期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 115, 期 16, 页码 E3788-E3797出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1718595115
关键词
Borrelia burgdorferi; Lyme disease; immune evasion; microbial persistence; antimicrobial peptide
资金
- National Institute of Allergy and Infectious Diseases (NIAID) [AI080615, AI116620, AI128232]
- Center for Cancer Research, National Cancer Institute
- NIAID
- Spanish Ministry of Economy and Competitiveness [SAF2015-65327]
- Deborah and Mark Blackman Postdoctoral Fellowship from Global Lyme Alliance
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR001114, TL1TR001113] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL083464, U01HL126497, R01HL134043] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI080615, R03AI128232, R01AI116620, ZIAAI000695] Funding Source: NIH RePORTER
Borrelia burgdorferi is one of the few extracellular pathogens capable of establishing persistent infection in mammals. The mechanisms that sustain long-term survival of this bacterium are largely unknown. Here we report a unique innate immune evasion strategy of B. burgdorferi, orchestrated by a surface protein annotated as BBA57, through its modulation of multiple spirochete virulent determinants. BBA57 function is critical for early infection but largely redundant for later stages of spirochetal persistence, either in mammals or in ticks. The protein influences host IFN responses as well as suppresses multiple host microbicidal activities involving serum complement, neutrophils, and antimicrobial peptides. We also discovered a remarkable plasticity in BBA57-mediated spirochete immune evasion strategy because its loss, although resulting in near clearance of pathogens at the inoculum site, triggers nonheritable adaptive changes that exclude detectable nucleotide alterations in the genome but incorporate transcriptional reprograming events. Understanding the malleability in spirochetal immune evasion mechanisms that ensures their host persistence is critical for the development of novel therapeutic and preventive approaches to combat long-term infections like Lyme borreliosis.
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