共 17 条
An inhibitor of FtsZ with potent and selective anti-staphylococcal activity
被引:389
作者:
Haydon, David J.
[1
]
Stokes, Neil R.
[1
]
Ure, Rebecca
[1
]
Galbraith, Greta
[1
]
Bennett, James M.
[1
]
Brown, David R.
[1
]
Baker, Patrick J.
[2
]
Barynin, Vladimir V.
[2
]
Rice, David W.
[2
]
Sedelnikova, Sveta E.
[2
]
Heal, Jonathan R.
[3
]
Sheridan, Joseph M.
[3
]
Aiwale, Sachin T.
[4
]
Chauhan, Pramod K.
[4
]
Srivastava, Anil
[4
]
Taneja, Amit
[4
]
Collins, Ian
[1
]
Errington, Jeff
[1
,5
]
Czaplewski, Lloyd G.
[1
]
机构:
[1] Prolysis, Oxford OX5 1PF, England
[2] Univ Sheffield, Dept Mol Biol & Biotechnol, Sheffield S10 2TN, S Yorkshire, England
[3] Prosarix, Cambridge CB22 7ZE, England
[4] Jubilant Chemsys, Noida 201301, India
[5] Univ Newcastle, Fac Med Sci, Inst Cell & Mol Biosci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England
来源:
基金:
英国生物技术与生命科学研究理事会;
英国惠康基金;
关键词:
D O I:
10.1126/science.1159961
中图分类号:
O [数理科学和化学];
P [天文学、地球科学];
Q [生物科学];
N [自然科学总论];
学科分类号:
07 ;
0710 ;
09 ;
摘要:
FtsZ is an essential bacterial guanosine triphosphatase and homolog of mammalian beta-tubulin that polymerizes and assembles into a ring to initiate cell division. We have created a class of small synthetic antibacterials, exemplified by PC190723, which inhibits FtsZ and prevents cell division. PC190723 has potent and selective in vitro bactericidal activity against staphylococci, including methicillin- and multi- drug- resistant Staphylococcus aureus. The putative inhibitor- binding site of PC190723 was mapped to a region of FtsZ that is analogous to the Taxol- binding site of tubulin. PC190723 was efficacious in an in vivo model of infection, curing mice infected with a lethal dose of S. aureus. The data validate FtsZ as a target for antibacterial intervention and identify PC190723 as suitable for optimization into a new anti- staphylococcal therapy.
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页码:1673 / 1675
页数:3
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