In Vivo Growth Rates Are Poorly Correlated with Phage Therapy Success in a Mouse Infection Model
In Vivo Growth Rates Are Poorly Correlated with Phage Therapy Success in a Mouse Infection Model
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DOI：
10.1128/aac.05842-11
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发表时间：
2012-02-01
影响因子：
4.9
通讯作者：
Molineux, I. J.
中科院分区：
文献类型：
--
作者：
Bull, J. J.;Otto, G.;Molineux, I. J.
在实验性感染大肠杆菌O 18：K1：H7菌株的小鼠中，两类大肠杆菌产生了截然不同的恢复水平。需要K1胶囊进行感染的噬菌体（K1-dep）拯救了几乎所有感染的小鼠，而不需要胶囊的噬菌体（K1-ind）拯救了中等数量的小鼠（类似于30%）。为了拯救受感染的小鼠，K1-ind疫苗需要比K1-dep疫苗高至少10（6）倍的接种物。然而，它们的体内生长动力学仅略微劣于K1-dep噬菌体的生长动力学，并且在同一小鼠中两种噬菌体类型之间的竞争仅揭示了K1-dep噬菌体的轻微生长优势。体内生长速率似乎不太可能是噬菌体治疗成功的主要决定因素。另一种解释是，K1-dep的成功主要是由于它们的蛋白质组组成。它们编码一种降解K1荚膜的酶，在其他工作中已经证明，这种酶足以在完全不存在病毒的情况下治愈感染。
Two classes of phages yield profoundly different levels of recovery in mice experimentally infected with an Escherichia coli O18:K1:H7 strain. Phages requiring the K1 capsule for infection (K1-dep) rescue virtually all infected mice, whereas phages not requiring the capsule (K1-ind) rescue modest numbers (similar to 30%). To rescue infected mice, K1-ind phages require at least a 10(6)-fold-higher inoculum than K1-dep phages. Yet their in vivo growth dynamics are only modestly inferior to those of K1-dep phages, and competition between the two phage types in the same mouse reveals only a slight growth advantage for the K1-dep phage. The in vivo growth rate seems unlikely to be the primary determinant of phage therapy success. An alternative explanation is that the success of K1-dep phages is due substantially to their proteomic composition. They encode an enzyme that degrades the K1 capsule, which has been shown in other work to be sufficient to cure infection in the complete absence of phages.