Viral Coinfection Replaces Effects of Suilysin on Streptococcus suis Adherence to and Invasion of Respiratory Epithelial Cells Grown under Air-Liquid Interface Conditions
Viral Coinfection Replaces Effects of Suilysin on Streptococcus suis Adherence to and Invasion of Respiratory Epithelial Cells Grown under Air-Liquid Interface Conditions
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DOI：
10.1128/iai.00350-19
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发表时间：
2019-08-01
影响因子：
3.1
通讯作者：
Valentin-Weigand, Peter
中科院分区：
文献类型：
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作者：
Meng, Fandan;Tong, Jie;Valentin-Weigand, Peter
猪链球菌是一种重要的人畜共患病病原体，可在全球范围内感染人和猪，对全球公共卫生构成潜在威胁。猪链球菌溶血素是一种成孔的胆固醇依赖性细胞溶血素，在猪链球菌感染的发病机制中起重要作用。众所周知，感染甲型流感病毒可能更容易发生继发性细菌感染，导致更严重的疾病和更高的死亡率。然而，这些联合感染背后的分子机制还不完全清楚。利用在气液界面(ALI)条件下培养的高分化猪呼吸道上皮细胞，分析了猪流感病毒(SIV)对猪链球菌毒力的贡献，特别是其溶细胞毒素Suilysin。我们发现，在继发性细菌感染过程中，猪链球菌的溶血素在感染早期对分化良好的呼吸道上皮细胞造成了损伤，而在感染后期，SIV诱导的细胞毒作用变得更加明显。先前被SIV感染的猪以唾液酸依赖的方式增加了野生型(Wt)猪链球菌株和猪速溶素阴性链球菌突变体对猪呼吸道上皮细胞的黏附和定植。在细菌侵袭方面，观察到了显著的差异。在细菌单一感染后，只有猪链球菌菌株表现出侵袭性表型，而突变体仍保持粘附性。当上皮细胞预先感染SIV时，溶血素阴性突变株也表现出侵袭能力。因此，我们认为，与SIV共感染可能弥补了溶血素阴性猪链球菌在黏附和侵袭过程中缺乏溶血素的情况。
Streptococcus suis is an important zoonotic pathogen which can infect humans and pigs worldwide, posing a potential risk to global public health. Suilysin, a pore-forming cholesterol-dependent cytolysin, is considered to play an important role in the pathogenesis of S. suis infections. It is known that infection with influenza A viruses may favor susceptibility to secondary bacterial infection, resulting in more severe disease and increased mortality. However, the molecular mechanisms underlying these coinfections are incompletely understood. Applying highly differentiated primary porcine respiratory epithelial cells grown under air-liquid interface (ALI) conditions, we analyzed the contribution of swine influenza viruses (SIV) to the virulence of S. suis, with a special focus on its cytolytic toxin, suilysin. We found that during secondary bacterial infection, suilysin of S. suis contributed to the damage of well-differentiated respiratory epithelial cells in the early stage of infection, whereas the cytotoxic effects induced by SIV became prominent at later stages of infection. Prior infection by SIV enhanced the adherence to and colonization of porcine airway epithelial cells by a wild-type (wt) S. suis strain and a suilysin-negative S. suis mutant in a sialic acid-dependent manner. A striking difference was observed with respect to bacterial invasion. After bacterial monoinfection, only the wt S. suis strain showed an invasive phenotype, whereas the mutant remained adherent. When the epithelial cells were preinfected with SIV, the suilysin-negative mutant also showed an invasion capacity. Therefore, we propose that coinfection with SIV may compensate for the lack of suilysin in the adherence and invasion process of suilysin-negative S. suis.