Genome sequence of E. coli O104:H4 leads to rapid development of a targeted antimicrobial agent against this emerging pathogen.

Genome sequence of E. coli O104:H4 leads to rapid development of a targeted antimicrobial agent against this emerging pathogen.
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DOI:
10.1371/journal.pone.0033637
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Mandrell R
Mandrell R
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Scholl D;Gebhart D;Williams SR;Bates A;Mandrell R

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最近在德国发生的大肠杆菌O 104:H4的大范围爆发表明了新出现和重新出现的食源性病原体的动态性质,特别是STECs和相关致病性大肠杆菌。杆菌快速基因组测序和这些来自德国爆发菌株的数据的公开可用性使我们能够识别基因组中编码的O抗原特异性噬菌体尾刺蛋白。我们合成了这个基因,并将其融合到R型绿脓菌素的尾纤维基因,一种噬菌体尾样细菌素,并表达了新的细菌素,使得尾纤维融合物被纳入细菌素结构。所得颗粒具有特异性抗大肠杆菌的杀菌活性。大肠杆菌菌株产生O 104脂多糖抗原,包括爆发菌株。这种0-抗原尾刺-R-型绿脓菌素策略提供了一个平台,以在病原体的基因组序列可用时快速响应新出现的病原体。
A recent widespread outbreak of Escherichia coli O104:H4 in Germany demonstrates the dynamic nature of emerging and re-emerging food-borne pathogens, particularly STECs and related pathogenic E. coli. Rapid genome sequencing and public availability of these data from the German outbreak strain allowed us to identify an O-antigen-specific bacteriophage tail spike protein encoded in the genome. We synthesized this gene and fused it to the tail fiber gene of an R-type pyocin, a phage tail-like bacteriocin, and expressed the novel bacteriocin such that the tail fiber fusion was incorporated into the bacteriocin structure. The resulting particles have bactericidal activity specifically against E. coli strains that produce the O104 lipopolysaccharide antigen, including the outbreak strain. This O-antigen tailspike-R-type pyocin strategy provides a platform to respond rapidly to emerging pathogens upon the availability of the pathogen's genome sequence.
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