Population structure of ocular Streptococcus pneumoniae is highly diverse and formed by lineages that escape current vaccines.

Population structure of ocular Streptococcus pneumoniae is highly diverse and formed by lineages that escape current vaccines.
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DOI:
10.1099/mgen.0.000763
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发表时间:
2022-03
期刊:
影响因子:
3.9
通讯作者:
Bispo, Paulo J. M.
Bispo, Paulo J. M.
中科院分区:
生物学2区
文献类型:
--
作者:
Andre, Camille;Rouhana, John;de Mello, Suelen Scarpa;da Cunha, Gabriela Rosa;Van Camp, Andrew G.;Gilmore, Michael S.;Bispo, Paulo J. M.

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肺炎链球菌是眼部感染的主要原因,包括严重和威胁视力的疾病。肺炎球菌结合疫苗(PCV)的使用大大降低了肺炎和侵袭性肺炎球菌疾病的发病率,但对眼部感染的影响有限。此外,疫苗的广泛使用造成了携带者和疾病中持续的选择压力和血清型替代。为了深入了解pcv -13后时期引起眼部感染的肺炎球菌分离株的种群结构,我们研究了2014年至2017年在马萨诸塞州眼耳收集的眼部肺炎链球菌分离株(n=45)的基因组流行病学。通过从基因组草图中进行一系列分子分型方法,我们发现眼部肺炎链球菌的群体结构高度多样化,有27个序列类型(分为18个克隆复合物)和17个血清型。根据分离地点的不同,这些谱系的分布也不同,结膜炎通常由流行结膜炎群- ecc中的分离株引起(60%),而ST448(53.3%)是最常见的。相反,肺炎链球菌角膜炎病例是由15种不同克隆复合体中高度多样化的分离菌群引起的。血清分型推断显示95.5%的分离株为非pcv -13疫苗型。大多数结膜炎分离株(80%)未包封,其余为15B、3和23B血清型。另一方面,引起角膜炎的肺炎链球菌主要为包膜型(95.2%),共鉴定出13种不同的血清型,主要为非疫苗型。大环内酯类耐药基因在我们的眼部肺炎链球菌群体中很常见(42.2%),通常与mefA +msrD基因型相关(n=15)。这些基因位于大环内酯外排遗传组装盒中,与14和15元大环内酯的低水平体外抗性有关。大环内酯耐药菌株携带ermB基因(n=4),该基因与tn -916样转座子中的tetM基因位于同一位置。我们的研究表明,眼部肺炎链球菌的种群结构高度多样化,主要由逃避PCV-13疫苗的分离株组成,具有组织/生态位分离、适应和特化模式。这些发现表明,眼部肺炎球菌的种群结构可能受到多种因素的影响,包括PCV-13选择压力、微生物相关和小生境特异性宿主相关特征。
Streptococcus pneumoniae is a leading cause of ocular infections including serious and sight-threatening conditions. The use of pneumococcal conjugate vaccines (PCV) has substantially reduced the incidence of pneumonia and invasive pneumococcal diseases, but has had limited impact on ocular infections. Additionally, widespread vaccine use has resulted in ongoing selective pressure and serotype replacement in carriage and disease. To gain insight into the population structure of pneumococcal isolates causing ocular infections in a post-PCV-13 time period, we investigated the genomic epidemiology of ocular S. pneumoniae isolates (n=45) collected at Massachusetts Eye and Ear between 2014 and 2017. By performing a series of molecular typing methods from draft genomes, we found that the population structure of ocular S. pneumoniae is highly diverse with 27 sequence types (grouped into 18 clonal complexes) and 17 serotypes being identified. Distribution of these lineages diverged according to the site of isolation, with conjunctivitis being commonly caused by isolates grouped in the Epidemic Conjunctivitis Cluster-ECC (60 %), and ST448 (53.3 %) being most frequently identified. Conversely, S. pneumoniae keratitis cases were caused by a highly diverse population of isolates grouping within 15 different clonal complexes. Serotyping inference demonstrated that 95.5 % of the isolates were non-PCV-13 vaccine types. Most of the conjunctivitis isolates (80 %) were unencapsulated, with the remaining belonging to serotypes 15B, 3 and 23B. On the other hand, S. pneumoniae causing keratitis were predominantly encapsulated (95.2 %) with 13 different serotypes identified, mostly being non-vaccine types. Carriage of macrolide resistance genes was common in our ocular S. pneumoniae population (42.2 %), and usually associated with the mefA +msrD genotype (n=15). These genes were located in the Macrolide Efflux Genetic Assembly cassette and were associated with low-level in vitro resistance to 14- and 15-membered macrolides. Less frequently, macrolide-resistant isolates carried an ermB gene (n=4), which was co-located with the tetM gene in a Tn-916-like transposon. Our study demonstrates that the population structure of ocular S. pneumoniae is highly diverse, mainly composed by isolates that escape the PCV-13 vaccine, with patterns of tissue/niche segregation, adaptation and specialization. These findings suggest that the population structure of ocular pneumococcus may be shaped by multiple factors including PCV-13 selective pressure, microbial-related and niche-specific host-associated features.
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