Therapeutic effect of (Z)-3-(2,5-dimethoxyphenyl)-2-(4-methoxyphenyl) acrylonitrile (DMMA) against Staphylococcus aureus infection in a murine model.
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.
Oh
Ki-Bong
KB
Department of Agricultural Biotechnology, College of Agriculture & Life Science, Seoul National University, Seoul 151-921, Republic of Korea.
Nam
Kung-Woo
KW
Ahn
Hyunjin
H
Shin
Jongheon
J
Kim
Sanghee
S
Mar
Woongchon
W
D000181:Acrylonitrile / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019881:Aminoacyltransferases / Q000037:antagonists & inhibitors* / Q000235:genetics; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D003546:Cysteine Endopeptidases / Q000235:genetics; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D007596:Joints / Q000382:microbiology; D007668:Kidney / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013211:Staphylococcus aureus / Q000201:enzymology* / Q000235:genetics; D013267:Stilbenes / Q000627:therapeutic use*
C550554:3-(2,5-dimethoxyphenyl)-2-(4-methoxyphenyl)acrylonitrile; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D013267:Stilbenes; C509821:sortase B; D019881:Aminoacyltransferases; C120542:sortase A; D003546:Cysteine Endopeptidases; D000181:Acrylonitrile