Wren John T, Blevins Lance K, Pang Bing, Basu Roy Ankita, Oliver Melissa B, Reimche Jennifer L, Wozniak Jessie E, Alexander-Miller Martha A, Swords W Edward
Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Infect Immun. 2017 Mar 23;85(4). doi: 10.1128/IAI.01044-16. Print 2017 Apr.
Even in the vaccine era, (the pneumococcus) remains a leading cause of otitis media, a significant public health burden, in large part because of the high prevalence of nasal colonization with the pneumococcus in children. The primary pneumococcal neuraminidase, NanA, which is a sialidase that catalyzes the cleavage of terminal sialic acids from host glycoconjugates, is involved in both of these processes. Coinfection with influenza A virus, which also expresses a neuraminidase, exacerbates nasal colonization and disease by , in part via the synergistic contributions of the viral neuraminidase. The specific role of its pneumococcal counterpart, NanA, in this interaction, however, is less well understood. We demonstrate in a mouse model that NanA-deficient pneumococci are impaired in their ability to cause both nasal colonization and middle ear infection. Coinfection with neuraminidase-expressing influenza virus and potentiates both colonization and infection but not to wild-type levels, suggesting an intrinsic role of NanA. Using models, we show that while NanA contributes to both epithelial adherence and biofilm viability, its effect on the latter is actually independent of its sialidase activity. These data indicate that NanA contributes both enzymatically and nonenzymatically to pneumococcal pathogenesis and, as such, suggest that it is not a redundant bystander during coinfection with influenza A virus. Rather, its expression is required for the full synergism between these two pathogens.
即使在疫苗时代，（肺炎球菌）仍是中耳炎的主要病因，这是一个重大的公共卫生负担，很大程度上是因为儿童中肺炎球菌鼻腔定植的高发生率。主要的肺炎球菌神经氨酸酶NanA是一种唾液酸酶，可催化从宿主糖缀合物上切割末端唾液酸，它参与了这两个过程。甲型流感病毒也表达一种神经氨酸酶，与之共感染会加剧鼻腔定植和疾病，部分原因是通过病毒神经氨酸酶的协同作用。然而，其肺炎球菌对应物NanA在这种相互作用中的具体作用尚不太清楚。我们在小鼠模型中证明，缺乏NanA的肺炎球菌在引起鼻腔定植和中耳感染的能力上受损。与表达神经氨酸酶的流感病毒共感染会增强定植和感染，但达不到野生型水平，这表明NanA具有内在作用。使用模型，我们表明虽然NanA有助于上皮黏附以及生物膜活力，但它对后者的影响实际上与其唾液酸酶活性无关。这些数据表明，NanA在酶促和非酶促方面都对肺炎球菌致病机制有贡献，因此表明它在与甲型流感病毒共感染期间不是一个多余的旁观者。相反，这两种病原体之间的完全协同作用需要它的表达。
