Bacterial genome-wide association study of hyper-virulent pneumococcal serotype 1 identifies genetic variation associated with neurotropism.
Bacterial genome-wide association study of hyper-virulent pneumococcal serotype 1 identifies genetic variation associated with neurotropism.
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DOI：
10.1038/s42003-020-01290-9
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发表时间：
2020-10-08
影响因子：
5.9
通讯作者：
Bentley SD
中科院分区：
文献类型：
--
作者：
Chaguza C;Yang M;Cornick JE;du Plessis M;Gladstone RA;Kwambana-Adams BA;Lo SW;Ebruke C;Tonkin-Hill G;Peno C;Senghore M;Obaro SK;Ousmane S;Pluschke G;Collard JM;Sigaùque B;French N;Klugman KP;Heyderman RS;McGee L;Antonio M;Breiman RF;von Gottberg A;Everett DB;Kadioglu A;Bentley SD
超毒力肺炎链球菌血清1型菌株在撒哈拉以南非洲流行，经常导致致命的脑膜炎爆发。目前尚不清楚血清1型菌株的遗传变异是否调节了对脑脊液的嗜性，从而导致中枢神经系统（CNS）感染，特别是脑膜炎。在这里，我们解决这个问题，通过一个大规模的线性混合模型全基因组关联研究909非洲肺炎球菌血清1型从中枢神经系统和非中枢神经系统的人类样本收集的分离株。通过控制宿主年龄、地理和菌株种群结构，我们确定了全基因组范围内表面暴露胆碱结合蛋白（P = 5.00 × 10−08）和解旋酶蛋白（P = 1.32 × 10−06）的基因型-表型相关性，这些蛋白对侵袭、免疫逃避和肺炎球菌对CNS的嗜性至关重要。小的效应量和可忽略的遗传性表明，CNS感染的病因需要多种遗传和其他因素，反映了复杂和多基因病因。我们的研究结果表明，某些病原体的遗传变异调节肺炎球菌的生存和嗜中枢神经系统组织，因此，脑膜炎的毒力。Chaguza等人使用全基因组关联研究方法，鉴定了与肺炎链球菌感染相关的显著基因型-表型关联。这些发现表明病原体的遗传变异归因于肺炎球菌嗜性中枢神经系统组织，与脑膜炎毒力的影响。
Hyper-virulent Streptococcus pneumoniae serotype 1 strains are endemic in Sub-Saharan Africa and frequently cause lethal meningitis outbreaks. It remains unknown whether genetic variation in serotype 1 strains modulates tropism into cerebrospinal fluid to cause central nervous system (CNS) infections, particularly meningitis. Here, we address this question through a large-scale linear mixed model genome-wide association study of 909 African pneumococcal serotype 1 isolates collected from CNS and non-CNS human samples. By controlling for host age, geography, and strain population structure, we identify genome-wide statistically significant genotype-phenotype associations in surface-exposed choline-binding (P = 5.00 × 10−08) and helicase proteins (P = 1.32 × 10−06) important for invasion, immune evasion and pneumococcal tropism to CNS. The small effect sizes and negligible heritability indicated that causation of CNS infection requires multiple genetic and other factors reflecting a complex and polygenic aetiology. Our findings suggest that certain pathogen genetic variation modulate pneumococcal survival and tropism to CNS tissue, and therefore, virulence for meningitis. Using a genome-wide association study approach, Chaguza et al. identify significant genotype-phenotype associations relevant to Streptococcus pneumoniae infection. These findings indicate genetic variations in the pathogen attributed to pneumococcal tropism to central nervous system tissues, with implications for meningitis virulence.
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影响因子：
5.4
作者：
Akache, Bassel;Grimm, Dirk;Kay, Mark A.
通讯作者：
Kay, Mark A.
影响因子：
6.7
作者：
Alhamdi Y;Neill DR;Abrams ST;Malak HA;Yahya R;Barrett-Jolley R;Wang G;Kadioglu A;Toh CH
通讯作者：
Toh CH
影响因子：
4.5
作者：
Chewapreecha C;Marttinen P;Croucher NJ;Salter SJ;Harris SR;Mather AE;Hanage WP;Goldblatt D;Nosten FH;Turner C;Turner P;Bentley SD;Parkhill J
通讯作者：
Parkhill J
影响因子：
9.4
作者：
du Plessis M;Allam M;Tempia S;Wolter N;de Gouveia L;von Mollendorf C;Jolley KA;Mbelle N;Wadula J;Cornick JE;Everett DB;McGee L;Breiman RF;Gladstone RA;Bentley SD;Klugman KP;von Gottberg A
通讯作者：
von Gottberg A
影响因子：
11.8
作者：
Cremers, Amelieke J. H.;Mobegi, Fredrick M.;de Jonge, Marien I.
通讯作者：
de Jonge, Marien I.