Transition of Serotype 35B Pneumococci From Commensal to Prevalent Virulent Strain in Children.
Transition of Serotype 35B Pneumococci From Commensal to Prevalent Virulent Strain in Children.
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DOI：
10.3389/fcimb.2021.744742
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发表时间：
2021
影响因子：
5.7
通讯作者：
Kaur R
中科院分区：
文献类型：
--
作者：
Fuji N;Pichichero M;Ehrlich RL;Mell JC;Ehrlich GD;Kaur R
在我们对幼儿进行的基于社区的前瞻性队列研究中，我们观察到2011-2014年期间肺炎球菌血清型35 B鼻咽（NP）细菌定植显著增加，但这些菌株与疾病无关。从2015年开始并持续到现在，血清型35 B毒力发生了变化，它成为我们队列中分离出的与肺炎球菌急性中耳炎（AOM）相关的主要细菌。我们对从2006年至2019年收集的140名儿童中获得的250株35 B分离株进行了比较分析。分析了患病率、克隆复合体组成和抗生素耐药性的变化。72个（29%）的35 B分离株进行全基因组测序，以调查与毒力变化相关的基因组变化，导致35 B相关AOM疾病的发病率增加。35株B型菌株主要与序列型（ST）558相关，其中35株B型菌株主要与序列型（ST）558相关。抑制35 B菌株生长所需的β-内酰胺类和氧氟沙星抗生素浓度显著上升（2006-2019年）（p<0.005）。然而，在2006-2014年和2015-2019年期间，只有来自35 B/ST 558的分离株显示青霉素和氧氟沙星的MIC 50显著增加（p=0.007和p<0.0001）。位于34个不同基因的138个SNP与2015年后的菌株显著相关。SNPs见于nrdG（金属结合，10%）; metP和metN（ABC转运蛋白，9%）; corA（Mg 2+转运蛋白，6%）; priA（DNA复制，5%）;和酶基因ldcB（LD-羧肽酶，3%）。肺炎球菌血清型35 B菌株是2010-2014年期间常见的NP菌株。2015年，由35 B引起的幼儿AOM病例数量增加，这与遗传组成和抗生素敏感性的变化有关。
In our community-based prospective cohort study in young children, we observed a significant increase in pneumococcal serotype 35B nasopharyngeal (NP) commensal colonization during the 2011–2014 timeframe, but these strains were not associated with disease. Beginning in 2015 and continuing through to the present, the serotype 35B virulence changed, and it became the dominant bacteria isolated and associated with pneumococcal acute otitis-media (AOM) in our cohort. We performed comparative analyses of 250 35B isolates obtained from 140 children collected between 2006 and 2019. Changes in prevalence, clonal-complex composition, and antibiotic resistance were analyzed. Seventy-two (29%) of 35B isolates underwent whole-genome sequencing to investigate genomic changes associated with the shift in virulence that resulted in increased rates of 35B-associated AOM disease. 35B strains that were commensals and AOM disease-causing were mainly associated with sequence type (ST) 558. Antibiotic concentrations of β-lactams and ofloxacin necessary to inhibit growth of 35B strains rose significantly (2006–2019) (p<0.005). However, only isolates from the 35B/ST558 showed significant increases in MIC50 of penicillin and ofloxacin between the years 2006–2014 and 2015–2019 (p=0.007 and p<0.0001). One hundred thirty-eight SNPs located in 34 different genes were significantly associated with post-2015 strains. SNPs were found in nrdG (metal binding, 10%); metP and metN (ABC transporter, 9%); corA (Mg2+ transporter, 6%); priA (DNA replication, 5%); and on the enzymic gene ldcB (LD-carboxypeptidase, 3%). Pneumococcal serotype 35B strains was a common NP commensal during 2010–2014. In 2015, a shift in increasing number of AOM cases occurred in young children caused by 35B, that was associated with changes in genetic composition and antibiotic susceptibility.