Borreliella burgdorferi Antimicrobial-Tolerant Persistence in Lyme Disease and Posttreatment Lyme Disease Syndromes
ABSTRACT The annual incidence of Lyme disease, caused by tick-transmitted Borreliella burgdorferi, is estimated to be at least 476,000 cases in the United States and many more worldwide. Ten to 20% of antimicrobial-treated Lyme disease patients display posttreatment Lyme disease syndrome (PTLDS), a...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2022-06-01
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| Series: | mBio |
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| Online Access: | https://journals.asm.org/doi/10.1128/mbio.03440-21 |
| _version_ | 1818249263206891520 |
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| author | Felipe C. Cabello Monica E. Embers Stuart A. Newman Henry P. Godfrey |
| author_facet | Felipe C. Cabello Monica E. Embers Stuart A. Newman Henry P. Godfrey |
| author_sort | Felipe C. Cabello |
| collection | DOAJ |
| description | ABSTRACT The annual incidence of Lyme disease, caused by tick-transmitted Borreliella burgdorferi, is estimated to be at least 476,000 cases in the United States and many more worldwide. Ten to 20% of antimicrobial-treated Lyme disease patients display posttreatment Lyme disease syndrome (PTLDS), a clinical complication whose etiology and pathogenesis remain uncertain. Autoimmunity, cross-reactivity, molecular mimicry, coinfections, and borrelial tolerance to antimicrobials/persistence have been hypothesized and studied as potential causes of PTLDS. Studies of borrelial tolerance/persistence in vitro in response to antimicrobials and experimental studies in mice and nonhuman primates, taken together with clinical reports, have revealed that B. burgdorferi becomes tolerant to antimicrobials and may sometimes persist in animals and humans after the currently recommended antimicrobial treatment. Moreover, B. burgdorferi is pleomorphic and can generate viable-but-nonculturable bacteria, states also involved in antimicrobial tolerance. The multiple regulatory pathways and structural genes involved in mediating this tolerance to antimicrobials and environmental stressors by persistence might include the stringent (rel and dksA) and host adaptation (rpoS) responses, sugar metabolism (glpD), and polypeptide transporters (opp). Application of this recently reported knowledge to clinical studies can be expected to clarify the potential role of bacterial antibacterial tolerance/persistence in Lyme disease and PTLDS. |
| first_indexed | 2024-12-12T15:33:43Z |
| format | Article |
| id | doaj.art-d92950ef88644013be912c1cc5b960e2 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-12T15:33:43Z |
| publishDate | 2022-06-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-d92950ef88644013be912c1cc5b960e22022-12-22T00:20:03ZengAmerican Society for MicrobiologymBio2150-75112022-06-0113310.1128/mbio.03440-21Borreliella burgdorferi Antimicrobial-Tolerant Persistence in Lyme Disease and Posttreatment Lyme Disease SyndromesFelipe C. Cabello0Monica E. Embers1Stuart A. Newman2Henry P. Godfrey3Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, New York, USADivision of Immunology, Tulane National Primate Research Center, Tulane University Health Sciences, Covington, Louisiana, USADepartment of Cell Biology and Anatomy, New York Medical College, Valhalla, New York, USADepartment of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, New York, USAABSTRACT The annual incidence of Lyme disease, caused by tick-transmitted Borreliella burgdorferi, is estimated to be at least 476,000 cases in the United States and many more worldwide. Ten to 20% of antimicrobial-treated Lyme disease patients display posttreatment Lyme disease syndrome (PTLDS), a clinical complication whose etiology and pathogenesis remain uncertain. Autoimmunity, cross-reactivity, molecular mimicry, coinfections, and borrelial tolerance to antimicrobials/persistence have been hypothesized and studied as potential causes of PTLDS. Studies of borrelial tolerance/persistence in vitro in response to antimicrobials and experimental studies in mice and nonhuman primates, taken together with clinical reports, have revealed that B. burgdorferi becomes tolerant to antimicrobials and may sometimes persist in animals and humans after the currently recommended antimicrobial treatment. Moreover, B. burgdorferi is pleomorphic and can generate viable-but-nonculturable bacteria, states also involved in antimicrobial tolerance. The multiple regulatory pathways and structural genes involved in mediating this tolerance to antimicrobials and environmental stressors by persistence might include the stringent (rel and dksA) and host adaptation (rpoS) responses, sugar metabolism (glpD), and polypeptide transporters (opp). Application of this recently reported knowledge to clinical studies can be expected to clarify the potential role of bacterial antibacterial tolerance/persistence in Lyme disease and PTLDS.https://journals.asm.org/doi/10.1128/mbio.03440-21bacterial persistenceBorrelia burgdorferiLyme diseasepost-Lyme disease syndromesantimicrobial tolerancepersistence |
| spellingShingle | Felipe C. Cabello Monica E. Embers Stuart A. Newman Henry P. Godfrey Borreliella burgdorferi Antimicrobial-Tolerant Persistence in Lyme Disease and Posttreatment Lyme Disease Syndromes mBio bacterial persistence Borrelia burgdorferi Lyme disease post-Lyme disease syndromes antimicrobial tolerance persistence |
| title | Borreliella burgdorferi Antimicrobial-Tolerant Persistence in Lyme Disease and Posttreatment Lyme Disease Syndromes |
| title_full | Borreliella burgdorferi Antimicrobial-Tolerant Persistence in Lyme Disease and Posttreatment Lyme Disease Syndromes |
| title_fullStr | Borreliella burgdorferi Antimicrobial-Tolerant Persistence in Lyme Disease and Posttreatment Lyme Disease Syndromes |
| title_full_unstemmed | Borreliella burgdorferi Antimicrobial-Tolerant Persistence in Lyme Disease and Posttreatment Lyme Disease Syndromes |
| title_short | Borreliella burgdorferi Antimicrobial-Tolerant Persistence in Lyme Disease and Posttreatment Lyme Disease Syndromes |
| title_sort | borreliella burgdorferi antimicrobial tolerant persistence in lyme disease and posttreatment lyme disease syndromes |
| topic | bacterial persistence Borrelia burgdorferi Lyme disease post-Lyme disease syndromes antimicrobial tolerance persistence |
| url | https://journals.asm.org/doi/10.1128/mbio.03440-21 |
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