Ehrlichia effector TRP120 manipulates bacteremia to facilitate tick acquisition
ABSTRACTEhrlichia species are obligatory intracellular bacteria that cause a potentially fatal disease, human ehrlichiosis. The biomolecular mechanisms of tick acquisition of Ehrlichia and transmission between ticks and mammals are poorly understood. Ehrlichia japonica infection of mice recapitulate...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2024-04-01
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| Series: | mBio |
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| Online Access: | https://journals.asm.org/doi/10.1128/mbio.00476-24 |
| _version_ | 1797215268925079552 |
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| author | Tsian Zhang Rory C. Chien Khemraj Budachetri Mingqun Lin Prosper Boyaka Weiyan Huang Yasuko Rikihisa |
| author_facet | Tsian Zhang Rory C. Chien Khemraj Budachetri Mingqun Lin Prosper Boyaka Weiyan Huang Yasuko Rikihisa |
| author_sort | Tsian Zhang |
| collection | DOAJ |
| description | ABSTRACTEhrlichia species are obligatory intracellular bacteria that cause a potentially fatal disease, human ehrlichiosis. The biomolecular mechanisms of tick acquisition of Ehrlichia and transmission between ticks and mammals are poorly understood. Ehrlichia japonica infection of mice recapitulates the full spectrum of human ehrlichiosis. We compared the pathogenicity and host acquisition of wild-type E. japonica with an isogenic transposon mutant of E. japonica that lacks tandem repeat protein 120 (TRP120) (ΔTRP120). Both wild-type and ΔTRP120 E. japonica proliferated similarly in cultures of mammalian and tick cells. Upon inoculation into mice, both wild-type and ΔTRP120 E. japonica multiplied to high levels in various tissues, with similar clinical chemistry and hematologic changes, proinflammatory cytokine induction, and fatal disease. However, the blood levels of ΔTRP120 E. japonica were almost undetectable within 24 h, whereas the levels of the wild type increased exponentially. Greater than 90% of TRP120 was released from infected cells into the culture medium. Mouse blood monocytes exposed to native TRP120 from culture supernatants showed significantly reduced cell surface expression of the transmigration-related markers Ly6C and CD11b. Larval ticks attached to mice infected with either wild-type or ΔTRP120 E. japonica imbibed similar amounts of blood and subsequently molted to nymphs at similar rates. However, unlike wild-type E. japonica, the ΔTRP120 mutant was minimally acquired by larval ticks and subsequent molted nymphs and, thus, failed to transmit to naïve mice. Thus, TRP120 is required for bacteremia but not disease. These findings suggest a novel mechanism whereby an obligatory intracellular bacterium manipulates infected blood monocytes to sustain the tick–mammal transmission cycle.IMPORTANCEEffective prevention of tick-borne diseases such as human ehrlichiosis requires an understanding of how disease-causing organisms are acquired. Ehrlichia species are intracellular bacteria that require infection of both mammals and ticks, involving cycles of transmission between them. Mouse models of ehrlichiosis and tick–mouse transmission can advance our fundamental understanding of the pathogenesis and prevention of ehrlichiosis. Herein, a mutant of Ehrlichia japonica was used to investigate the role of a single Ehrlichia factor, named tandem repeat protein 120 (TRP120), in infection of mammalian and tick cells in culture, infection and disease progression in mice, and tick acquisition of E. japonica from infected mice. Our results suggest that TRP120 is necessary only for Ehrlichia proliferation in circulating mouse blood and ongoing bacteremia to permit Ehrlichia acquisition by ticks. This study provides new insights into the importance of bacterial factors in regulating bacteremia, which may facilitate tick acquisition of pathogens. |
| first_indexed | 2024-04-24T11:27:23Z |
| format | Article |
| id | doaj.art-0b813c573df945928c97a7af690bb59b |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-04-24T11:27:23Z |
