志贺氏菌病,由福氏志贺氏菌诱导,在发展中国家构成了巨大的健康负担,特别影响社会经济弱势社区。被世界卫生组织(世卫组织)列为腹泻病的第二大流行原因,每年估计有21.2万人死亡。在福氏链球菌菌株的范围内,血清型X是非常普遍和有弹性的,然而,它的全面表征仍然不足。本研究致力于辨别潜在的药理学靶标,并重新利用现有的药物化合物来对抗福氏链球菌血清型X。采用消减基因组学的框架,该研究询问了福氏链球菌血清型X(菌株2,002,017;UP000001884)的参考基因组,以将其蛋白质组划分为非同源类别,非旁系,必要的,剧毒,和抗性成分,从而促进治疗目标的识别。随后,针对已确定的药物靶标,从FDA文库中筛选约9000种化合物,旨在描述对抗福氏链球菌血清型X感染的有效药物.减法基因组学方法的应用产生了预后见解,揭示非同源蛋白(n=4122),非同源物(n=1803),基本(n=1246),药物样(n=389),抗性(n=167),在参考蛋白质组中的42种毒力蛋白。该迭代过程最终鉴定了丝氨酸O-乙酰转移酶作为可行的药物靶标。随后的虚拟筛选努力发掘FDA批准的能够抑制丝氨酸O-乙酰转移酶的药用化合物。值得注意的候选人,如DB12983,DB15085,DB16098,DB16185和DB16262出现,尽管有吉祥的发现,但仍有可能减轻福氏链球菌血清型X。必须认真审查,以确定拟议候选药物相对于福氏杆菌的疗效和安全性.
Shigellosis, induced by Shigella flexneri, constitutes a significant health burden in developing nations, particularly impacting socioeconomically disadvantaged communities. Designated as the second most prevalent cause of diarrheal illness by the World Health Organization (WHO), it precipitates an estimated 212,000 fatalities annually. Within the spectrum of S. flexneri strains, serotype X is notably pervasive and resilient, yet its comprehensive characterization remains deficient. The present investigation endeavors to discern potential pharmacological targets and repurpose existing drug compounds against S. flexneri serotype X. Employing the framework of subtractive genomics, the study interrogates the reference genome of S. flexneri Serotype X (strain 2,002,017; UP000001884) to delineate its proteome into categories of non-homologous, non-paralogous, essential, virulent, and resistant constituents, thereby facilitating the identification of therapeutic targets. Subsequently, a screening of approximately 9000 compounds from the FDA library against the identified drug target aims to delineate efficacious agents for combating S. flexneri serotype X infections. The application of subtractive genomics methodology yields prognostic insights, unveiling non-paralogous proteins (n = 4122), non-homologues (n = 1803), essential (n = 1246), drug-like (n = 389), resistant (n = 167), alongside 42 virulent proteins within the reference proteome. This iterative process culminates in the identification of Serine O-acetyltransferase as a viable drug target. Subsequent virtual screening endeavors to unearth FDA-approved medicinal compounds capable of inhibiting Serine O-acetyltransferase. Noteworthy candidates such as DB12983, DB15085, DB16098, DB16185, and DB16262 emerge, exhibiting potential for mitigating S. flexneri Serotype X. Despite the auspicious findings, diligent scrutiny is imperative to ascertain the efficacy and safety profile of the proposed drug candidates vis-à-vis S. flexneri.