We employed an integrative strategy to present subtractive and comparative metabolic and genomic-based findings of therapeutic targets against Streptococcus parauberis. For the first time, we not only identified potential targets based on genomic and proteomic database analyses but also recommend a new antimicrobial drug for the treatment of olive flounder (Paralichthys olivaceus) infected with S. parauberis. To do that, 102 total annotated metabolic pathways of this bacterial strain were extracted from computational comparative metabolic and genomic databases. Six druggable proteins were identified from these metabolic pathways from the DrugBank database with their respective genes as mtnN, penA, pbp2, murB, murA, coaA, and fni out of 112 essential nonhomologous proteins. Among these hits, 26 transmembrane proteins and 77 cytoplasmic proteins were extracted as potential vaccines and drug targets, respectively. From the FDA DrugBank, ceftiofur was selected to prevent antibiotic resistance as it inhibited our selected identified target. Florfenicol is used for treatment of S. parauberis infection in flounder and was chosen as a comparator drug. All tested strains of fish isolates with S. parauberis were susceptible to ceftiofur and florfenicol with minimum inhibitory concentrations (MIC) of 0.0039–1 μg/mL and 0.5–8 μg/mL, IC₅₀ of 0.001–0.5 μg/mL and 0.7–2.7 μg/mL, and minimum biofilm eradication concentrations (MBEC) of 2–256 μg/mL and 4–64 μg/mL, respectively. Similar susceptibility profiles for ceftiofur and florfenicol were found, with ceftiofur observed as an effective and potent antimicrobial drug against both planktonic and biofilm-forming strains of the fish pathogen Streptococcus parauberis, and it can be applied in the aquaculture industry. Thus, our predictive approach not only showed novel therapeutic agents but also indicated that marketed drugs should also be tested for efficacy against newly identified targets of this important fish pathogen.

中文翻译：

---

通过从比目鱼、牙鲆分离的副乳房链球菌的基因组和蛋白质组学方法选择头孢噻呋的药效学。


我们采用综合策略来呈现针对副乳房链球菌治疗靶点的减法和比较代谢和基因组研究结果。我们首次不仅根据基因组和蛋白质组数据库分析确定了潜在靶标，还推荐了一种新的抗菌药物来治疗感染副乳房链球菌的橄榄鲽（ Paralichthys olivaceus ）。为此，从计算比较代谢和基因组数据库中提取了该细菌菌株的 102 条注释代谢途径。从 DrugBank 数据库的这些代谢途径中鉴定出 6 种可成药的蛋白质，它们各自的基因为 mtnN、penA、pbp2、 murB 、 mur A、coaA 和 fni（来自 112 种必需非同源蛋白质）。在这些命中中，分别提取了 26 个跨膜蛋白和 77 个细胞质蛋白作为潜在的疫苗和药物靶点。从 FDA DrugBank 中，选择头孢噻呋来预防抗生素耐药性，因为它抑制了我们选择的已确定靶点。氟苯尼考用于治疗比目鱼的副乳房链球菌感染，并被选为对照药物。所有测试的副乳房链球菌鱼类分离株均对头孢噻呋和氟苯尼考敏感，最低抑菌浓度 (MIC) 为 0.0039–1 μ g/mL 和 0.5–8 μ g/mL，IC ₅₀为 0.001–0.5 μ g/mL和 0.7-2.7 μg /mL，最小生物膜根除浓度 (MBEC) 分别为 2-256 μg /mL 和 4-64 μg /mL。 发现头孢噻呋和氟苯尼考具有相似的敏感性，头孢噻呋被认为是一种有效且强效的抗菌药物，可对抗鱼类病原体副乳房链球菌的浮游菌株和生物膜形成菌株，并且可应用于水产养殖业。因此，我们的预测方法不仅展示了新的治疗药物，而且还表明还应该测试市售药物针对这种重要鱼类病原体新确定的靶点的功效。