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Understanding the Regulatory Dynamic of the Two-component Systems, PlrSR and BvgAS, During Bordetella Colonization of the Mammalian Respiratory Tract
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| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | Understanding the Regulatory Dynamic of the Two-component Systems, PlrSR and BvgAS, During Bordetella Colonization of the Mammalian Respiratory Tract. |
| 개인저자 | Bone, Mary Ashley. |
| 단체저자명 | The University of North Carolina at Chapel Hill. Microbiology and Immunology. |
| 발행사항 | [S.l.]: The University of North Carolina at Chapel Hill., 2019. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2019. |
| 형태사항 | 137 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-02B. Dissertation Abstract International |
| ISBN | 9781085758536 |
| 학위논문주기 | Thesis (Ph.D.)--The University of North Carolina at Chapel Hill, 2019. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-02, Section: B.
Advisor: Cotter, Peggy A. |
| 이용제한사항 | This item must not be sold to any third party vendors. |
| 요약 | Pertussis is a severe respiratory disease caused by the bacterium Bordetella pertussis. Despite high vaccination coverage, the number of pertussis cases has rebounded in recent years. To combat this disease, more efficacious vaccines and improved knowledge of Bordetella virulence is critical. Bacteria often use two-component systems (TCSs) to coordinate essential cellular processes in response to the diverse environments they encounter. In B. pertussis and the closely related subspecies B. bronchiseptica, the TCS, BvgAS, controls the expression of almost all known virulence factor-encoding genes and is considered the main virulence regulatory system. Recently, another TCS, PlrSR, was identified that is also required for Bordetella infection within the lower respiratory tract (LRT). However, why PlrSR is important for colonization is unknown. Using engineered strains of B. bronchiseptica and genetic reporters, we demonstrated that PlrS is required for the maintenance of BvgAS activity in the lungs of mice, indicating that PlrSR, along with BvgAS, coordinates virulence specifically in the LRT. Moreover, our data indicate that PlrSR may regulate genes that are required for persistence in the LRT independent of BvgAS. Importantly, these genes and their corresponding proteins may serve as new vaccine components or therapeutic targets. We have also shown that the Per-Arnt-Sim (PAS) domain of BvgS is required for BvgS inactivation in the absence of PlrS, indicating that the PAS domain is important for the PlrSR-BvgAS connection and functions as an independent signaling domain. Based on published data and our findings, we hypothesize that PlrSR controls the expression of high-affinity cytochrome oxidases (HACOs) that are required for bacterial respiration and maintenance of BvgAS activity in the LRT. We have demonstrated that two of four HACOs contribute to LRT colonization. However, BvgAS activity is unaffected by the loss of these HACOs and it is unknown if PlrSR regulates the expression of any HACO encoding genes. Together, this work provides a more detailed understanding of the coordinated regulation imposed by PlrSR and BvgAS to promote Bordetella survival within the mammalian host. |
| 일반주제명 | Microbiology. |
| 언어 | 영어 |
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