Small molecule inhibitor of lipoteichoic acid synthesis is an antibiotic for Gram-positive bacteria.
Proc Natl Acad Sci U S A
; 110(9): 3531-6, 2013 Feb 26.
Article
em En
| MEDLINE
| ID: mdl-23401520
ABSTRACT
The current epidemic of infections caused by antibiotic-resistant gram-positive bacteria requires the discovery of new drug targets and the development of new therapeutics. Lipoteichoic acid (LTA), a cell wall polymer of gram-positive bacteria, consists of 1,3-polyglycerol-phosphate linked to glycolipid. LTA synthase (LtaS) polymerizes polyglycerol-phosphate from phosphatidylglycerol, a reaction that is essential for the growth of gram-positive bacteria. We screened small molecule libraries for compounds inhibiting growth of Staphylococcus aureus but not of gram-negative bacteria. Compound 1771 [2-oxo-2-(5-phenyl-1,3,4-oxadiazol-2-ylamino)ethyl 2-naphtho[2,1-b]furan-1-ylacetate] blocked phosphatidylglycerol binding to LtaS and inhibited LTA synthesis in S. aureus and in Escherichia coli expressing ltaS. Compound 1771 inhibited the growth of antibiotic-resistant gram-positive bacteria and prolonged the survival of mice with lethal S. aureus challenge, validating LtaS as a target for the development of antibiotics.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Staphylococcus aureus
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Ácidos Teicoicos
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Lipopolissacarídeos
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Inibidores Enzimáticos
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Bibliotecas de Moléculas Pequenas
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Antibacterianos
Limite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos