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Genomic Characterization of a Burkholderia contaminans Outbreak

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2020-06-24

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Osmulski, Sarah. 2020. Genomic Characterization of a Burkholderia contaminans Outbreak. Doctoral dissertation, Harvard Medical School.

Abstract

Burkholderia contaminans is a Gram-negative multidrug resistant bacterium that is an emerging pathogen in patients with cystic fibrosis (CF) and has been previously associated with outbreaks related to contamination of pharmaceutical products. In 2016, B. contaminans was implicated in an outbreak of infections in non-CF critically ill patients. Bacterial whole genome sequencing allowed investigators to trace the source of this outbreak to contaminated liquid docusate sodium. Further analysis of the sequence variants identified evidence of evolution of the bacteria from the pharmaceutical factory contaminant to the individual patient isolates. Here, we investigated insertions, deletions, and single nucleotide polymorphisms (SNPs) in key genes (mpl, dfrA, nemR) to understand their role in increased antibiotic and disinfectant resistance. Our results show that mutations in mpl induce ceftazidime resistance that is ß-lactamase dependent, that a D29E variant in DHFR is not sufficient to induce trimethoprim-sulfamethoxazole (TMP-SMX) resistance, and that isolates with mutations in nemR trended towards increased resistance to bleach in vitro.

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Burkholderia cepacia complex, Burkholderia contaminans, pharmaceutical contamination, antibiotic resistance

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