Boby Naila, Abbas Muhammad Aleem, Lee Eon-Bee, Park Seung-Chun
Laboratory of Veterinary Pharmacokinetics and Pharmacodynamics, College of Veterinary Medicine, Kyungpook National University, Daegu 41569, Republic of Korea.
Int J Genomics. 2020 Mar 31;2020:4850290. doi: 10.1155/2020/4850290. eCollection 2020.
We employed an integrative strategy to present subtractive and comparative metabolic and genomic-based findings of therapeutic targets against . 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 () infected with . 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, , A, 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 infection in flounder and was chosen as a comparator drug. All tested strains of fish isolates with were susceptible to ceftiofur and florfenicol with minimum inhibitory concentrations (MIC) of 0.0039-1 g/mL and 0.5-8 g/mL, IC of 0.001-0.5 g/mL and 0.7-2.7 g/mL, and minimum biofilm eradication concentrations (MBEC) of 2-256 g/mL and 4-64 g/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 , 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.
我们采用了一种综合策略来呈现针对……的基于代谢和基因组的治疗靶点的消减和比较研究结果。首次不仅基于基因组和蛋白质组数据库分析确定了潜在靶点,还推荐了一种新的抗菌药物用于治疗感染……的牙鲆。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条总注释代谢途径。从这些代谢途径中,通过DrugBank数据库鉴定出6种可成药蛋白,其各自的基因分别为mtnN、penA、pbp2、……、A、coaA和fni,来自112种必需的非同源蛋白。在这些命中结果中,分别提取了26种跨膜蛋白和77种细胞质蛋白作为潜在疫苗和药物靶点。从美国食品药品监督管理局(FDA)的DrugBank中,选择头孢噻呋以预防抗生素耐药性,因为它能抑制我们选定的已鉴定靶点。氟苯尼考用于治疗牙鲆的……感染,并被选为对照药物。所有测试的感染……的鱼类分离株对头孢噻呋和氟苯尼考均敏感,其最低抑菌浓度(MIC)分别为0.0039 - 1μg/mL和0.5 - 8μg/mL,抑菌浓度(IC)分别为0.001 - 0.5μg/mL和0.7 - 2.7μg/mL,最低生物膜清除浓度(MBEC)分别为2 - 256μg/mL和4 - 64μg/mL。发现头孢噻呋和氟苯尼考具有相似的敏感性特征,头孢噻呋被观察到是一种针对鱼类病原体……的浮游菌和生物膜形成菌株均有效的强效抗菌药物,可应用于水产养殖业。因此,我们的预测方法不仅展示了新型治疗药物,还表明市售药物也应针对这种重要鱼类病原体的新鉴定靶点进行疗效测试。