for developing diagnostic tests for persistent Lyme disease, and finally for developing therapeutic vaccines for improved treatment. Future studies are needed to address these possibilities for more effective control of Lyme disease.
Dr Horowitz summed it up:-
Major universities are finally taking an interest in persister bacteria and their role in contributing to chronic symptoms in patients with Lyme disease. Dr Ying Zhang and researchers from Johns Hopkins University just published on Borrelia persisters in Emerging Microbes and Infections where they identified the gene expression profile for Bb persisters that survived antibiotic treatment with doxycycline and amoxicillin. They found differences in transporter genes, bacterial envelope protein coding genes, DNA repair related genes, bacterial chemotaxis genes, bacterial secretion genes, and genes encoding proteases. Comparison of the pathways of the doxycycline persisters and amoxicillin persisters revealed that they share several common features where some genes were up regulated and some down regulated. "These gene expression changes may play important roles in facilitating survival of B. burgdorferi persisters under antibiotic stress...and the upregulated genes identified in B. burgdorferi persisters may not only serve as targets for developing new drugs for more effective treatment but also antigens for developing diagnostic tests for persistent Lyme disease, and finally for developing therapeutic vaccines for improved treatment". The MSIDS map identifies up to 16 different reasons why patients may stay ill after classical treatment for Lyme disease. Persistent infection with borrelia species and co-infections certainly plays a large role in chronic illness, but we must also treat associated inflammation, autoimmune reactions, detoxify internal and external biotoxins, repair the damage caused by free radicals and oxidative stress which damage mitochondria, nerves, brain cells and internal organs, while balancing cytokines, hormones, and the microbiome. Once all of the associated factors on the 16 point MSIDS map have been adequately addressed, the vast majority of my patients improve. A large thanks goes out to the Global Lyme Alliance for their support of this research, and to Dr Zhang and his colleagues at Johns Hopkins for continuing to search for answers for this debilitating illness.