Reverse Vaccinology Approach to Identify Novel and Immunogenic Targets against Streptococcus gordonii

Biology Pub Date : 2024-07-09 DOI:10.3390/biology13070510
Aneeqa Abid, Badr Alzahrani, S. Naz, Amina Basheer, S. Bakhtiar, Fahad Al-Asmari, Syed Babar Jamal, Muhammad Faheem
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Abstract

Streptococcus gordonii is a gram-positive, mutualistic bacterium found in the human body. It is found in the oral cavity, upper respiratory tract, and intestines, and presents a serious clinical problem because it can lead to opportunistic infections in individuals with weakened immune systems. Streptococci are the most prevalent inhabitants of oral microbial communities, and are typical oral commensals found in the human oral cavity. These streptococci, along with many other oral microbes, produce multispecies biofilms that can attach to salivary pellicle components and other oral bacteria via adhesin proteins expressed on the cell surface. Antibiotics are effective against this bacterium, but resistance against antibodies is increasing. Therefore, a more effective treatment is needed. Vaccines offer a promising method for preventing this issue. This study generated a multi-epitope vaccine against Streptococcus gordonii by targeting the completely sequenced proteomes of five strains. The vaccine targets are identified using a pangenome and subtractive proteomic approach. In the present study, 13 complete strains out of 91 strains of S. gordonii are selected. The pangenomics results revealed that out of 2835 pan genes, 1225 are core genes. Out of these 1225 core genes, 643 identified as non-homologous proteins by subtractive proteomics. A total of 20 essential proteins are predicted from non-homologous proteins. Among these 20 essential proteins, only five are identified as surface proteins. The vaccine construct is designed based on selected B- and T-cell epitopes of the antigenic proteins with the help of linkers and adjuvants. The designed vaccine is docked against TLR2. The expression of the protein is determined using in silico gene cloning. Findings concluded that Vaccine I with adjuvant shows higher interactions with TLR2, suggesting that the vaccine has the ability to induce a humoral and cell-mediated response to treat and prevent infection; this makes it promising as a vaccine against infectious diseases caused by S. gordonii. Furthermore, validation of the vaccine construct is required by in vitro and in vivo trials to check its actual potency and safety for use to prevent infectious diseases caused by S. gordonii.
用逆向疫苗学方法确定抗戈尔登链球菌的新型免疫原性靶标
戈登链球菌是一种存在于人体内的革兰氏阳性互生细菌。它存在于口腔、上呼吸道和肠道中,会给免疫力低下的人带来严重的临床问题,因为它会导致机会性感染。链球菌是口腔微生物群落中最常见的居民,也是人类口腔中典型的口腔共生菌。这些链球菌与许多其他口腔微生物一起产生多菌种生物膜,可通过细胞表面表达的粘附蛋白附着在唾液胶粒成分和其他口腔细菌上。抗生素对这种细菌有效,但抗体的抗药性却在增加。因此,需要一种更有效的治疗方法。疫苗为预防这一问题提供了一种很有前景的方法。本研究以五株菌株的完全测序蛋白质组为靶标,生成了针对戈登链球菌的多表位疫苗。疫苗靶标是通过庞基因组和减法蛋白质组方法确定的。在本研究中,从 91 株戈登氏菌中选出了 13 株完整菌株。泛基因组学结果显示,在 2835 个泛基因中,有 1225 个是核心基因。在这 1225 个核心基因中,有 643 个通过减法蛋白质组学鉴定为非同源蛋白。从非同源蛋白中共预测出 20 个必需蛋白。在这 20 个必需蛋白中,只有 5 个被鉴定为表面蛋白。在连接体和佐剂的帮助下,根据抗原蛋白的选定 B 细胞和 T 细胞表位设计了疫苗构建体。设计出的疫苗与 TLR2 对接。利用基因克隆技术确定蛋白质的表达。研究结果表明,含有佐剂的疫苗 I 与 TLR2 的相互作用较强,这表明该疫苗能够诱导体液和细胞介导的反应,从而治疗和预防感染;这使其有望成为预防由戈尔登菌引起的传染病的疫苗。此外,还需要通过体外和体内试验对疫苗构建物进行验证,以检查其用于预防由戈尔登菌引起的传染病的实际效力和安全性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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