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Recent Advances in Multi-Drug Resistance (MDR) Efflux Pump Inhibitors of Gram-Positive Bacteria S. aureus
Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University-Medical College / ul. Medyczna 9, 31-688 Cracow, Poland
* Author to whom correspondence should be addressed.
Received: 4 January 2013; in revised form: 29 January 2013 / Accepted: 30 January 2013 / Published: 5 February 2013
Abstract: The paper focuses on recent achievements in the search for new chemical compounds able to inhibit multidrug resistance (MDR) mechanisms in Gram-positive pathogens. An analysis of the results of the search for new efflux pump inhibitors (EPIs) for Gram-positive bacteria, which have been performed over the last decade, indicates that almost all efforts are focused on the NorA (MFS) efflux pump in S. aureus. Considering the chemical structures of the NorA EPIs that have been identified, it can be observed that the most active agents belong to the families of compounds possessing conjugated double bonds, e.g., chalcones, piperine-like compounds, N-cinnamoylphenalkylamides or citral amide derivatives. Indole-, dihydronaphthyl-, 2-chloro-5-bromo-phenyl- or piperidine moieties seem to be profitable for the EPI properties, as well. These results, together with an increasing knowledge about a variety of efflux pumps that are involved in MDR of Gram-positive pathogens underline that further search for new EPIs should pay more attention to develop MDR efflux protein targets, including SMR, MATE, ABC or other members of the MFS family.
Keywords: bacterial multidrug resistance; MDR; efflux pump inhibitors; EPIs; NorA
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Handzlik, J.; Matys, A.; Kieć-Kononowicz, K. Recent Advances in Multi-Drug Resistance (MDR) Efflux Pump Inhibitors of Gram-Positive Bacteria S. aureus. Antibiotics 2013, 2, 28-45.
Handzlik J, Matys A, Kieć-Kononowicz K. Recent Advances in Multi-Drug Resistance (MDR) Efflux Pump Inhibitors of Gram-Positive Bacteria S. aureus. Antibiotics. 2013; 2(1):28-45.
Handzlik, Jadwiga; Matys, Anna; Kieć-Kononowicz, Katarzyna. 2013. "Recent Advances in Multi-Drug Resistance (MDR) Efflux Pump Inhibitors of Gram-Positive Bacteria S. aureus." Antibiotics 2, no. 1: 28-45.