Position of O-Acetylation within the Capsular Repeat Unit Impacts the Biological Properties of Pneumococcal Serotypes 33A and 33F
Position of O-Acetylation within the Capsular Repeat Unit Impacts the Biological Properties of Pneumococcal Serotypes 33A and 33F
复制标题
DOI：
10.1128/iai.00132-17
复制
发表时间：
2017-07-01
影响因子：
3.1
通讯作者：
Nahm, Moon H.
中科院分区：
文献类型：
--
作者：
Spencer, Brady L.;Saad, Jamil S.;Nahm, Moon H.
肺炎链球菌（肺炎球菌）产生许多不同类型的胶囊，它们逃避宿主免疫识别的能力不同。为了解释这些血清型依赖的保护能力，许多研究已经研究了胶囊厚度或胶囊与补体蛋白的相互作用，但尚未研究胶囊的小化学修饰对其功能的影响。在肺炎球菌胶囊中经常发现的一个小的化学修饰是o -乙酰化。肺炎球菌血清型33A有两个膜结合的o -乙酰转移酶基因，wciG和wcjE。一种33A型wce缺陷变体，即33F，自然发生，随着广泛使用结合疫苗而日益流行，但没有wcg缺陷变体的报道。为了研究o -乙酰化缺失的生物学后果，我们在33a和33F两种血清型中创建了wcg缺陷变体，我们将其命名为33X1 （Delta wciG）和33X2 (Delta wciG) Delta wcjE。血清型33X1和33X2根据血清学和生化分析表达新的胶囊类型。我们发现，wcje介导的o -乙酰化缺失似乎不影响细胞壁屏蔽，因为血清型33A和33F表现出类似的非特异性抗噬细胞杀伤、生物膜生成和对鼻咽细胞的粘附，尽管血清型33F比血清型33A在短期干燥中存活得更好。然而，在血清型33X1和33X2中，wcg介导的o -乙酰化缺失导致的表型与未被包裹的菌株相似：细胞壁可达性增加，非特异性调节噬细胞杀伤增加，生物膜形成增强，对鼻咽细胞的粘附增加。我们得出结论，wcg介导的o -乙酰化对33A保护性胶囊的产生很重要，而wcye介导的o -乙酰化对胶囊的微小化学变化会极大地影响其生物学特性。
Streptococcus pneumoniae (pneumococcus) produces many capsule types that differ in their abilities to evade host immune recognition. To explain these serotype-dependent protective capacities, many studies have investigated capsular thickness or the interaction of the capsule with complement proteins, but the effects of small chemical modifications of the capsule on its function have not been studied. One small chemical modification found frequently among pneumococcal capsules is O-acetylation. Pneumococcal serotype 33A has two membrane-bound O-acetyltransferase genes, wciG and wcjE. A 33A wcjE-deficient variant, 33F, occurs naturally and is increasing in prevalence in the wake of widespread conjugate vaccine use, but no wciG-deficient variants have been reported. To study the biological consequence of the loss of O-acetylation, we created wciG-deficient variants in both serotypes33A and 33F, which we named 33X1 (Delta wciG) and 33X2 (Delta wciG Delta wcjE). Serotypes 33X1 and 33X2 express novel capsule types based on serological and biochemical analyses. We found that loss of WcjE-mediated O-acetylation appears not to affect cell wall shielding, since serotypes 33A and 33F exhibit comparable nonspecific opsonophagocytic killing, biofilm production, and adhesion to nasopharyngeal cells, though serotype 33F survived short-term drying better than serotype 33A. Loss of WciG-mediated O-acetylation in serotypes 33X1 and 33X2, however, resulted in a phenotype resembling that of nonencapsulated strains: increased cell wall accessibility, increased nonspecific opsonophagocytic killing, enhanced biofilm formation, and increased adhesion to nasopharyngeal cells. We conclude that WciG-mediated, but not WcjE-mediated, O-acetylation is important for producing protective capsules in 33A and that small chemical changes to the capsule can drastically affect its biological properties.