Section of Integrative Biology, The University of Texas at Austin, Austin, TX 78712, USA.
Virology. 2010 Mar 1;398(1):79-86. doi: 10.1016/j.virol.2009.11.040. Epub 2009 Dec 16.
Prior studies treating mice infected with Escherichia coli O18:K1:H7 observed that phages requiring the K1 capsule for infection (K1-dep) were superior to capsule-independent (K1-ind) phages. We show that three K1-ind phages all have low fitness when grown on cells in serum whereas fitnesses of four K1-dep phages were high. The difference is serum-specific, as fitnesses in broth overlapped. Sialidase activity was associated with all K1-dep virions tested but no K1-ind virions, a phenotype supported by sequence analyses. Adding endosialidase to cells infected with K1-ind phage increased fitness in serum by enhancing productive infection after adsorption. We propose that virion sialidase activity is the primary determinant of high fitness on cells grown in serum, and thus in a mammalian host. Although the benefit of sialidase is specific to K1-capsulated bacteria, this study may provide a scientific rationale for selecting phages for therapeutic use in many systemic infections.
先前研究感染大肠杆菌 O18:K1:H7 的小鼠时发现，需要 K1 荚膜才能感染的噬菌体（K1 依赖型噬菌体）比不依赖荚膜的噬菌体（K1 独立型噬菌体）更优越。我们发现，当在含血清的细胞中生长时，三种 K1 独立型噬菌体的适应性都较低，而四种 K1 依赖型噬菌体的适应性都较高。这种差异是血清特异性的，因为在肉汤中的适应性重叠。唾液酸酶活性与所有测试的 K1 依赖型病毒粒子都有关，但与 K1 独立型病毒粒子无关，这一表型得到了序列分析的支持。向感染 K1 独立型噬菌体的细胞中添加内切唾液酸酶，通过增强吸附后的有效感染，提高了在血清中的适应性。我们提出，病毒粒子的唾液酸酶活性是在含血清的细胞中适应性高的主要决定因素，因此也是在哺乳动物宿主中适应性高的主要决定因素。尽管唾液酸酶的益处是特定于 K1 荚膜细菌的，但这项研究可能为选择噬菌体用于治疗许多全身性感染提供了科学依据。
