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Unraveling gene regulation of MDR and ABC-transporters in Gram-positive bacteria

Wang, H. (2012) Unraveling gene regulation of MDR and ABC-transporters in Gram-positive bacteria. Bachelor's Thesis, Biology.

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Bacteria become more resistant to current antibiotics which means less antibiotics are available to treat bacterial infections. New antibiotics are needed and can be found by understanding the mechanism of resistance and developing antimicrobials that interfere with it. There are different mechanisms that confer antibiotic resistance and next to the protection of the cell wall, drug efflux is the most important mechanism in Gram-positive bacteria because it confers resistance to many structurally diverse antimicrobials. Fitness of cells is lowered if the efflux transporters are expressed unnecessary and, therefore, gene expression has to be regulated in accordance to changes in the environment. The most straightforward way to regulate drug efflux transporters is by direct induction or repression of its gene. Inhibitory proteins such as QacR and LmrR repress qacA and lmrC/D, respectively, in absence of antimicrobials and release the DNA once bacteria are challenged with antibiotics. Inducing proteins, on the other hand, induce gene transcription once it is bound to DNA and a substrate. Global modulator proteins MgrA and NorG regulate many processes, including the drug efflux genes norA/B/C, tet38 and abcA. Mutations in DNA, and therefore in mRNA, can also cause upregulation of gene expression as well. Bmr3 and NorA are upregulated by an increased mRNA half-time caused by a point mutation. The mutation in bmr3 and norA leads to a stabilization of their transcripts which upregulates translation. This thesis shows that genes can be regulated on different levels and in different ways which induce resistance to antimicrobials.

Item Type: Thesis (Bachelor's Thesis)
Degree programme: Biology
Thesis type: Bachelor's Thesis
Language: English
Date Deposited: 15 Feb 2018 07:48
Last Modified: 15 Feb 2018 07:48

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