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Titolo:
Design of a novel mammalian screening system for the detection of bioavailable, non-cytotoxic streptogramin antibiotics
Autore:
Aubel, D; Morris, R; Lennon, B; Rimann, M; Kaufmann, H; Folcher, M; Bailey, JE; Thompson, CJ; Fussenegger, M;
Indirizzi:
ETH Zurich, Swiss Fed Inst Technol, Inst Biotechnol, CH-8093 Zurich, Switzerland ETH Zurich Zurich Switzerland CH-8093 chnol, CH-8093 Zurich, Switzerland Univ Basel, Inst Technol, IUTA, Dept Genie Biol, F-69200 Villeurbanne, France Univ Basel Villeurbanne France F-69200 iol, F-69200 Villeurbanne, France Univ Basel, Biozentrum, Dept Microbiol, CH-4056 Basel, Switzerland Univ Basel Basel Switzerland CH-4056 crobiol, CH-4056 Basel, Switzerland
Titolo Testata:
JOURNAL OF ANTIBIOTICS
fascicolo: 1, volume: 54, anno: 2001,
pagine: 44 - 55
SICI:
0021-8820(200101)54:1<44:DOANMS>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
MULTIDRUG-RESISTANCE GENE; PROMOTER INDUCING ACTIVITY; STREPTOMYCES SP SF2741; ENCODING RESISTANCE; EXPRESSION; PROTEIN; BIOSYNTHESIS; BINDING; QUINUPRISTIN/DALFOPRISTIN; PRISTINAESPIRALIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
51
Recensione:
Indirizzi per estratti:
Indirizzo: Fussenegger, M ETH Zurich, Swiss Fed Inst Technol, Inst Biotechnol, CH-8093 Zurich, Switzerland ETH Zurich Zurich Switzerland CH-8093 Zurich, Switzerland
Citazione:
D. Aubel et al., "Design of a novel mammalian screening system for the detection of bioavailable, non-cytotoxic streptogramin antibiotics", J ANTIBIOT, 54(1), 2001, pp. 44-55

Abstract

Screening and development of new antibiotic activities to counteract the increasing prevalence of multidrug-resistant (MDR) human pathogenic bacteriahas once again become a priority in human chemotherapy. Here we describe anovel mammalian cell culture-based screening platform for the detection ofstreptogramin antibiotics. Quinupristin-dalfopristin (Synercid(R)),a synthetically modified streptogramin, is presently the sole effective agent in the treatment of some MDR nosocomial infections. A Streptomyces coelicolor. transcriptional regulator (Pip) has been adapted to modulate reporter gene expression (SEAP, secreted alkaline phosphatase) in Chinese hamster ovary cells (CHO) in response to streptogramin antibiotics. This CHO cell-based technology was more sensitive in detecting the production of the model streptogramin pristinamycin, from Streptomyces pristinaespiralis, than antibiogram tests using a variety of human pathogenic bacteria as indicator strains. The reporter system was able to detect pristinamycin compound produced by asingle S. pristinaespiralis colony. The assay was rapid (17 hours) and could be carried out in a high-throughput 96-well plate assay format or a 24-well transwell set-up. This novel mammalian cell-based antibiotic screening concept enables detection of bioavailable and non-cytotoxic representativesof a particular class of antibiotics in a single assay and represents a promising alternative to traditional antibiogram-based screening programs.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/07/20 alle ore 17:37:15