Domenech Arnau, Moreno Javier, Ardanuy Carmen, Liñares Josefina, de la Campa Adela G, Martin-Galiano Antonio J
Servicio de Microbiología, Hospital Universitari de Bellvitge, Universitat de Barcelona, IDIBELLBarcelona, Spain; CIBER de Enfermedades RespiratoriasMadrid, Spain.
Bacterial Genetics, Centro Nacional de Microbiología, Instituto de Salud Carlos IIIMajadahonda, Spain; Presidencia, Consejo Superior de Investigaciones CientíficasMadrid, Spain.
Front Microbiol. 2016 Mar 31;7:420. doi: 10.3389/fmicb.2016.00420. eCollection 2016.
The diverse pneumococcal diseases are associated with different pneumococcal lineages, or clonal complexes. Nevertheless, intra-clonal genomic variability, which influences pathogenicity, has been reported for surface virulence factors. These factors constitute the communication interface between the pathogen and its host and their corresponding genes are subjected to strong selective pressures affecting functionality and immunogenicity. First, the presence and allelic dispersion of 97 outer protein families were screened in 19 complete pneumococcal genomes. Seventeen families were deemed variable and were then examined in 216 draft genomes. This procedure allowed the generation of binary vectors with 17 positions and the classification of strains into surfotypes. They represent the outer protein subsets with the highest inter-strain discriminative power. A total of 116 non-redundant surfotypes were identified. Those sharing a critical number of common protein features were hierarchically clustered into 18 surfogroups. Most clonal complexes with comparable epidemiological characteristics belonged to the same or similar surfogroups. However, the very large CC156 clonal complex was dispersed over several surfogroups. In order to establish a relationship between surfogroup and pathogenicity, the surfotypes of 95 clinical isolates with different serogroup/serotype combinations were analyzed. We found a significant correlation between surfogroup and type of pathogenic behavior (primary invasive, opportunistic invasive, and non-invasive). We conclude that the virulent behavior of S. pneumoniae is related to the activity of collections of, rather than individual, surface virulence factors. Since surfotypes evolve faster than MLSTs and directly reflect virulence potential, this novel typing protocol is appropriate for the identification of emerging clones.
多种肺炎球菌疾病与不同的肺炎球菌谱系或克隆复合体相关。然而，已有报道称表面毒力因子存在影响致病性的克隆内基因组变异性。这些因子构成了病原体与其宿主之间的通讯界面，它们相应的基因受到影响功能和免疫原性的强大选择压力。首先，在19个完整的肺炎球菌基因组中筛选了97个外蛋白家族的存在和等位基因分散情况。17个家族被认为是可变的，然后在216个草图基因组中进行检查。这个过程允许生成具有17个位置的二元载体，并将菌株分类为表面型。它们代表了菌株间鉴别力最高的外蛋白子集。总共鉴定出116种非冗余表面型。那些共享关键数量共同蛋白特征的表面型被分层聚类为18个表面型组。大多数具有可比流行病学特征的克隆复合体属于相同或相似的表面型组。然而，非常大的CC156克隆复合体分散在几个表面型组中。为了建立表面型组与致病性之间的关系，分析了95株具有不同血清群/血清型组合的临床分离株的表面型。我们发现表面型组与致病行为类型（原发性侵袭性、机会性侵袭性和非侵袭性）之间存在显著相关性。我们得出结论，肺炎链球菌的致病行为与表面毒力因子集合而非单个因子的活性有关。由于表面型的进化速度比多位点序列分型（MLST）快，并且直接反映毒力潜力，这种新的分型方案适用于鉴定新兴克隆。
