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035 a| (Sirsi) o1296624461;

035 a| (OCoLC)1296624461;

049 a| EREE;

100 1 a| Palethorpe, Samantha,e| author.?| UNAUTHORIZED;

245 14 a| The respective roles of bfmrs and pmra in stress responses and antibiotic resistance in acinetobacter baumannii /c| by Samantha Palethorpe.;

264 1 a| [Greenville, N.C.] :b| [East Carolina University],c| 2021.;

300 a| 1 online resource (195 pages) :b| illustrations (some color).;

336 a| textb| txt2| rdacontent;

337 a| computerb| c2| rdamedia;

338 a| online resourceb| cr2| rdacarrier;

347 a| text file;

347 b| PDF;

347 c| 2.874 MB;

490 1 a| ECU Brody School of Medicine dissertation;

538 a| System requirements: Adobe Reader.;

538 a| Mode of access: World Wide Web.;

502 b| Ph. D.c| East Carolina Universityd| 2021;

500 a| Presented to the faculty of the Department of Microbiology and Immunology;

500 a| Advisor: Everett C. Pesci;

500 a| Title from PDF t.p. (viewed November 3, 2022).;

520 3 a| The Gram-negative bacterium Acinetobacter baumannii is considered one of the most serious nosocomial pathogens worldwide. Predominantly responsible for ventilator-associated pneumonia, this insidious pathogen typically infects critically ill individuals and patients in long-term care. A. baumannii harbors a myriad of resistance mechanisms to aid its survival in both the environment and the host. Remarkably, A. baumannii does not encode an RpoS sigma factor homolog that is used to control the general stress response by the majority of Gram-negative bacteria. Instead, A. baumannii relies on an intricate regulatory network involving numerous two-component regulatory systems to respond to stress. Two key players that contribute to A. baumannii's "persist and resist" survival mechanisms are the BfmRS and PmrAB two-component regulatory systems. We have demonstrated that the response regulator BfmR can directly activate numerous stress-related pathways. We also provide evidence that the sensor kinase BfmS acts as a phosphatase to negatively regulate BfmR activity. Overall, we show that the BfmRS system harbors the characteristics of a master regulator by controlling the osmotic stress response, the oxidative stress response, the misfolded protein response, csu pili/fimbriae production, capsule polysaccharide biosynthesis, siderophore biosynthesis and transport, type IV pili production, and antibiotic resistance. Additionally, the PmrAB two-component system contributes to antibiotic resistance in A. baumannii. Clinically relevant mutations that arise in the pmrCAB operon often promote resistance to the last resort antibiotic colistin. We biochemically characterized the response regulator PmrA to identify its DNA-binding domain, in addition to the potential PmrA regulon. We also provide the first structural information for the PmrA N-terminal domain. Together, these data allowed us to analyze the structural and dynamic changes in two clinically relevant PmrA point mutants that alter the function of PmrA and promote colistin resistance. Understanding these regulatory mechanisms at a molecular level will allow us to explore novel ways to develop effective antimicrobial agents to combat this serious pathogen.;

504 a| Includes bibliographical references.;

650 2 a| Drug Resistance, Bacterial.=| ^A936476;

650 2 a| Acinetobacter baumannii.=| ^A1451692;

650 2 a| Acinetobacter Infections.=| ^A947188;

655 2 a| Academic Dissertation.0| (DNLM)D019478?| UNAUTHORIZED;

653 a| BfmRS;

653 a| colistin resistance;

653 a| PmrA;

653 a| response regulator;

653 a| stress-response;

653 a| trehalose;

653 a| two-component system;

655 7 a| Academic theses.2| fast0| (OCoLC)fst01726453;

655 7 a| Academic theses.2| lcgft;

655 7 a| Thèses et écrits académiques.2| rvmgf0| (CaQQLa)RVMGF-000001173;

700 1 a| Pesci, Everett C.,e| degree supervisor.?| UNAUTHORIZED;

710 2 a| East Carolina University.b| Department of Microbiology and Immunology.?| UNAUTHORIZED;

830 0 a| ECU Brody School of Medicine dissertation.?| UNAUTHORIZED;

856 40 u| http://hdl.handle.net/10342/9753z| Access via ScholarShip;

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596 a| 1 4;

998 a| 5792251;

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The respective roles of bfmrs and pmra in stress responses and antibiotic resistance in acinetobacter baumannii / by Samantha Palethorpe.

Author/creator	Palethorpe, Samantha author.
Other author	Pesci, Everett C., degree supervisor.
Other author	East Carolina University. Department of Microbiology and Immunology.
Format	Theses and dissertations
Publication	[Greenville, N.C.] : [East Carolina University], 2021.
Description	1 online resource (195 pages) : illustrations (some color).
Supplemental Content	Access via ScholarShip
Subjects	Drug Resistance, Bacterial. Acinetobacter baumannii. Acinetobacter Infections.

Series	ECU Brody School of Medicine dissertation ECU Brody School of Medicine dissertation. UNAUTHORIZED
Summary	The Gram-negative bacterium Acinetobacter baumannii is considered one of the most serious nosocomial pathogens worldwide. Predominantly responsible for ventilator-associated pneumonia, this insidious pathogen typically infects critically ill individuals and patients in long-term care. A. baumannii harbors a myriad of resistance mechanisms to aid its survival in both the environment and the host. Remarkably, A. baumannii does not encode an RpoS sigma factor homolog that is used to control the general stress response by the majority of Gram-negative bacteria. Instead, A. baumannii relies on an intricate regulatory network involving numerous two-component regulatory systems to respond to stress. Two key players that contribute to A. baumannii's "persist and resist" survival mechanisms are the BfmRS and PmrAB two-component regulatory systems. We have demonstrated that the response regulator BfmR can directly activate numerous stress-related pathways. We also provide evidence that the sensor kinase BfmS acts as a phosphatase to negatively regulate BfmR activity. Overall, we show that the BfmRS system harbors the characteristics of a master regulator by controlling the osmotic stress response, the oxidative stress response, the misfolded protein response, csu pili/fimbriae production, capsule polysaccharide biosynthesis, siderophore biosynthesis and transport, type IV pili production, and antibiotic resistance. Additionally, the PmrAB two-component system contributes to antibiotic resistance in A. baumannii. Clinically relevant mutations that arise in the pmrCAB operon often promote resistance to the last resort antibiotic colistin. We biochemically characterized the response regulator PmrA to identify its DNA-binding domain, in addition to the potential PmrA regulon. We also provide the first structural information for the PmrA N-terminal domain. Together, these data allowed us to analyze the structural and dynamic changes in two clinically relevant PmrA point mutants that alter the function of PmrA and promote colistin resistance. Understanding these regulatory mechanisms at a molecular level will allow us to explore novel ways to develop effective antimicrobial agents to combat this serious pathogen.
General note	Presented to the faculty of the Department of Microbiology and Immunology
General note	Advisor: Everett C. Pesci
General note	Title from PDF t.p. (viewed November 3, 2022).
Dissertation note	Ph. D. East Carolina University 2021
Bibliography note	Includes bibliographical references.
Technical details	System requirements: Adobe Reader.
Technical details	Mode of access: World Wide Web.
Genre/form	Academic theses.
Genre/form	Academic theses.
Genre/form	Thèses et écrits académiques.

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The respective roles of bfmrs and pmra in stress responses and antibiotic resistance in acinetobacter baumannii / by Samantha Palethorpe.

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