Dual roles for a tick protein disulfide isomerase during the life cycle of the Lyme disease agent
ABSTRACT The protein disulfide isomerase (PDI) family is a group of enzymes that have thiol-disulfide oxidoreductase, disulfide isomerase, and redox-dependent chaperone activities. PDIs facilitate diverse infections in mammalian hosts by directly binding to pathogens, immunomodulation, or enabling m...
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| Language: | English |
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American Society for Microbiology
2024-12-01
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| Series: | mBio |
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| Online Access: | https://journals.asm.org/doi/10.1128/mbio.01754-24 |
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| author | Xiaotian Tang Yingjun Cui Ushuu Namarra Xiuqi Tian Freddie Rivas-Giorgi Erol Fikrig |
| author_facet | Xiaotian Tang Yingjun Cui Ushuu Namarra Xiuqi Tian Freddie Rivas-Giorgi Erol Fikrig |
| author_sort | Xiaotian Tang |
| collection | DOAJ |
| description | ABSTRACT The protein disulfide isomerase (PDI) family is a group of enzymes that have thiol-disulfide oxidoreductase, disulfide isomerase, and redox-dependent chaperone activities. PDIs facilitate diverse infections in mammalian hosts by directly binding to pathogens, immunomodulation, or enabling microbial invasion of host cells. PDI homologs within pathogens are also potential virulence factors. However, whether PDIs within blood-feeding ticks influence microbial infection remains unknown. In this study, we investigated the role of Ixodes scapularis PDIs, on the Lyme disease agent, Borrelia burgdorferi. I. scapularis has five PDIs (IsPDIs), and IsPDIA6 gene expression is reduced upon B. burgdorferi infection in the tick. IsPDIA6-mediated trypsin inhibitor gene expression contributes to B. burgdorferi colonization within the tick midgut. IsPDIA6 is also secreted into the host during tick feeding, alters cytokine/chemokine expression at the tick bite site, and influences the initial stage of bacterial infection in mice. These data demonstrate that a PDI from a blood-feeding vector plays a role in the life cycle of an extracellular pathogen.IMPORTANCEVector-borne diseases are a leading cause of death and illness worldwide, and more than 80% of the global population live in areas at risk from at least one major vector-borne disease. In this study, we demonstrate a dual role of a specific Ixodes tick protein disulfide isomerase (PDI) in inhibiting the ability of the Lyme disease agent to colonize ticks and also in enhancing the initial stage of spirochete infection of mice. This study represents a novel conceptual advancement that a PDI from a blood-feeding vector plays important roles in the life cycle of an extracellular pathogen. |
| format | Article |
| id | doaj-art-069be8bc3d4d43b9bbec2ca974b2f7ce |
| institution | DOAJ |
| issn | 2150-7511 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj-art-069be8bc3d4d43b9bbec2ca974b2f7ce2025-08-20T02:50:04ZengAmerican Society for MicrobiologymBio2150-75112024-12-01151210.1128/mbio.01754-24Dual roles for a tick protein disulfide isomerase during the life cycle of the Lyme disease agentXiaotian Tang0Yingjun Cui1Ushuu Namarra2Xiuqi Tian3Freddie Rivas-Giorgi4Erol Fikrig5Zhejiang Key Laboratory of Biology and Ecological Regulation of Crop Pathogens and Insects, Institute of Insect Sciences, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou, ChinaSection of Infectious Diseases, Department of Internal Medicine, School of Medicine, Yale University, New Haven, Connecticut, USAHistory of Science, Medicine, and Public Health Program, Yale College, New Haven, Connecticut, USASection of Infectious Diseases, Department of Internal Medicine, School of Medicine, Yale University, New Haven, Connecticut, USAMolecular Biochemistry and Biophysics Program, Yale College, New Haven, Connecticut, USASection of Infectious Diseases, Department of Internal Medicine, School of Medicine, Yale University, New Haven, Connecticut, USAABSTRACT The protein disulfide isomerase (PDI) family is a group of enzymes that have thiol-disulfide oxidoreductase, disulfide isomerase, and redox-dependent chaperone activities. PDIs facilitate diverse infections in mammalian hosts by directly binding to pathogens, immunomodulation, or enabling microbial invasion of host cells. PDI homologs within pathogens are also potential virulence factors. However, whether PDIs within blood-feeding ticks influence microbial infection remains unknown. In this study, we investigated the role of Ixodes scapularis PDIs, on the Lyme disease agent, Borrelia burgdorferi. I. scapularis has five PDIs (IsPDIs), and IsPDIA6 gene expression is reduced upon B. burgdorferi infection in the tick. IsPDIA6-mediated trypsin inhibitor gene expression contributes to B. burgdorferi colonization within the tick midgut. IsPDIA6 is also secreted into the host during tick feeding, alters cytokine/chemokine expression at the tick bite site, and influences the initial stage of bacterial infection in mice. These data demonstrate that a PDI from a blood-feeding vector plays a role in the life cycle of an extracellular pathogen.IMPORTANCEVector-borne diseases are a leading cause of death and illness worldwide, and more than 80% of the global population live in areas at risk from at least one major vector-borne disease. In this study, we demonstrate a dual role of a specific Ixodes tick protein disulfide isomerase (PDI) in inhibiting the ability of the Lyme disease agent to colonize ticks and also in enhancing the initial stage of spirochete infection of mice. This study represents a novel conceptual advancement that a PDI from a blood-feeding vector plays important roles in the life cycle of an extracellular pathogen.https://journals.asm.org/doi/10.1128/mbio.01754-24protein disulfide isomeraseIxodes scapularisLyme diseaseBorrelia burgdorferiinfectiontick |
| spellingShingle | Xiaotian Tang Yingjun Cui Ushuu Namarra Xiuqi Tian Freddie Rivas-Giorgi Erol Fikrig Dual roles for a tick protein disulfide isomerase during the life cycle of the Lyme disease agent mBio protein disulfide isomerase Ixodes scapularis Lyme disease Borrelia burgdorferi infection tick |
| title | Dual roles for a tick protein disulfide isomerase during the life cycle of the Lyme disease agent |
| title_full | Dual roles for a tick protein disulfide isomerase during the life cycle of the Lyme disease agent |
| title_fullStr | Dual roles for a tick protein disulfide isomerase during the life cycle of the Lyme disease agent |
| title_full_unstemmed | Dual roles for a tick protein disulfide isomerase during the life cycle of the Lyme disease agent |
| title_short | Dual roles for a tick protein disulfide isomerase during the life cycle of the Lyme disease agent |
| title_sort | dual roles for a tick protein disulfide isomerase during the life cycle of the lyme disease agent |
| topic | protein disulfide isomerase Ixodes scapularis Lyme disease Borrelia burgdorferi infection tick |
| url | https://journals.asm.org/doi/10.1128/mbio.01754-24 |
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