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Identification and Characterization of a Novel Stress Response Pathway in Acinetobacter baumannii.

Record Type:	Language materials, manuscript : Monograph/item
Title/Author:	Identification and Characterization of a Novel Stress Response Pathway in Acinetobacter baumannii./
Author:	Gebhardt, Michael John.
Description:	1 online resource (252 pages)
Notes:	Source: Dissertation Abstracts International, Volume: 78-11(E), Section: B.
Contained By:	Dissertation Abstracts International78-11B(E).
Subject:	Microbiology. -
Online resource:	click for full text (PQDT)
ISBN:	9780355075274

Identification and Characterization of a Novel Stress Response Pathway in Acinetobacter baumannii.
Gebhardt, Michael John.

Identification and Characterization of a Novel Stress Response Pathway in Acinetobacter baumannii. - 1 online resource (252 pages)

Source: Dissertation Abstracts International, Volume: 78-11(E), Section: B.

Thesis (Ph.D.)

Includes bibliographical references

Bacterial pathogenesis requires an invading bacterium to sense and adapt to the harsh environments encountered inside the human host. This is especially true for opportunistic pathogens, such as Acinetobacter baumannii, an organism that is rapidly emerging as a serious source of hospital acquired infections, in part due to the high levels of antibiotic resistance harbored by contemporary clinical isolates. A key limitation to combatting A. baumannii is that a thorough understanding of the molecular mechanisms that underlie A. baumannii pathogenesis is lacking.

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

Mode of access: World Wide Web

ISBN: 9780355075274Subjects--Topical Terms:

591510
Microbiology.
Index Terms--Genre/Form:

554714
Electronic books.

Identification and Characterization of a Novel Stress Response Pathway in Acinetobacter baumannii.
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100 1 $a Gebhardt, Michael John. $3 1183404
245 1 0 $a Identification and Characterization of a Novel Stress Response Pathway in Acinetobacter baumannii.
264 0 $c 2017
300 $a 1 online resource (252 pages)
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500 $a Source: Dissertation Abstracts International, Volume: 78-11(E), Section: B.
500 $a Adviser: Howard A. Shuman.
502 $a Thesis (Ph.D.) $c The University of Chicago $d 2017.
504 $a Includes bibliographical references
520 $a Bacterial pathogenesis requires an invading bacterium to sense and adapt to the harsh environments encountered inside the human host. This is especially true for opportunistic pathogens, such as Acinetobacter baumannii, an organism that is rapidly emerging as a serious source of hospital acquired infections, in part due to the high levels of antibiotic resistance harbored by contemporary clinical isolates. A key limitation to combatting A. baumannii is that a thorough understanding of the molecular mechanisms that underlie A. baumannii pathogenesis is lacking.
520 $a In order to identify potential virulence determinants harbored by A. baumannii, I employed a large-scale forward genetic screen known as transposon insertion sequencing, or TnSeq, with A. baumannii strain AB5075, a contemporary isolate that exhibits both enhanced virulence and resistance to multiple classes of antibiotics. The TnSeq screen identified 300 genes that are specifically required for the survival and/or growth of A. baumannii inside Galleria mellonella larvae, an established insect infection model for studying microbial pathogenesis. Importantly, the genes identified in the screen encompassed many of the previously characterized virulence determinants of A. baumannii and, more importantly, also uncovered several novel genes that are critical for A. baumannii pathogenesis.
520 $a My follow-up studies focus on genes involved with transcriptional regulation and reveal that several of the transcription factors required for growth inside the Galleria larvae, which are given the name 'gig' (for Growth in Galleria), are also required for resistance to antibiotics and environmental stress. Using a combination of genetic and biochemical approaches, I demonstrate that GigA and GigB comprise a previously undiscovered signal transduction pathway required for not only virulence in the G. mellonella model, but also for resistance to environmental stress and antibiotic exposure. Additionally, I provide evidence that GigA/GigB are required for establishing an appropriate transcriptional response to antibiotic exposure. My studies also uncover a direct link between GigA/GigB and the nitrogen phosphotransferase system (PTSNtr), a well-conserved metabolic sensing pathway. These findings suggest that GigA/GigB are master regulators of a global stress response and the coupling of the GigA/GigB signaling axis to the PTS Ntr allows A. baumannii to integrate cellular metabolic status with environmental cues.
533 $a Electronic reproduction. $b Ann Arbor, Mich. : $c ProQuest, $d 2018
538 $a Mode of access: World Wide Web
650 4 $a Microbiology. $3 591510
650 4 $a Genetics. $3 578972
650 4 $a Molecular biology. $3 583443
655 7 $a Electronic books. $2 local $3 554714
690 $a 0410
690 $a 0369
690 $a 0307
710 2 $a ProQuest Information and Learning Co. $3 1178819
710 2 $a The University of Chicago. $b Microbiology. $3 1183405
773 0 $t Dissertation Abstracts International $g 78-11B(E).
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10259107 $z click for full text (PQDT)