Assessing the likelihood of meropenem resistance acquisition in Burkholderia pseudomallei via lateral gene transfer from Burkholderia ubonensis

Nottingham, Roxanne (2023) Assessing the likelihood of meropenem resistance acquisition in Burkholderia pseudomallei via lateral gene transfer from Burkholderia ubonensis. Masters thesis, Northern Arizona University.

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Abstract

The disease melioidosis is caused by the environmental bacterium Burkholderia pseudomallei. Treatment for this disease can be complex, as B. pseudomallei is intrinsically resistant to multiple broad-spectrum antimicrobials . However, decades of research have resulted in a more effective treatment regimen, with meropenem reserved for patients in Intensive Care Units suffering from severe melioidosis. Burkholderia ubonensis, a distantly related non-pathogenic bacterium, is often co-isolated with B. pseudomallei from soil. It has been suggested that ~50% of B. pseudomallei strains are naturally competent and both species can acquire new genomic content via lateral gene transfer (LGT) and can also display resistance to a variety of antimicrobials, with B. ubonensis occasionally displaying high levels of intrinsic resistance to meropenem. The goal of this study was to determine if B. ubonensis can serve as a source for meropenem resistance in B. pseudomallei via LGT.Meropenem resistance was evaluated in a set of 122 phylogenetically and spatially diverse environmental isolates of B. pseudomallei using a broth microdilution method. All strains had an MIC of ≤ 2 µg/ml and were determined to be susceptible. A series of transformation experiments was conducted using an attenuated strain of B. pseudomallei and a genetically modified strain of B. ubonensis. No growth was observed when B. pseudomallei was exposed to B. ubonensis DNA for a short period of time and subsequently plated onto agar plates containing subinhibitory levels of meropenem (20 µg/ml). In addition, clinically significant increases in meropenem resistance were not observed in generated B. pseudomallei mutants containing the specific genes that confer meropenem resistance in B. ubonensis. Environmental isolates of B. pseudomallei are largely susceptible to meropenem and cannot acquire and express meropenem resistance genes from environmental B. ubonensis DNA.

Item Type:	Thesis (Masters)
Publisher’s Statement:	© Copyright is held by the author. Digital access to this material is made possible by the Cline Library, Northern Arizona University. Further transmission, reproduction or presentation of protected items is prohibited except with permission of the author.
Keywords:	competency; environment; LGT; LS-BSR; Burkholderia pseudonmallei; meropenem; Burkholdeeria ubonensis; microdilution
Subjects:	R Medicine > RB Pathology
MeSH Subjects:	B Organisms > B03 Bacteria
NAU Depositing Author Academic Status:	Student
Department/Unit:	Graduate College > Theses and Dissertations College of the Environment, Forestry, and Natural Sciences > Biological Sciences
Date Deposited:	18 Jun 2025 22:57
Last Modified:	18 Jun 2025 22:57
URI:	https://openknowledge.nau.edu/id/eprint/6178

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