The 29th European Congress of Clinical Microbiology & Infectious Diseases, which will take place in Amsterdam, Netherlands, from 13 – 16 April 2019.
ECCMID, as the world’s premier Clinical Microbiology & Infectious Diseases event, brings together experts from many fields to present their latest findings, guidelines and experiences to an audience of over 12,000 colleagues. This year, the Programme Committee has developed a multi-faceted program incorporating keynote lectures and oral sessions, as well as interactive workshops, meet-the-expert sessions, and a wide range of symposia. Be sure to get involved in all of the exciting educational, social and professional events ECCMID has to offer you!
Most Recent Publication
Proof of an Outer Membrane Target of the Efflux Inhibitor Phe-Arg-β-Naphthylamide from Random Mutagenesis.
Phe-Arg-β-naphthylamide (PAβN) has been characterized as an efflux pump inhibitor (EPI) acting on the major multidrug resistance efflux transporters of Gram-negative bacteria, such as AcrB in Eschericha coli. In the present study, in vitro random mutagenesis was used to evolve resistance to the sensitizing activity of PAβN with the aim of elucidating its mechanism of action. A strain was obtained that was phenotypically similar to a previously reported mutant from a serial selection approach that had no efflux-associated mutations. We could confirm that acrB mutations in the new mutant were unrelated to PAβN resistance. The next-generation sequencing of the two mutants revealed loss-of-function mutations in lpxM. An engineered lpxM knockout strain showed up to 16-fold decreased PAβN activity with large lipophilic drugs, while its efflux capacity, as well as the efficacy of other EPIs, remained unchanged. LpxM is responsible for the last acylation step in lipopolysaccharide (LPS) synthesis, and lpxM deficiency has been shown to result in penta-acylated instead of hexa-acylated lipid A. Modeling the two lipid A types revealed steric conformational changes due to underacylation. The findings provide evidence of a target site of PAβN in the LPS layer, and prove membrane activity contributing to its drug-sensitizing potency.