Showing papers by "Brian Dougherty published in 2001"
TL;DR: A motif identified within the signal peptide of proteins is potentially involved in targeting these proteins to the cell surface of low–guanine/cytosine Gram-positive species.
Abstract: The 2,160,837-base pair genome sequence of an isolate of Streptococcus pneumoniae, a Gram-positive pathogen that causes pneumonia, bacteremia, meningitis, and otitis media, contains 2236 predicted coding regions; of these, 1440 (64%) were assigned a biological role. Approximately 5% of the genome is composed of insertion sequences that may contribute to genome rearrangements through uptake of foreign DNA. Extracellular enzyme systems for the metabolism of polysaccharides and hexosamines provide a substantial source of carbon and nitrogen for S. pneumoniae and also damage host tissues and facilitate colonization. A motif identified within the signal peptide of proteins is potentially involved in targeting these proteins to the cell surface of low-guanine/cytosine (GC) Gram-positive species. Several surface-exposed proteins that may serve as potential vaccine candidates were identified. Comparative genome hybridization with DNA arrays revealed strain differences in S. pneumoniae that could contribute to differences in virulence and antigenicity.
1,409 citations
TL;DR: Inhibiting bacterial efflux with a non-antibiotic inhibitor would restore activity of an antibiotic subject to efflux (similar to the use of β-lactamase inhibitors to combat β- lactamases production by bacteria).
Abstract: Efflux is the process in which bacteria transport compounds outside the cell which are potentially toxic, such as drugs or chemicals or compounds. Efflux pumps can be identified not only by biochemical, microbiological, or molecular means but with the availability of microbial genomic sequences, by the application of bioinformatics analysis of DNA sequences for key conserved structure motifs. Efflux has been identified as a relevant contributor to bacterial resistance in the clinic and is now recognised as one of the most important causes of intrinsic antibiotic resistance in bacteria, especially in Pseudomonas aeruginosa. With the recognition of efflux as a major factor in bacterial resistance, several companies have invested in the identification and development of bacterial efflux pump inhibitors. Among those, Microcide, Pfizer, Paratek and several academic laboratories are in the process of exploring efflux pump inhibitors from synthetic, natural products and peptidomimetics. Inhibiting bacterial efflux with a non-antibiotic inhibitor would restore activity of an antibiotic subject to efflux (similar to the use of beta-lactamase inhibitors to combat beta-lactamase production by bacteria). The feasibility of such an approach has been experimentally demonstrated in vitro and in vivo for efflux reversal of levofloxacin.
73 citations