Identification of potential drug targets and vaccine candidates in Clostridium botulinum using subtractive genomics approach

利用减法基因组学方法鉴定肉毒梭菌中的潜在药物靶点和疫苗候选物

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Abstract

A subtractive genomic approach has been utilized for the identification of potential drug targets and vaccine candidates in Clostridium botulinum, the causative agent of flaccid paralysis in humans. The emergence of drug-resistant pathogenic strains has become a significant global public health threat. Treatment with antitoxin can target the neurotoxin at the extracellular level, however, can't converse the paralysis caused by botulism. Therefore, identification of drug targets and vaccine candidates in C. botulinum would be crucial to overcome drug resistance to existing antibiotic therapy. A total of 1729 crucial proteins, including chokepoint, virulence, plasmid and resistance proteins were mined and used for subtractive channel of analysis. This analysis disclosed 15 potential targets, which were non-similar to human, gut micro flora, and anti-targets in the host. The cellular localization of 6 targets was observed in the cytoplasm and might be used as a drug target, whereas 9 targets were localized in extracellular and membrane bound proteins and can be used as vaccine candidates. Furthermore, 4 targets were observed to be homologous to more than 75 pathogens and hence are considered as broad-spectrum antibiotic targets. The identified drug and vaccine targets in this study would be useful in the design and discovery of novel therapeutic compounds against botulism.

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