Abstract |
Sortase enzymes belong to a family of transpeptidases found in Gram-positive bacteria. Sortase is responsible for the reaction that anchors surface protein virulence factors to the peptidoglycan cell wall of the bacteria. The compound (Z)-3-(2,5-dimethoxyphenyl)-2-(4-methoxyphenyl) acrylonitrile ( DMMA) has previously been reported as a novel sortase inhibitor in vitro, but the in vivo effects of DMMA have not been studied. Here, we evaluated the in vivo effects of DMMA against infection by wild-type and sortase A- and/or sortase B-deficient Staphylococcus aureus in Balb/c mice. With DMMA treatment, survival rates increased and kidney and joint infection rates decreased (p<0.01) in a dose-dependent manner. The rate of kidney infection was significantly reduced in the mice treated with sortase A knock-out S. aureus (p<0.01). These results indicate that by acting as a potent inhibitor of sortase A and moderate inhibitor of sortase B, DMMA can decrease kidney and joint infection rates and reduce mortality in mice infected with S. aureus. These findings suggest that DMMA is a promising therapeutic compound against Gram-positive bacteria.
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Authors | Ki-Bong Oh, Kung-Woo Nam, Hyunjin Ahn, Jongheon Shin, Sanghee Kim, Woongchon Mar |
Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 396
Issue 2
Pg. 440-4
(May 28 2010)
ISSN: 1090-2104 [Electronic] United States |
PMID | 20433810
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright (c) 2010 Elsevier Inc. All rights reserved. |
Chemical References |
- 3-(2,5-dimethoxyphenyl)-2-(4-methoxyphenyl)acrylonitrile
- Anti-Bacterial Agents
- Bacterial Proteins
- Enzyme Inhibitors
- Stilbenes
- sortase B
- Aminoacyltransferases
- sortase A
- Cysteine Endopeptidases
- Acrylonitrile
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Topics |
- Acrylonitrile
(analogs & derivatives, therapeutic use)
- Aminoacyltransferases
(antagonists & inhibitors, genetics)
- Animals
- Anti-Bacterial Agents
(therapeutic use)
- Bacterial Proteins
(antagonists & inhibitors, genetics)
- Cysteine Endopeptidases
(genetics)
- Disease Models, Animal
- Enzyme Inhibitors
(therapeutic use)
- Female
- Joints
(microbiology)
- Kidney
(microbiology)
- Mice
- Mice, Inbred BALB C
- Staphylococcal Infections
(drug therapy)
- Staphylococcus aureus
(enzymology, genetics)
- Stilbenes
(therapeutic use)
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