Mutations in the central cavity of the MexB homologue EmhB of Pseudomonas fluorescence and AcrB from E. coli significantly affected the efflux of substrates (Yu et al., 2003; Hearn et al., 2006). In addition, it has previously been shown that extrusion of hydrophobic substrates mediated by MexA-MexB-OprM mainly takes

place from the interior of the cytoplasmic membrane (Ocaktan et al., 1997). Hence, it is possible that, in addition to the periplasmic pathway, an alternative efflux path exists for substrates. The phenylalanine residues investigated in this study might be the start of a drug efflux pathway facing STA-9090 the cytoplasm. This putative pathway seems not to be linked with the periplasmic pathway as disrupting the cytoplasmic-binding site has no effect on the transport of periplasmically acting antibiotics. The exact nature of this putative pathway, for instance if drugs would be transported through the individual protomers or through the central pore, remains to be determined and is the subject of a follow-up study. In this study, we have for the first time provided a biochemical characterization of the conserved phenylalanine

residues in MexB that forms part of a cytoplasmic-binding site for drugs. The data obtained provides a better understanding of the molecular mechanism of substrate efflux by this important class of multidrug efflux proteins. This work was funded by a Royal Society Dorothy Hodgkin Fellowship to Branched chain aminotransferase HV and a Royal Society http://www.selleckchem.com/products/bay80-6946.html Research Grant.

TO is the recipient of a Cambridge Trust scholarship, an Adam Glinsman award and a Faculty for the Future Fellowship from the Schlumberger Foundation. “
“Human respiratory syncytial virus (RSV) sometimes causes acute and severe lower respiratory tract illness in infants and young children. The platelet-activating factor (PAF) receptor, which is a receptor for Streptococcus pneumoniae and Haemophilus influenzae, is upregulated by RSV infection in the pulmonary epithelial cell line A549. Fosfomycin, an antimicrobial agent, significantly suppressed PAF receptor induction by RSV infection at the mRNA and cell surface expression levels. Fosfomycin also suppressed RSV-induced adhesion of fluorescence-labeled S. pneumoniae and H. influenzae cells, as determined by flow cytometry and fluorescence microscopy. The RSV-induced bacterial adhesion was suggested to be host-PAF-receptor and bacterial-phosphocholine mediated. Fosfomycin, which has been shown to exhibit antimicrobial and immunomodulatory activities, was found here to suppress adhesion by disease-causing bacteria. Thus, fosfomycin might prevent secondary bacterial infection during RSV infection. Human respiratory syncytial virus (RSV) is one of the most important infectious agents causing acute lower respiratory tract illness, such as bronchiolitis and pneumonia, in infants and young children.