| publishDate | 2024-04-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-0b813c573df945928c97a7af690bb59b2024-04-10T13:01:15ZengAmerican Society for MicrobiologymBio2150-75112024-04-0115410.1128/mbio.00476-24Ehrlichia effector TRP120 manipulates bacteremia to facilitate tick acquisitionTsian Zhang0Rory C. Chien1Khemraj Budachetri2Mingqun Lin3Prosper Boyaka4Weiyan Huang5Yasuko Rikihisa6Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USADepartment of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USADepartment of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USADepartment of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USADepartment of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USADepartment of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USADepartment of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USAABSTRACTEhrlichia species are obligatory intracellular bacteria that cause a potentially fatal disease, human ehrlichiosis. The biomolecular mechanisms of tick acquisition of Ehrlichia and transmission between ticks and mammals are poorly understood. Ehrlichia japonica infection of mice recapitulates the full spectrum of human ehrlichiosis. We compared the pathogenicity and host acquisition of wild-type E. japonica with an isogenic transposon mutant of E. japonica that lacks tandem repeat protein 120 (TRP120) (ΔTRP120). Both wild-type and ΔTRP120 E. japonica proliferated similarly in cultures of mammalian and tick cells. Upon inoculation into mice, both wild-type and ΔTRP120 E. japonica multiplied to high levels in various tissues, with similar clinical chemistry and hematologic changes, proinflammatory cytokine induction, and fatal disease. However, the blood levels of ΔTRP120 E. japonica were almost undetectable within 24 h, whereas the levels of the wild type increased exponentially. Greater than 90% of TRP120 was released from infected cells into the culture medium. Mouse blood monocytes exposed to native TRP120 from culture supernatants showed significantly reduced cell surface expression of the transmigration-related markers Ly6C and CD11b. Larval ticks attached to mice infected with either wild-type or ΔTRP120 E. japonica imbibed similar amounts of blood and subsequently molted to nymphs at similar rates. However, unlike wild-type E. japonica, the ΔTRP120 mutant was minimally acquired by larval ticks and subsequent molted nymphs and, thus, failed to transmit to naïve mice. Thus, TRP120 is required for bacteremia but not disease. These findings suggest a novel mechanism whereby an obligatory intracellular bacterium manipulates infected blood monocytes to sustain the tick–mammal transmission cycle.IMPORTANCEEffective prevention of tick-borne diseases such as human ehrlichiosis requires an understanding of how disease-causing organisms are acquired. Ehrlichia species are intracellular bacteria that require infection of both mammals and ticks, involving cycles of transmission between them. Mouse models of ehrlichiosis and tick–mouse transmission can advance our fundamental understanding of the pathogenesis and prevention of ehrlichiosis. Herein, a mutant of Ehrlichia japonica was used to investigate the role of a single Ehrlichia factor, named tandem repeat protein 120 (TRP120), in infection of mammalian and tick cells in culture, infection and disease progression in mice, and tick acquisition of E. japonica from infected mice. Our results suggest that TRP120 is necessary only for Ehrlichia proliferation in circulating mouse blood and ongoing bacteremia to permit Ehrlichia acquisition by ticks. This study provides new insights into the importance of bacterial factors in regulating bacteremia, which may facilitate tick acquisition of pathogens.https://journals.asm.org/doi/10.1128/mbio.00476-24Ehrlichia japonicaTRP120bacteremiatick acquisition/transmissionbloodmouse |
| spellingShingle | Tsian Zhang Rory C. Chien Khemraj Budachetri Mingqun Lin Prosper Boyaka Weiyan Huang Yasuko Rikihisa Ehrlichia effector TRP120 manipulates bacteremia to facilitate tick acquisition mBio Ehrlichia japonica TRP120 bacteremia tick acquisition/transmission blood mouse |
| title | Ehrlichia effector TRP120 manipulates bacteremia to facilitate tick acquisition |
| title_full | Ehrlichia effector TRP120 manipulates bacteremia to facilitate tick acquisition |
| title_fullStr | Ehrlichia effector TRP120 manipulates bacteremia to facilitate tick acquisition |
| title_full_unstemmed | Ehrlichia effector TRP120 manipulates bacteremia to facilitate tick acquisition |
| title_short | Ehrlichia effector TRP120 manipulates bacteremia to facilitate tick acquisition |
| title_sort | ehrlichia effector trp120 manipulates bacteremia to facilitate tick acquisition |
| topic | Ehrlichia japonica TRP120 bacteremia tick acquisition/transmission blood mouse |
| url | https://journals.asm.org/doi/10.1128/mbio.00476-24 |
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