Sempere Julio, de Miguel Sara, González-Camacho Fernando, Yuste José, Domenech Mirian
Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.
Servicio de Epidemiología de la Comunidad de Madrid, Dirección General de Salud Pública, Madrid, Spain.
Front Microbiol. 2020 Feb 27;11:309. doi: 10.3389/fmicb.2020.00309. eCollection 2020.
is the main bacterial cause of respiratory infections in children and the elderly worldwide. Serotype replacement is a frequent phenomenon after the introduction of conjugated vaccines, with emerging serotypes 22F and 33F as frequent non-PCV13 serotypes in children and adults in North America and other countries. Characterization of mechanisms involved in evasion of the host immune response by these serotypes is of great importance in public health because they are included in the future conjugated vaccines PCV15 and PCV20. One of the main strategies of to persistently colonize and causes infection is biofilm formation. In this study, we have evaluated the influence of capsule polysaccharide in biofilm formation and immune evasion by using clinical isolates from different sources and isogenic strains with capsules from prevalent serotypes. Since the introduction of PCV13 in Spain in the year 2010, isolates of serotypes 22F and 33F are rising among risk populations. The predominant circulating genotypes are ST433 and ST717 , being CC433 in 22F and CC717 in 33F the main clonal complexes in Spain. The use of clinical isolates of different origin, demonstrated that pediatric isolates of serotypes 22F and 33F formed better biofilms than adult isolates and this was statistically significant. This phenotype was greater in clinical isolates from blood origin compared to those from cerebrospinal fluid, pleural fluid and otitis. Opsonophagocytosis assays showed that serotype 22F and 33F were recognized by the PSGL-1 receptor on leukocytes, although serotype 22F, was more resistant than serotype 33F to phagocytosis killing and more lethal in a mouse sepsis model. Overall, the emergence of additional PCV15 serotypes, especially 22F, could be associated to an enhanced ability to divert the host immune response that markedly increased in a biofilm state. Our findings demonstrate that pediatric isolates of 22F and 33F, that form better biofilm than isolates from adults, could have an advantage to colonize the nasopharynx of children and therefore, be important in carriage and subsequent dissemination to the elderly. The increased ability of serotype 22F to avoid the host immune response, might explain the emergence of this serotype in the last years.
是全球儿童和老年人呼吸道感染的主要细菌病因。引入结合疫苗后血清型替换是一种常见现象，在北美和其他国家，新出现的血清型22F和33F是儿童和成人中常见的非PCV13血清型。了解这些血清型逃避宿主免疫反应的机制对于公共卫生至关重要，因为它们被纳入了未来的结合疫苗PCV15和PCV20。持续定植并引发感染的主要策略之一是生物膜形成。在本研究中，我们通过使用来自不同来源的临床分离株以及具有流行血清型荚膜的同基因菌株，评估了荚膜多糖对生物膜形成和免疫逃避的影响。自2010年西班牙引入PCV13以来，血清型22F和33F的分离株在高危人群中呈上升趋势。主要的循环基因型是ST433和ST717，在西班牙，22F中的CC433和33F中的CC717是主要的克隆复合体。使用不同来源的临床分离株表明，血清型22F和33F的儿科分离株比成人分离株形成更好的生物膜，且具有统计学意义。与来自脑脊液、胸水和中耳炎的临床分离株相比，来自血液的临床分离株的这种表型更明显。调理吞噬试验表明，血清型22F和33F可被白细胞上的PSGL-1受体识别，尽管血清型22F比血清型33F对吞噬杀伤更具抗性，并且在小鼠败血症模型中更具致死性。总体而言，额外的PCV15血清型，尤其是22F的出现，可能与转移宿主免疫反应的能力增强有关，这种能力在生物膜状态下显著增加。我们的研究结果表明，血清型22F和33F的儿科分离株比成人分离株形成更好的生物膜，可能在定植儿童鼻咽部方面具有优势，因此在携带以及随后传播给老年人方面具有重要意义。血清型22F逃避宿主免疫反应的能力增强，可能解释了该血清型在过去几年中的出现。
