Streptococcus pneumoniae infection can lead to pneumococcal disease, a major cause of mortality in children under the age of five years. In low- and middle-income country settings where pneumococcal disease burden is high, vaccine use is low and widespread antibiotic use has led to increased rates of multi-drug resistant pneumococci. l-sulforaphane (LSF), derived from broccoli and other cruciferous vegetables, has established anti-inflammatory, antioxidant, and anti-microbial properties. Hence, we sought to investigate the potential role of LSF against pneumococcal infection. Using a combination of in vitro and computational methods, the results showed that LSF and relevant metabolites had a potential to reduce pneumococcal adherence through modulation of host receptors, regulation of inflammation, or through direct modification of bacterial factors. Treatment with LSF and metabolites reduced pneumococcal adherence to respiratory epithelial cells. Synchrotron-Fourier transform infrared microspectroscopy (S-FTIR) revealed biochemical changes in protein and lipid profiles of lung epithelial cells following treatment with LSF or metabolites. Molecular docking studies of 116 pneumococcal and 89 host factors revealed a potent effect for the metabolite LSF-glutathione (GSH). A comprehensive list of factors involved in interactions between S. pneumoniae and host cells was compiled to construct a bacterium and host interaction network. Network analysis revealed plasminogen, fibronectin, and RrgA as key factors involved in pneumococcal-host interactions. Therefore, we propose that these constitute critical targets for direct inhibition by LSF and/or metabolites, which may disrupt pneumococcal-host adherence. Overall, our findings further enhance understanding of the potential role of LSF to modulate pneumococcal-host dynamics.

肺炎链球菌感染可导致肺炎球菌疾病，这是5岁以下儿童死亡的主要原因。在肺炎球菌疾病负担高的中低收入国家，疫苗使用率低，抗生素的广泛使用已导致耐多种药物的肺炎球菌发生率上升。源自西兰花和其他十字花科蔬菜的l-萝卜硫素（LSF）具有抗炎，抗氧化和抗微生物的特性。因此，我们试图研究LSF对肺炎球菌感染的潜在作用。结合使用体外和计算方法，结果表明LSF和相关代谢产物具有通过调节宿主受体，调节炎症或通过直接修饰细菌因子来减少肺炎球菌粘附的潜力。用LSF和代谢物治疗可减少肺炎球菌对呼吸道上皮细胞的粘附。同步加速器-傅立叶变换红外光谱（S-FTIR）显示，经LSF或代谢物处理后，肺上皮细胞蛋白质和脂质谱的生化变化。对116个肺炎球菌和89个宿主因子的分子对接研究表明，该代谢物对LSF-谷胱甘肽（GSH）具有有效作用。肺炎链球菌相互作用中涉及因素的综合清单并编译宿主细胞以构建细菌和宿主相互作用网络。网络分析表明，纤溶酶原，纤连蛋白和RrgA是参与肺炎球菌与宿主相互作用的关键因素。因此，我们建议这些构成直接抑制LSF和/或代谢物的关键靶标，这可能会破坏肺炎球菌宿主的粘附。总体而言，我们的发现进一步增强了对LSF调节肺炎球菌宿主动态的潜在作用的了解。