Academic Journal
Evaluation of Mycobacterium avium subsp. paratuberculosis isocitrate lyase (IcL) and ABC transporter (BacA) knockout mutants as vaccine candidates
| العنوان: | Evaluation of Mycobacterium avium subsp. paratuberculosis isocitrate lyase (IcL) and ABC transporter (BacA) knockout mutants as vaccine candidates |
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| المؤلفون: | Eshraghisamani, Razieh, Arrazuria, Rakel, Luo, Lucy, De Buck, Jeroen |
| المساهمون: | Agriculture Funding Consortium |
| المصدر: | Frontiers in Cellular and Infection Microbiology ; volume 13 ; ISSN 2235-2988 |
| بيانات النشر: | Frontiers Media SA |
| سنة النشر: | 2023 |
| المجموعة: | Frontiers (Publisher - via CrossRef) |
| الوصف: | There has been little success in controlling Johne’s disease, caused by Mycobacterium avium subsp. paratuberculosis , due to suboptimal diagnostics and the ineffectiveness of available vaccines. By knocking out BacA and IcL , genes required for MAP survival in dairy calves, two live-attenuated vaccine candidates were created. This study evaluated the host-specific attenuation of MAP IcL and BacA mutants in mouse and calf models, as well as the elicited immune responses. Deletion mutants were generated in MAP strain A1-157 through specialized transduction and found viable in vitro . First, the mutants’ attenuation and elicited cytokine secretion were assessed in a mouse model, 3 weeks after intraperitoneal inoculation with MAP strains. Later, vaccine strains were assessed in a natural host infection model where calves received 10 9 CFU oral dose of MAP wild-type or mutant strains at 2 weeks old. Transcription levels of cytokines in PBMCs were evaluated at 12-, 14-, and 16-weeks post-inoculation (WPI) and MAP colonization in tissue was assessed at 4.5 months after inoculation. Whereas both vaccine candidates colonized mouse tissues similarly to wild-type strain, both failed to persist in calf tissues. In either mouse or calf models, gene deletion did not reduce immunogenicity. Instead, inoculation with Δ BacA induced a greater upregulation of proinflammatory cytokines than Δ IcL and wild-type in both models and a greater expansion of cytotoxic and memory T-cells than uninfected control in calves. Δ BacA and wild-type strains significantly increased secretion of IP-10, MIG, TNFα, and RANTES in mice serum compared to uninfected control. This agreed with upregulation of IL-12, IL-17, and TNFα in calves inoculated with Δ BacA at all time points. The Δ BacA also gave rise to greater populations of CD4+CD45RO+, and CD8+ cells than uninfected control calves at 16 WPI. Low survival rate of MAP in macrophages co-incubated with PBMCs isolated from the Δ BacA group indicated that these cell populations are capable of killing ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| DOI: | 10.3389/fcimb.2023.1149419 |
| DOI: | 10.3389/fcimb.2023.1149419/full |
| الاتاحة: | http://dx.doi.org/10.3389/fcimb.2023.1149419 https://www.frontiersin.org/articles/10.3389/fcimb.2023.1149419/full |
| Rights: | https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.F2E7D720 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3389/fcimb.2023.1149419 |
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