Multidrug resistance and its regulation in Enterococcus faecalis

PhD ceremony: Mr. M. Tariq, 11.00 uur, Aula Academiegebouw, Broerstraat 5, Groningen

Dissertation: Multidrug resistance and its regulation in Enterococcus faecalis

Promotor(s): prof. J. Kok

Faculty: Mathematics and Natural Sciences

Prevention and eradication of infections caused by multidrug resistant bacteria are among the major public health challenges of the 21st century. The opportunistic pathogen Enterococcus faecalis is a leading cause of hospital-acquired, sometimes life-threatening, infections associated with lengthened hospital stays. The thesis of Muhammad Tariq shows that the ABC-type MDR system EmrCD is responsible for MDR in E. faecalis. EmrR has been investigated with respect to the regulation of the emrCD genes. In E. faecalis wild-type emrR and emrCD are transcribed during the logarithmic phase of growth, independent of drug presence. EmrR activates the transcription of emrCD and when drug molecules are present in the environment and enter the cell, they are subsequently extruded from the cells by the EmrCD transporter. Biofilms are important with respect to drug resistance as the dense matrix seems to have a role in protecting the cells from antimicrobial agents. Heterogeneity in the presence of the endocarditis and biofilm-associated Ebp pili has been correlated to that in cell surface charge. Tariq shows also that cells with pili are less negative than non-pilated cells and that cultures homogenous for pilus presence or absence were also homogenous for zeta potential. Several genes for cell-surface and regulatory proteins that are relevant in E. faecalis infection, such as adhesion, resistance to immune response, colonisation, and signalling were identified in the ERA-net Pathogenomics programme, as described inthe Addendum. Tariqs thesis offers a roadmap for future research on enterococci that could contribute to selection of potential targets for preventive and therapeutic anti-enterococcal regimens.