The in-vivo Evolution of Burkholderia multivorans in a Cystic Fibrosis patient

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Harrison, S. (2021). The in-vivo Evolution of Burkholderia multivorans in a Cystic Fibrosis patient. Unc Charlotte Electronic Theses And Dissertations.
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Abstract

ABSTRACT Burkholderia multivorans is an opportunistic pathogen that poses a health risk to patients with cystic fibrosis (CF). The use of broad-range antibiotics to combat chronic bacterial lung infections has led to the evolution of antibiotic-resistant and multi-drug resistant Burkholderia multivorans (ABR and MDR). Understanding how these bacteria respond genetically to antibiotic therapy would be useful in optimizing drug therapy as well as to provide insight into how an established, complex, and chronic bacterial community adapts in response to multiple drug treatments. To this extent, we analyzed the in vivo evolution of B. multivorans during multiple pulmonary exacerbations over three years in a CF patient who underwent extensive antibiotic treatment. We found the population diversified into at least two coexisting lineages with an average of 2.7 SNPs/year. Within these lineages, we found that 12 genes had a significant excess of mutations. Importantly, we observed an excess of mutations in the dacB gene and one in ampD, in strains isolated following IV administration of ceftazidime (CAZ) during a 2-week hospitalization. Both dacB and ampD have previously been reported to regulate β-lactamase expression, where deactivating mutants leads to hyper-inducible AmpC and/or PenA in other Burkholderia and gram-negative bacteria. These data suggest possible β-lactamase regulators' importance to resistance to β-lactam antibiotics in B. multivorans.

Details
Author

Harrison, Sarah

Title

The in-vivo Evolution of Burkholderia multivorans in a Cystic Fibrosis patient

Physical Description

1 online resource (43 pages) : PDF

Date

2021

Degree Granting Institution

University of North Carolina at Charlotte

Abstract

ABSTRACT Burkholderia multivorans is an opportunistic pathogen that poses a health risk to patients with cystic fibrosis (CF). The use of broad-range antibiotics to combat chronic bacterial lung infections has led to the evolution of antibiotic-resistant and multi-drug resistant Burkholderia multivorans (ABR and MDR). Understanding how these bacteria respond genetically to antibiotic therapy would be useful in optimizing drug therapy as well as to provide insight into how an established, complex, and chronic bacterial community adapts in response to multiple drug treatments. To this extent, we analyzed the in vivo evolution of B. multivorans during multiple pulmonary exacerbations over three years in a CF patient who underwent extensive antibiotic treatment. We found the population diversified into at least two coexisting lineages with an average of 2.7 SNPs/year. Within these lineages, we found that 12 genes had a significant excess of mutations. Importantly, we observed an excess of mutations in the dacB gene and one in ampD, in strains isolated following IV administration of ceftazidime (CAZ) during a 2-week hospitalization. Both dacB and ampD have previously been reported to regulate β-lactamase expression, where deactivating mutants leads to hyper-inducible AmpC and/or PenA in other Burkholderia and gram-negative bacteria. These data suggest possible β-lactamase regulators' importance to resistance to β-lactam antibiotics in B. multivorans.

Genre

masters theses

Subjects--Topics

Biology
Microbiology
Bioinformatics

Degree

M.S.

Keywords

Antibiotic Resistance
Burkholderia
Cystic Fibrosis
Evolution

Subject Area

Biology

Advisor(s)

Steck, Todd

Committee Members

Sung, Way
Parrow, Matthew

Degree Note

Thesis (M.S.)--University of North Carolina at Charlotte, 2021.

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Rights Holder Information

Copyright is held by the author unless otherwise indicated.

Identifier

Harrison_uncc_0694N_12809

Permalink

http://hdl.handle.net/20.500.13093/etd:2597