33 research outputs found
Nanomechanical detection of antibiotic-mucopeptide binding in a model for superbug drug resistance
The alarming growth of the antibiotic-resistant superbugs
methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant
Enterococcus (VRE) is driving the development of new technologies to
investigate antibiotics and their modes of action. We report the label-free
detection of vancomycin binding to bacterial cell wall precursor analogues
(mucopeptides) on cantilever arrays, with 10 nM sensitivity and at clinically
relevant concentrations in blood serum. Differential measurements quantified
binding constants for vancomycin-sensitive and vancomycin-resistant mucopeptide
analogues. Moreover, by systematically modifying the mucopeptide density we
gain new insights into the origin of surface stress. We propose that stress is
a product of a local chemical binding factor and a geometrical factor
describing the mechanical connectivity of regions affected by local binding in
terms of a percolation process. Our findings place BioMEMS devices in a new
class of percolative systems. The percolation concept will underpin the design
of devices and coatings to significantly lower the drug detection limit and may
also impact on our understanding of antibiotic drug action in bacteria.Comment: Comments: This paper consists of the main article (6 pages, 5
figures) plus Supplemental Material (6 pages, 3 figures). More details are
available at http://www.london-nano.co
Role of topoisomerase mutations and efflux in fluoroquinolone resistance of Bacteroides fragilis clinical isolates and laboratory mutants.
Twelve laboratory mutants and 32 ciprofloxacin-resistant isolates of Bacteroides fragilis were examined for the mechanism(s) of fluoroquinolone resistance. Five mutants had mutations in gyrA. One mutant and two clinical isolates contained a mutation in gyrB. Eight mutants and five clinical isolates accumulated significantly less ciprofloxacin than did wild-type isolates; the mutants and clinical isolates were restored to wild-type characteristics when carbonyl cyanide m-chlorophenylhydrazone was used