Antisense phosphorodiamidate morpholino oligomers targeted to an essential gene inhibit Burkholderia cepacia complex.
Antisense phosphorodiamidate morpholino oligomers targeted to an essential gene inhibit Burkholderia cepacia complex.
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DOI：
10.1086/652807
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发表时间：
2010-06-15
期刊：
影响因子：
--
通讯作者：
Geller BL
中科院分区：
文献类型：
--
作者：
Greenberg DE;Marshall-Batty KR;Brinster LR;Zarember KA;Shaw PA;Mellbye BL;Iversen PL;Holland SM;Geller BL
洋葱伯克霍尔德菌复合体（Bcc）的成员在慢性肉芽肿病（CGD）和囊性纤维化（CF）患者中引起显著的发病率和死亡率。许多Bcc菌株是抗生素抗性的，需要探索新的抗微生物方法，包括反义技术，如磷酰二胺吗啉代寡聚物（PMO）。肽缀合的PMO（PPMO）是为了靶向acpP基因而开发的，该基因编码一种被认为对生长至关重要的酰基载体蛋白。在体外和感染模型中测试了它们对不同Bcc菌株的抗菌活性。靶向acpP的PPMO对Bcc的临床分离株具有杀菌作用（> 4 log减少），而具有乱序碱基序列（Scr）的PPMO对生长没有影响。用B感染人中性粒细胞（PMN）。多噬菌体，并用AcpP PPMO处理。与单独的PMN ± Scr PPMO相比，AcpP PPMO增强了杀伤。感染B的CGD小鼠。在感染后0、3和6小时，用AcpP PPMO、Scr PPMO或水处理多噬菌体。与水处理的对照组相比，AcpP PPMO处理的小鼠显示到第30天死亡风险降低约80%，并且病理学相对较少。AcpP PPMO在体外和体内都具有抗Bcc感染的活性。
Members of the Burkholderia cepacia complex (Bcc) cause significant morbidity and mortality in patients with chronic granulomatous disease (CGD) and cystic fibrosis (CF). Many Bcc strains are antibiotic resistant requiring the exploration of novel antimicrobial approaches including antisense technologies, such as phosphorodiamidate morpholino oligomers (PMOs). Peptide-conjugated PMOs (PPMOs) were developed to target the acpP gene, encoding an acyl carrier protein thought to be essential for growth. Their antimicrobial activities were tested against different strains of Bcc in vitro and in infection models. PPMOs targeting acpP were bactericidal against clinical isolates of Bcc (> 4 log reduction), whereas a PPMO with a scrambled base sequence (Scr) had no effect on growth. Human neutrophils (PMN) were infected with B. multivorans, and treated with AcpP PPMO. AcpP PPMO augmented killing compared to PMN alone ± Scr PPMO. CGD mice infected with B. multivorans were treated with AcpP PPMO, Scr PPMO or water at 0, 3 and 6 hours post-infection. Compared to water treated controls, the AcpP PPMO treated mice showed a ~80% reduction in the risk of dying by day 30 and relatively little pathology. AcpP PPMO is active against Bcc infections in vitro and in vivo.
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DOI：
10.1016/j.jcf.2004.01.005
发表时间：
2004-06-01
期刊：
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society
影响因子：
--
作者：
Courtney, J M;Dunbar, K E A;Elborn, J S
通讯作者：
Elborn, J S
DOI：
10.1099/ijs.0.65634-0
发表时间：
2008-07-01
影响因子：
2.8
作者：
Vanlaere, Elke;LiPuma, John J.;Vandamme, Peter
通讯作者：
Vandamme, Peter
影响因子：
4.9
作者：
Tilley, Lucas D.;Hine, Orion S.;Geller, Bruce L.
通讯作者：
Geller, Bruce L.
影响因子：
1.2
作者：
Kulyté, A;Nekhotiaeva, N;Good, L
通讯作者：
Good, L
影响因子：
3.3
作者：
LiPuma, JJ
通讯作者：
LiPuma, JJ