Screening Systems for Detecting Inhibitors of Cell Wall Transglycosylation in Enterococcus: Cell Wall Transglycosylation Inhibitors in Enterococcus

We devised two screening systems to detect cell wall transglycosylation inhibitors. One screen utilizes a mutant of Enterococcus faecalis strain A256 that is dependent on vancomycin or moenomycin for growth. In the absence of transglycosylation inhibitors the strain fails to grow, while in the prese...

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Bibliographic Details
Published in:Journal of antibiotics 1998/05/25, Vol.51(5), pp.471-479
Main Authors: MANI, NAGRAJ, SANCHET, PRAVEEN, JIANG, ZHI-DONG, MCNANEY, COLLEEN, DECENZO, MAUREEN, KNIGHTI, BEN, STANKIS, MARY, KURANDA, MIKE, ROTHSTEIN, DAVID M.
Format: Article
Language:English
Subjects:
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Base Sequence
Biological and medical sciences
Cell Wall - drug effects
Enterococcus faecalis - drug effects
Fermentation
Glycosylation
Hydroxybenzoates - chemistry
Hydroxybenzoates - pharmacology
Medical sciences
Microbial Sensitivity Tests
Molecular Structure
Oligodeoxyribonucleotides
Pharmacology. Drug treatments
Vancomycin - pharmacology
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Summary:We devised two screening systems to detect cell wall transglycosylation inhibitors. One screen utilizes a mutant of Enterococcus faecalis strain A256 that is dependent on vancomycin or moenomycin for growth. In the absence of transglycosylation inhibitors the strain fails to grow, while in the presence of inhibitors, cells are rescued. A second screening organism E. faecalis strain MDD212 utilizes a translational fusion of the lacZ gene to the vanH promoter in a derivative of E. faecalis that contains a vancomycin resistance determinant. Induction of β-galactosidase occurs when cells are exposed to inhibitors of transglycosylation. Our natural products drug source of fungal fermentations was tested with these screens. Several cultures that produced the same family of compounds, called the thielavins, were detected. Thielavin B inhibited the formation of peptidoglycan in an in vitro assay, suggesting that these screening systems can detect compounds that interfere with cell wall transglycosylation.
ISSN:0021-8820
1881-1469
DOI:10.7164/antibiotics.51.471