Global emergence and population dynamics of divergent serotype 3 CC180 pneumococci.
Global emergence and population dynamics of divergent serotype 3 CC180 pneumococci.
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DOI：
10.1371/journal.ppat.1007438
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发表时间：
2018-11
期刊：
影响因子：
6.7
通讯作者：
Hanage WP
中科院分区：
文献类型：
--
作者：
Azarian T;Mitchell PK;Georgieva M;Thompson CM;Ghouila A;Pollard AJ;von Gottberg A;du Plessis M;Antonio M;Kwambana-Adams BA;Clarke SC;Everett D;Cornick J;Sadowy E;Hryniewicz W;Skoczynska A;Moïsi JC;McGee L;Beall B;Metcalf BJ;Breiman RF;Ho PL;Reid R;O'Brien KL;Gladstone RA;Bentley SD;Hanage WP
尽管包括在13价肺炎球菌结合疫苗(PCV13)中，3型肺炎链球菌仍然是全球发病率和死亡率的重要原因。自美国实施PCV13以来，血清3型携带率增加，而侵袭性疾病发生率保持不变。我们通过对荷兰3-31(PMEN31)克隆CC180的301株3型血清分离株的全球样本的基因组分析，结合相关的患者数据和分离株收集国家之间的PCV利用情况，调查了3型血清在携带者和疾病中的持久性。我们评估了被膜电荷(Zeta电位)、被膜多糖脱落和对吞噬细胞杀伤的易感性的优势分支之间的表型差异，这之前已经与携带持续时间、侵袭性和疫苗逃逸相关。我们发现CC180人群最近的转变归因于一种名为Clade II的世系，贝叶斯合并分析估计这种世系最早出现在1968年[95%HPD：1939-1989]，此后患病率和有效人口规模都有所增加。分支II分离株在非囊膜抗原组成、活性和对抗生素的敏感性上与PCV13前的3型分离株不同，后者是由于获得了一个Tn916样的接合转座子造成的。不同分支之间重组率的差异与CLP蛋白酶的ATP结合亚单位的变化以及comCDE操纵子中的氨基酸替换有关。吞噬细胞杀伤试验阐明了PCV13对3型血清的低观察到的有效性。PCV13在被抽样国家之间的使用差异与CC180种群转移没有独立的相关性；因此，蛋白质抗原的基因型和表型差异，特别是抗生素耐药性，可能是导致Clade II增加的原因。我们的分析强调需要从分散的地理地区，包括历史上采样不足的地区对分离株进行常规、代表性的抽样。我们还强调了基因组学在解决血清型内的抗原性和流行病学变异方面的价值，这可能对未来的疫苗开发有影响。肺炎链球菌是细菌性肺炎、脑膜炎和中耳炎的主要原因。尽管3型包括在最新的肺炎球菌结合疫苗PCV13中，但在全球范围内仍具有重要的流行病学意义。我们使用1993-2014年间从24个国家收集的301个分离物的全基因组测序数据来调查3型血清的持久性。通过系统发育分析，我们在一个克隆复合体CC180中鉴定了三个不同的谱系，并发现了最近出现并流行的一个。然后，我们比较了不同谱系之间的基因组差异，以及不同样本国家之间肺炎球菌疫苗使用的差异。我们发现，最近出现的被称为Clade II的谱系比其他谱系具有更高的抗生素耐药性患病率，不同的表面蛋白抗原，以及更高的重组率，这是一个细菌可以吸收和整合来自周围环境的遗传物质的过程。样本国家之间疫苗使用的差异似乎与Clade II的出现无关。我们强调了对来自不同地理区域的细菌分离株进行常规、有代表性的采样的必要性，并展示了基因组数据在解决病原体种群内流行病学差异方面的效用。
Streptococcus pneumoniae serotype 3 remains a significant cause of morbidity and mortality worldwide, despite inclusion in the 13-valent pneumococcal conjugate vaccine (PCV13). Serotype 3 increased in carriage since the implementation of PCV13 in the USA, while invasive disease rates remain unchanged. We investigated the persistence of serotype 3 in carriage and disease, through genomic analyses of a global sample of 301 serotype 3 isolates of the Netherlands3–31 (PMEN31) clone CC180, combined with associated patient data and PCV utilization among countries of isolate collection. We assessed phenotypic variation between dominant clades in capsule charge (zeta potential), capsular polysaccharide shedding, and susceptibility to opsonophagocytic killing, which have previously been associated with carriage duration, invasiveness, and vaccine escape. We identified a recent shift in the CC180 population attributed to a lineage termed Clade II, which was estimated by Bayesian coalescent analysis to have first appeared in 1968 [95% HPD: 1939–1989] and increased in prevalence and effective population size thereafter. Clade II isolates are divergent from the pre-PCV13 serotype 3 population in non-capsular antigenic composition, competence, and antibiotic susceptibility, the last of which resulting from the acquisition of a Tn916-like conjugative transposon. Differences in recombination rates among clades correlated with variations in the ATP-binding subunit of Clp protease, as well as amino acid substitutions in the comCDE operon. Opsonophagocytic killing assays elucidated the low observed efficacy of PCV13 against serotype 3. Variation in PCV13 use among sampled countries was not independently correlated with the CC180 population shift; therefore, genotypic and phenotypic differences in protein antigens and, in particular, antibiotic resistance may have contributed to the increase of Clade II. Our analysis emphasizes the need for routine, representative sampling of isolates from disperse geographic regions, including historically under-sampled areas. We also highlight the value of genomics in resolving antigenic and epidemiological variations within a serotype, which may have implications for future vaccine development. Streptococcus pneumoniae is a leading cause of bacterial pneumoniae, meningitis, and otitis media. Despite its inclusion in the most recent pneumococcal conjugate vaccine, PCV13, serotype 3 remains epidemiologically important globally. We investigated the persistence of serotype 3 using whole-genome sequencing data from 301 isolates collected among 24 countries from 1993–2014. Through phylogenetic analysis, we identified three distinct lineages within a single clonal complex, CC180, and found one that has recently emerged and grown in prevalence. We then compared genomic difference among lineages as well as variations in pneumococcal vaccine use among sampled countries. We found that the recently emerged lineage, termed Clade II, has a higher prevalence of antibiotic resistance compared to other lineages, diverse surface protein antigens, and a higher rate of recombination, a process by which bacteria can uptake and incorporate genetic material from its surroundings. Differences in vaccine use among sampled countries did not appear to be associated with the emergence of Clade II. We highlight the need for routine, representative sampling of bacterial isolates from diverse geographic areas and show the utility of genomic data in resolving epidemiological differences within a pathogen population.
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影响因子：
4.2
作者：
Camilli R;Bonnal RJ;Del Grosso M;Iacono M;Corti G;Rizzi E;Marchetti M;Mulas L;Iannelli F;Superti F;Oggioni MR;De Bellis G;Pantosti A
通讯作者：
Pantosti A
影响因子：
3.1
作者：
BRILES, DE;CRAIN, MJ;YOTHER, J
通讯作者：
YOTHER, J
影响因子：
--
作者：
Daniels, Calvin C.;Kim, Kyung-Hyo;Briles, David E.
通讯作者：
Briles, David E.
影响因子：
11.8
作者：
Dagan, Ron;Patterson, Scott;Scott, Daniel A.
通讯作者：
Scott, Daniel A.
影响因子：
10.7
作者：
Bobay LM;Rocha EP;Touchon M
通讯作者：
Touchon M