School of Biosciences, The Florey Institute, University of Sheffield, Sheffield, United Kingdom.
The Medical Research Council, The Gambia, London School of Hygiene and Tropical Medicine, Serekunda, The Gambia.
mSphere. 2023 Feb 21;8(1):e0046922. doi: 10.1128/msphere.00469-22. Epub 2022 Dec 12.
Streptococcus pyogenes is a leading cause of human morbidity and mortality, especially in resource-limited settings. The development of a vaccine against S. pyogenes is a global health priority to reduce the burden of postinfection rheumatic heart disease. To support this, molecular characterization of circulating S. pyogenes isolates is needed. We performed whole-genome analyses of S. pyogenes isolates from skin and soft tissue infections in Sukuta, The Gambia, a low-income country (LIC) in West Africa where there is a high burden of such infections. To act as a comparator to these LIC isolates, skin infection isolates from Sheffield, United Kingdom (a high-income country [HIC]), were also sequenced. The LIC isolates from The Gambia were genetically more diverse (46 types in 107 isolates) than the HIC isolates from Sheffield (23 types in 142 isolates), with only 7 overlapping types. Other molecular markers were shared, including a high prevalence of the skin infection-associated pattern D and the variable fibronectin-collagen-T antigen (FCT) types FCT-3 and FCT-4. Fewer of the Gambian LIC isolates carried prophage-associated superantigens (64%) and DNases (26%) than did the Sheffield HIC isolates (99% and 95%, respectively). We also identified streptococcin genes unique to 36% of the Gambian LIC isolates and a higher prevalence (48%) of glucuronic acid utilization pathway genes in the Gambian LIC isolates than in the Sheffield HIC isolates (26%). Comparison to a wider collection of HIC and LIC isolate genomes supported our findings of differing diversity and prevalence of bacterial factors. Our study provides insight into the genetics of LIC isolates and how they compare to HIC isolates. The global burden of rheumatic heart disease (RHD) has triggered a World Health Organization response to drive forward development of a vaccine against the causative human pathogen Streptococcus pyogenes. This burden stems primarily from low- and middle-income settings where there are high levels of S. pyogenes skin and soft tissue infections, which can lead to RHD. Our study provides much needed whole-genome-based molecular characterization of isolates causing skin infections in Sukuta, The Gambia, a low-income country (LIC) in West Africa where infection and RHD rates are high. Although we identified a greater level of diversity in these LIC isolates than in isolates from Sheffield, United Kingdom (a high-income country), there were some shared features. There were also some features that differed by geographical region, warranting further investigation into their contribution to infection. Our study has also contributed data essential for the development of a vaccine that would target geographically relevant strains.
化脓性链球菌是导致人类发病率和死亡率的主要原因，尤其是在资源有限的环境中。开发针对化脓性链球菌的疫苗是全球卫生重点，旨在减轻感染后风湿性心脏病的负担。为了支持这一目标，需要对循环化脓性链球菌分离株进行分子特征分析。我们对冈比亚苏库塔的皮肤和软组织感染的化脓性链球菌分离株进行了全基因组分析，苏库塔是西非的一个低收入国家（LIC），那里此类感染的负担很重。为了与这些 LIC 分离株进行比较，我们还对来自英国谢菲尔德（一个高收入国家[HIC]）的皮肤感染分离株进行了测序。来自冈比亚的 LIC 分离株在遗传上比来自英国谢菲尔德的 HIC 分离株更为多样化（107 株中有 46 种类型），只有 7 种重叠类型。还共享了其他分子标记物，包括高流行的皮肤感染相关模式 D 和可变纤连蛋白-胶原蛋白-T 抗原（FCT）类型 FCT-3 和 FCT-4。与谢菲尔德的 HIC 分离株相比，冈比亚的 LIC 分离株携带噬菌体相关超抗原（64%）和 DNase（26%）的比例较低（分别为 99%和 95%）。我们还发现，36%的冈比亚 LIC 分离株具有独特的链球菌素基因，而冈比亚 LIC 分离株中葡萄糖醛酸利用途径基因的流行率（48%）高于谢菲尔德 HIC 分离株（26%）。与更广泛的 HIC 和 LIC 分离株基因组的比较支持了我们的发现，即不同的多样性和细菌因子的流行率。我们的研究提供了对 LIC 分离株遗传特征的深入了解，以及它们与 HIC 分离株的比较。风湿性心脏病（RHD）的全球负担促使世界卫生组织采取行动，推动针对致病人类病原体化脓性链球菌的疫苗开发。这一负担主要源于中低收入国家，那里有很高水平的化脓性链球菌皮肤和软组织感染，这可能导致 RHD。我们的研究为冈比亚苏库塔皮肤感染分离株提供了急需的全基因组分子特征分析，苏库塔是西非的一个低收入国家（LIC），那里感染和 RHD 率很高。尽管我们在这些 LIC 分离株中发现了比英国谢菲尔德（一个高收入国家）分离株更高水平的多样性，但也有一些共同的特征。也有一些因地理位置不同而不同的特征，这需要进一步调查它们对感染的贡献。我们的研究还提供了疫苗开发的重要数据，该疫苗将针对地理相关的菌株。
