, 2002), and yet in RRSA16, marked vancomycin resistance emerged with ramoplanin resistance. Limited access to lipid II via restricted diffusion through the thickened cell wall to the outer membrane or by decoy titration through the overproduction of peptidoglycan precursors containing
an intact pyrophosphate may explain the parallel resistance phenotypes observed. Because antibiotic susceptibility is significantly restored in the strain R16-18d, it is likely that a significant subset of events leading to ramoplanin-resistant phenotype is transcriptionally controlled. We also determined that RRSA16 had increased resistance to the lantibiotic nisin (Table 2). The site of nisin action is lipid II, and similar to ramoplanin, nisin binding requires the pyrophosphate moiety (Bonev et al., 2004; Hsu et al., 2004). However, the primary mechanism of nisin Pexidartinib manufacturer action is not by substrate inhibition of transglycosylation; rather, stable pores composed of nisin and lipid II molecules are formed in the bacterial membrane, resulting in lysis (Brotz et al., 1998; Breukink et al., 1999, 2003; van Heusden et al., 2002; Hasper et al., 2004). Decreased S. aureus susceptibility to nisin and other cationic peptide antimicrobials is confirmed by increased selleck inhibitor expression of the dlt operon resulting
in increased d-alanylation of teichoic acids, resulting in a more cationic cell envelope (Peschel et al., 1999; Sass & Bierbaum, 2009). Increased d-alanylation of teichoic selleck products acids may influence susceptibility to ramoplanin as it is a cationic peptide, requiring ornithine at position 10 for molecular recognition of the lipid II pyrophosphate via an electrostatic interaction (Cudic et al., 2002; Nam et al., 2007). Furthermore, alteration of the teichoic acid structure is known to modulate autolysin activity (Fedtke et al., 2007). Because ramoplanin and nisin each bind the pyrophosphate moiety of lipid II and are both cationic, one hypothesis is that some component of the adaptations and mutations generated by serial passage in ramoplanin may have altered the ability of cationic peptides to associate with lipid II and/or the cell envelope. Further
study of RRSA16 and R16-18d should provide an insight into the molecular mechanism of ramoplanin resistance in S. aureus and may lead to strategies for the prevention of antimicrobial resistance during clinical use. This work was generously supported by US Public Health Service grant AI46611 from the National Institutes of Health to D.G.M. “
“Bartonella henselae is an emerging gram-negative facultative intracellular pathogen transmitted via Ctenocephalides felis (cat fleas) or cat scratches. Bartonellosis is present mainly in the form of cat scratch disease (CSD), bacillary angiomatosis and infective endocarditis (IE). The methods used to diagnose B. henselae rely on culturing, immunofluorescent assays and molecular techniques.