High levels of recombination among Streptococcus pneumoniae isolates from the Gambia.
High levels of recombination among Streptococcus pneumoniae isolates from the Gambia.
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作者：
Donkor ES;Bishop CJ;Gould K;Hinds J;Antonio M;Wren B;Hanage WP
我们对从冈比亚上游省<24个月的儿童中收集的148株肺炎球菌携带分离株进行了多位点序列分型（MLST）。MLST揭示了一个多样化的人口。共发现76种不同的序列类型（ST），其中最常见的是802和919，分别与23 F和6A血清型相关。与MLST数据库的比较表明，目前样本中发现的ST中只有11种在非洲以外报告。6例ST显示有囊膜转换的证据（172、802、847、1730、1736和1737）。血清型开关证实微阵列检测胶囊基因。通过使用微阵列分析的分离物中，40/69（58%）含有tetM抗性决定子。检测重组的统计遗传分析发现，49/144（34%）分离株显示出显著（P < 0.05）的混合证据，这比在来自英国（5%）和芬兰（2%）的类似样本中观察到的要高。我们推测，大量的混合物可能反映了该地区多重携带的高流行率，导致菌株之间同源重组的机会更多。这可能对结合疫苗接种的群体应答产生影响。在撒哈拉以南非洲的肺炎球菌的人口结构几乎没有研究，尽管在这个地区的肺炎球菌疾病的发病率和死亡率高。我们报告了迄今为止在撒哈拉以南非洲进行测序（多位点序列分型[MLST]）和微阵列分析的最大样本。结果清楚地表明，该人群与美国和欧洲的其他研究人群高度不同。此外，与发达国家的样本相比，该人群中有很高比例的分离株显示出同源重组的历史，这种重组将遗传信息改组成新的组合，并可能产生耐药性和疫苗逃逸菌株。这很可能对冈比亚和其他国家正在进行的针对肺炎球菌血清型子集的结合疫苗接种的肺炎球菌群体的进化反应产生重要影响。
We carried out multilocus sequence typing (MLST) on 148 pneumococcal carriage isolates collected from children <24 months old in the Upper River Division, the Gambia. MLST revealed a diverse population. Seventy-six different sequence types (STs) were found, the most common of which were 802 and 919, associated with 23F and 6A serotypes, respectively. Comparison with the MLST database showed that only 11 of the STs found in the present sample had been reported outside Africa. Six STs showed evidence of capsular switching (172, 802, 847, 1730, 1736, and 1737). Serotype switches were confirmed by microarrays that detected capsule genes. Of isolates analyzed by using microarrays, 40/69 (58%) harbored the tetM resistance determinant. A statistical genetic analysis to detect recombination found that 49/144 (34%) isolates showed significant (P < 0.05) evidence of admixture, which is greater than that observed in similar samples from the United Kingdom (5%) and Finland (2%). We hypothesize that large amounts of admixture could reflect the high prevalence of multiple carriage in this region, leading to more opportunities for homologous recombination between strains. This could have consequences for the population response to conjugate vaccination. The population structure of the pneumococcus in sub-Saharan Africa has barely been studied despite the high levels of morbidity and mortality due to pneumococcal disease in this region. We report the largest sample to date from carriage in sub-Saharan Africa to be typed by sequencing (multilocus sequence typing [MLST]) and microarray analysis. The results clearly show that the population is highly distinct and divergent from others studied in the United States and Europe. Moreover, in contrast with samples from developed countries, the population contains a high proportion of isolates showing a history of homologous recombination, which shuffles genetic information into new combinations and can generate drug-resistant and vaccine escape strains. This is likely to have important consequences for the evolutionary response of the pneumococcal population to conjugate vaccination targeting a subset of pneumococcal serotypes, which is under way in the Gambia and other countries.