Influenza promotes pneumococcal growth during coinfection by providing host sialylated substrates as a nutrient source.
Influenza promotes pneumococcal growth during coinfection by providing host sialylated substrates as a nutrient source.
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DOI：
10.1016/j.chom.2014.06.005
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发表时间：
2014-07-09
影响因子：
30.3
通讯作者：
Weiser JN
中科院分区：
文献类型：
--
作者：
Siegel SJ;Roche AM;Weiser JN
流感病毒导致的死亡很大程度上是由于继发性细菌性肺炎，特别是肺炎链球菌。然而，这种联合感染的潜在机制尚不完全清楚。我们发现，先前的流感感染增强了肺炎球菌在小鼠鼻咽的定植，这反过来又促进了细菌向肺部的传播。流感加速了体内细菌的复制，而唾液酸是呼吸道糖结合物的主要成分，被认为是刺激肺炎球菌增殖的宿主来源的代谢物。流感感染增加唾液酸和唾液酸化粘蛋白的可获得性，并增强宿主糖结合物的去除性。肺炎球菌的唾液酸分解代谢基因是流感促进细菌生长所必需的。通过主要呼吸道粘蛋白Muc5ac的基因缺失或粘液溶解治疗减少体内唾液酸的可获得性限制了流感诱导的肺炎球菌复制。我们的发现表明，混合感染期间较高的发病率可能源于流感提供的唾液酸，它增加了肺炎球菌的增殖、定植和吸入。
Much of the mortality attributed to influenza virus is due to secondary bacterial pneumonia, particularly from Streptococcus pneumoniae. However, mechanisms underlying this co-infection are incompletely understood. We find that prior influenza infection enhances pneumococcal colonization of the murine nasopharynx, which in-turn promotes bacterial spread to the lungs. Influenza accelerates bacterial replication in vivo, and sialic acid, a major component of airway glycoconjugates, is identified as the host-derived metabolite that stimulates pneumococcal proliferation. Influenza infection increases sialic acid and sialylated mucin availability, and enhances desialylation of host glycoconjugates. Pneumococcal genes for sialic acid catabolism are required for influenza to promote bacterial growth. Decreasing sialic acid availability in vivo by genetic deletion of the major airway mucin Muc5ac or mucolytic treatment limits influenza-induced pneumococcal replication. Our findings suggest that higher rates of disease during co-infection could stem from influenza-provided sialic acid, which increases pneumococcal proliferation, colonization and aspiration.
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