Bacteriophage uptake by mammalian cell layers represents a potential sink that may impact phage therapy.
Bacteriophage uptake by mammalian cell layers represents a potential sink that may impact phage therapy.
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DOI：
10.1016/j.isci.2021.102287
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发表时间：
2021-04-23
期刊：
影响因子：
5.8
通讯作者：
Barr JJ
中科院分区：
文献类型：
--
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
越来越明显的是，噬菌体，即感染细菌的病毒，更常见的是简称为噬菌体，在其细菌宿主之外具有趋向性。利用活组织培养细胞成像，我们证明了细胞类型、噬菌体大小和形态在噬菌体内化中起主要作用。使用微流控装置在生理条件下验证摄取。噬菌体附着在哺乳动物组织上，附着的噬菌体随后被巨噬细胞吞噬作用内化，功能性噬菌体在细胞内积累。我们将这些结果合并到一个药代动力学模型中，展示了噬菌体在细胞层积累的潜在影响，这代表了体内循环噬菌体的潜在下沉。在噬菌体治疗期间，为了治疗细菌感染，患者直接服用高剂量的噬菌体，从而促进噬菌体与哺乳动物细胞之间的广泛相互作用。了解这些相互作用将对先天免疫反应、噬菌体药代动力学和噬菌体疗法的疗效具有重要意义。活细胞成像显示噬菌体被上皮细胞内化细胞类型、噬菌体大小和形态都会影响摄取率内化噬菌体的功能和随着时间的推移在细胞内积累的药代动力学模型展示了机体免疫学、微生物学、病毒学对噬菌体积累的影响
It is increasingly apparent that bacteriophages, viruses that infect bacteria and more commonly referred to as simply phages, have tropisms outside their bacterial hosts. Using live tissue culture cell imaging, we demonstrate that cell type, phage size, and morphology play a major role in phage internalization. Uptake was validated under physiological conditions using a microfluidic device. Phages adhered to mammalian tissues, with adherent phages being subsequently internalized by macropinocytosis, with functional phages accumulating intracellularly. We incorporated these results into a pharmacokinetic model demonstrating the potential impact of phage accumulation by cell layers, which represents a potential sink for circulating phages in the body. During phage therapy, high doses of phages are directly administered to a patient in order to treat a bacterial infection, thereby facilitating broad interactions between phages and mammalian cells. Understanding these interactions will have important implications on innate immune responses, phage pharmacokinetics, and the efficacy of phage therapy. Live-cell imaging showed that bacteriophages were internalized by epithelial cells Cell type, phage size, and morphology all influenced the rate of uptake Internalized phages were functional and accumulated within cells over time A pharmacokinetic model demonstrated the impact of phage accumulation by the body Immunology; Microbiology; Virology
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DOI：
10.1073/pnas.1508355112
发表时间：
2015-11-03
影响因子：
11.1
作者：
Barr, Jeremy J.;Auro, Rita;Rohwer, Forest
通讯作者：
Rohwer, Forest
DOI：
10.1073/pnas.1305923110
发表时间：
2013-06-25
影响因子：
11.1
作者：
Barr, Jeremy J.;Auro, Rita;Rohwer, Forest
通讯作者：
Rohwer, Forest
DOI：
10.1007/bf02615323
发表时间：
1975-01-01
期刊：
IN VITRO-JOURNAL OF THE TISSUE CULTURE ASSOCIATION
影响因子：
--
作者：
GEIER, MR;ATTALLAH, AFM;MERRIL, CR
通讯作者：
MERRIL, CR
影响因子：
64.5
作者：
Handley SA;Thackray LB;Zhao G;Presti R;Miller AD;Droit L;Abbink P;Maxfield LF;Kambal A;Duan E;Stanley K;Kramer J;Macri SC;Permar SR;Schmitz JE;Mansfield K;Brenchley JM;Veazey RS;Stappenbeck TS;Wang D;Barouch DH;Virgin HW
通讯作者：
Virgin HW
影响因子：
30.3
作者：
Gogokhia, Lasha;Buhrke, Kate;Round, June L.
通讯作者：
Round, June L.