PhD ceremony: ms. H. Agustiandari, 13.15 uur, Academiegebouw, Broerstraat 5, Groningen
Thesis: Regulation of multidrug resistance in Lactococcus lactis
Promotor(s): prof. A.J.M. Driessen
Faculty: Mathematics and Natural Sciences
Herfita Augustiandari studied the regulation of multidrug resistance in Lactococcus lactis. The multidrug resistance (MDR) phenomenon is the ability of cells to develop resistance against a wide range of structurally unrelated toxic molecules. MDR is caused by the (over) expression of transporters that expel these compounds from the cell. Multidrug resistance has lead to multiple complications in the treatment of for instance cancer or infectious diseases. The introduction and improper use of antibiotics have led to a selection of bacteria that by mutation(s) in their genome developed resistance mechanisms which allowed them to survive under this severe antibiotics pressure. In short the most important results of the research of Augustiandari are: She has elucidated the regulation mechanism of the major multidrug transporter LmrCD by the transcriptional regulator termed LmrR in Lactococcus lactis. She also showed that LmrR regulates its own expression but in a very different manner than to LmrCD. The crystal structures of apo LmrR and LmrR bound drugs (Hoechst 33342 and Daunomycin) were solved at 2.0Å and 2.2Å resolution, respectively where she found the presence of a symmetric big flat-shape central pore responsible for ligand(s) binding. This feature is unique and has not been seen before for the other well characterized bacterial transcriptional regulator. These new insights will be useful for the further development of the new antimicrobial compounds.
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