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Moonlighting Effects of the Trehalose Biosynthesis Pathway Regulate Cell Wall Homeostasis of Aspergillus fumigatus.

紀錄類型:	書目-語言資料,手稿 : Monograph/item
正題名/作者:	Moonlighting Effects of the Trehalose Biosynthesis Pathway Regulate Cell Wall Homeostasis of Aspergillus fumigatus./
作者:	Thammahong, Arsa.
面頁冊數:	1 online resource (477 pages)
附註:	Source: Dissertation Abstracts International, Volume: 79-01(E), Section: B.
Contained By:	Dissertation Abstracts International79-01B(E).
標題:	Microbiology. -
電子資源:	click for full text (PQDT)
ISBN:	9780355168167

Moonlighting Effects of the Trehalose Biosynthesis Pathway Regulate Cell Wall Homeostasis of Aspergillus fumigatus.
Thammahong, Arsa.

Moonlighting Effects of the Trehalose Biosynthesis Pathway Regulate Cell Wall Homeostasis of Aspergillus fumigatus. - 1 online resource (477 pages)

Source: Dissertation Abstracts International, Volume: 79-01(E), Section: B.

Thesis (Ph.D.)--Dartmouth College, 2017.

Includes bibliographical references

Aspergillus fumigatus is a human fungal pathogen that can cause severe invasive aspergillosis in immunocompromised hosts. There is an increase in azole-resistant Aspergillus fumigatus strains. Thus, novel specific antifungal drugs are necessary to combat the fungus. Trehalose biosynthesis is one of the pathways found in fungi but not humans. Therefore, this pathway is a candidate for novel antifungal drug development. The canonical fungal trehalose biosynthetic pathway consists of two important enzymes, trehalose-6-phosphate synthase (TpsA/B) and trehalose-6-phosphate phosphatase (OrlA) in addition to two so-called regulatory-like proteins, herein called TslA and TslB.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2018

Mode of access: World Wide Web

ISBN: 9780355168167Subjects--Topical Terms:

591510
Microbiology.
Index Terms--Genre/Form:

554714
Electronic books.

Moonlighting Effects of the Trehalose Biosynthesis Pathway Regulate Cell Wall Homeostasis of Aspergillus fumigatus.
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245 1 0 $a Moonlighting Effects of the Trehalose Biosynthesis Pathway Regulate Cell Wall Homeostasis of Aspergillus fumigatus.
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300 $a 1 online resource (477 pages)
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500 $a Source: Dissertation Abstracts International, Volume: 79-01(E), Section: B.
500 $a Adviser: Robert A. Cramer.
502 $a Thesis (Ph.D.)--Dartmouth College, 2017.
504 $a Includes bibliographical references
520 $a Aspergillus fumigatus is a human fungal pathogen that can cause severe invasive aspergillosis in immunocompromised hosts. There is an increase in azole-resistant Aspergillus fumigatus strains. Thus, novel specific antifungal drugs are necessary to combat the fungus. Trehalose biosynthesis is one of the pathways found in fungi but not humans. Therefore, this pathway is a candidate for novel antifungal drug development. The canonical fungal trehalose biosynthetic pathway consists of two important enzymes, trehalose-6-phosphate synthase (TpsA/B) and trehalose-6-phosphate phosphatase (OrlA) in addition to two so-called regulatory-like proteins, herein called TslA and TslB.
520 $a My thesis focuses on the characterization of TslA and TslB in A. fumigatus and how these trehalose biosynthesis-related proteins regulate cell wall homeostasis, stress responses, and virulence. To characterize TslA and TslB, genetic null mutants of TslA and TslB were generated. Loss of TslA has a significant impact on the trehalose content, cell wall architecture, and interactions with the host immune system. To define causal mechanisms, we generated an epitope-tagged TslA expressing strain and used this strain to identify its interacting partners. We observed a physical interaction between TslA and CsmA, a class V chitin synthase. Loss of TslA affected chitin synthase activity and cellular localization of CsmA.
520 $a We characterized another TslA-interacting partner predicted to impact cell wall homeostasis, a putative protein phosphatase, SsdA. Alteration of ssdA mRNA levels perturbed cell wall homeostasis possibly through alteration of chitin synthase activity and CsmA localization. A ssdA overexpressed strain has a significant attenuation in virulence in invasive pulmonary aspergillosis murine models. These results suggest that TslA may regulate chitin synthase activity and the CsmA localization through SsdA.
520 $a In conclusion, my thesis demonstrates a so-called moonlighting effect of a trehalose biosynthesis-related protein, TslA, that is critical to maintain cell wall homeostasis. This moonlighting function directly impacts the fungal-host interaction and further research is expected to lead us to a better understanding of cell wall homeostasis mechanisms that may yield novel potential drug targets.
533 $a Electronic reproduction. $b Ann Arbor, Mich. : $c ProQuest, $d 2018
538 $a Mode of access: World Wide Web
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650 4 $a Immunology. $3 592892
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710 2 $a Dartmouth College. $b Immunology and Microbiology. $3 1191591
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