Genetic Engineering of Bacteriophage K1F with Human Epidermal Growth Factor to Enhance Killing of Intracellular E. coli K1.
Genetic Engineering of Bacteriophage K1F with Human Epidermal Growth Factor to Enhance Killing of Intracellular E. coli K1.
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DOI：
10.1021/acssynbio.3c00135
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发表时间：
2023-07-21
影响因子：
4.7
通讯作者：
Sagona, Antonia P.
中科院分区：
文献类型：
--
作者：
Williams, Joshua;Kerven, Jaimee;Chen, Yin;Sagona, Antonia P.
关键词：
细菌感染是全球范围内人类发病率和死亡率的主要原因。许多细菌病原体，如大肠杆菌，可以通过细胞进入和逃避宿主免疫系统而在细胞内引起疾病。抗生素耐药性导致了这种感染的问题，这就需要开发新的抗菌剂。噬菌体是一种有效的替代品，因为它们的特异性和遗传修饰的简便性。我们已经改造了针对E.ColiK1的噬菌体K1F，它可以在次要衣壳蛋白上表达表皮生长因子(EGF)和绿色荧光蛋白(GFP)的融合。在这里，我们证明了EGF标记的噬菌体K1F可以更容易地内化到人类细胞系中，从而消除细胞内的E.ColiK1感染。此外，我们证实K1F-GFP-EGF主要通过EGF受体(EGFR)诱导后的内吞作用进入人类细胞，颠覆吞噬进入细胞的方式，并允许其在胞浆中附着以寻找其细菌宿主。
Bacterial infections are a major cause of human morbidity and mortality on a global scale. Many bacterial pathogens, such as Escherichia coli, can cause diseases intracellularly via cell entry and avoidance of the host immune system. Antibiotic resistance has caused such infections to be problematic, which has necessitated the development of new antimicrobials. Bacteriophages are a potent alternative due to their specificity and ease of genetic modification. We have engineered phage K1F, which is specific to E. coli K1 to express an epidermal growth factor (EGF) and green fluorescent protein (GFP) fusion on the minor capsid protein. Here, we demonstrate that EGF-labeled phage K1F can be internalized more readily in human cell lines to eradicate E. coli K1 infection intracellularly. Further, we establish that K1F-GFP-EGF enters human cells primarily through endocytosis following EGF receptor (EGFR) induction, subverting the phagocytic mode of entry and permitting its accretion in the cytosol to seek out its bacterial host.
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影响因子：
5.8
作者：
Bichet MC;Chin WH;Richards W;Lin YW;Avellaneda-Franco L;Hernandez CA;Oddo A;Chernyavskiy O;Hilsenstein V;Neild A;Li J;Voelcker NH;Patwa R;Barr JJ
通讯作者：
Barr JJ
影响因子：
3.4
作者：
Kim, KJ;Elliott, SJ;Kim, KS
通讯作者：
Kim, KS
影响因子：
4.2
作者：
Larocca, D;Witte, A;Baird, A
通讯作者：
Baird, A
影响因子：
3.1
作者：
Hoffman, JA;Badger, JL;Kim, KS
通讯作者：
Kim, KS
影响因子：
7.5
作者：
FUNFSTUCK, R;TSCHAPE, H;WESSEL, G
通讯作者：
WESSEL, G