公开(公告)号：US07838502B2

公开(公告)日：2010-11-23

申请号：US11123761

申请日：2005-05-06

申请人： Brian J. Akerley ,  Sandy M. Wong

发明人： Brian J. Akerley ,  Sandy M. Wong

IPC分类号： A01N43/04

CPC分类号： A61K39/102 ,  A61K2039/522

摘要： The present invention discloses novel signaling pathways controlling the pathogenesis of the human respiratory bacterium, Haemophilus influenzae. The lipooligosaccharide-phosphorylycholine (LOS-PC) cell surface epitope of H. influenzae enhances pathogenesis but also increases bacterial susceptibility to innate and adaptive immunity and the administration of therapeutic compounds. Modulation of the LOS-PC epitope may be affected by an interaction between environmental conditions (i.e., for example, oxygen tension) and genetic regulation of precursor biosynthetic pathway activity. LOS-PC epitope display increases under microaerobic conditions and decreases under aerobic conditions. This is consisent with a bacteria's propensity to initiate pathogensis under low oxygen conditions. Pathogenesis may be prevented by disrupting the role of the putative H. influenzae homologue of CsrA, that downregulates galU expression. Disrupting CsrA repression of galU expression resulted in increased LOS-PC epitope display.

摘要翻译： 本发明公开了控制人呼吸道细菌，流感嗜血杆菌发病机理的新型信号通路。 流感嗜血杆菌的脂寡糖 - 磷酰胆碱（LOS-PC）细胞表面表位增强发病机制，但也增加了对先天免疫和适应性免疫的治疗化合物的细菌易感性。 LOS-PC表位的调节可能受环境条件（例如，氧气张力）和前体生物合成途径活性的遗传调控之间的相互作用的影响。 LOS-PC表位显示在微需氧条件下增加，在需氧条件下降低。 这与细菌在低氧条件下启动病原体的倾向是一致的。 可以通过破坏推定的流感嗜血杆菌同源物CsrA的作用来阻止发病机制，其下调galU表达。 破坏CsrA抑制galU表达导致增加的LOS-PC表位显示。

公开(公告)号：US06368830B1

公开(公告)日：2002-04-09

申请号：US09671950

申请日：2000-09-27

申请人： David J. Lampe ,  Hugh M. Robertson ,  Eric J. Rubin ,  Brian J. Akerley

发明人： David J. Lampe ,  Hugh M. Robertson ,  Eric J. Rubin ,  Brian J. Akerley

IPC分类号： C12N1574

CPC分类号： C12N9/22 ,  C12N15/74

摘要： Mariner-family transposable elements are active in a wide variety of organisms and are becoming increasingly important genetic tools in species lacking sophisticated genetics. The Himar1 element, a member of the mariner family, isolated from the horn fly, Haematobia irritans, is active in Escherichia coli when expressed appropriately. Using this fact, a genetic screen was devised to isolate hyperactive mutants of Himar1 transposase that enhance overall transposition from 4 to 50-fold as measured in an E. coli assay. These hyperactive Himar1 mutant transposases should enable sophisticated analysis of the biochemistry of mariner transposition and should improve efficiency of a variety of genetic manipulations involving transposition in vivo and in vitro such as random mutagenesis or transgenesis in a wide range of host cells than the transposable elements previously available.

摘要翻译： 水手家族转座因子在各种生物体中是活跃的，并且在缺乏复杂遗传学的物种中变得越来越重要的遗传工具。 Himar1元素，海员家族的成员，从角飞，哈马氏杆菌分离，在适当表达时在大肠杆菌中活跃。 使用这个事实，设计了一种遗传筛选来分离Himar1转座酶的活性突变体，其将整体转座增加4倍至50倍，如在大肠杆菌测定中所测定的。 这些超活跃的Himar1突变体转座酶应该能够复杂地分析海员转座的生物化学，并且应该提高涉及体内和体外转座的各种遗传操作的效率，例如在广泛的宿主细胞中的随机诱变或转基因，而不是以前的转座元件 可用。

公开(公告)号：US06207384B1

公开(公告)日：2001-03-27

申请号：US09277565

申请日：1999-03-26

申请人： John J. Mekalanos ,  Brian J. Akerley ,  Eric J. Rubin ,  Andrew Camilli

发明人： John J. Mekalanos ,  Brian J. Akerley ,  Eric J. Rubin ,  Andrew Camilli

IPC分类号： C12Q102

CPC分类号： C12N15/1082 ,  C12N15/102 ,  C12N15/1034 ,  C12Q1/6811 ,  Y02A50/52

摘要： The invention features a general system for the identification of essential genes in organisms. This system is applicable to the discovery of novel target genes for antimicrobial compounds, as well as to the discovery of genes that enhance cell growth or viability.

摘要翻译： 本发明具有用于鉴定生物体中必需基因的一般系统。 该系统适用于发现抗微生物化合物的新型靶基因，以及发现增强细胞生长或活力的基因。