Abstract
Clostridium perfringens is an anaerobic pathogen known to cause vast number of diseases in mammals and birds. Various toxins and hydrolysing enzymes released by the organism are responsible for the necrosis of soft tissues. Due to serious safety issues associated with current vaccines against C. perfringens, there is a need for new drug or vaccine targets. C. perfringens is extremely dependent on its host for nutrition which can be targeted for vaccine development or drug design. Therefore, it is of interest to identify the unique transport systems used by C. perfringens involved in uptake of essential amino acids that are synthesized by the host, so that therapeutic agents can be designed to target the specific transport systems. Use of bioinformatics tools resulted in the identification of a protein component of the glutamate transport system that is not present in the host. Analysis of the conservation profile of the protein domain indicated it to be a glutamate binding protein which also stimulates the ATPase activity of ATP Binding Cassettes (ABC) transporters. Homology modelling of the protein showed two distinct lobes, which is a characteristic of substrate binding proteins. This suggests that the carboxylates of glutamate might be stabilized by electrostatic interactions with basic residues as is observed with other binding proteins. Hence, the homology model of this potential drug target can be employed for in silico docking studies by suitable inhibitors.
Highlights
The genus Clostridium comprises of over 150 different species of Gram positive, spore-forming, anaerobic rod shaped bacteria belonging to the fermicutes
An additional tier of specificity can be introduced by exploiting the essential amino acids required for bacterial growth for which mammalian host cells lack ATP Binding Cassettes (ABC) import systems
A comparison of nonessential/essential amino acids need of humans and C. perfringens was carried out to identify the target transporter system for an amino acid which is essential for the pathogen and non-essential for the human host Table 1
Summary
The genus Clostridium comprises of over 150 different species of Gram positive, spore-forming, anaerobic rod shaped bacteria belonging to the fermicutes. Pathogenic species for humans and animals primarily include Clostridium perfringens, Clostridium botulinum, Clostridium difficile and C. tetani. C. perfringens is responsible for various diseases; some of the major ones are food poisoning, wound and surgical infections that lead to gas gangrene, and severe uterine infections [1]. C. perfringens produces various toxins - alpha, beta, iota, epsilon and theta. Each type of toxin is associated with a specific disease [2]. Vaccination offers a promising defence against the disease. Conventional vaccines are usually toxoid based and have several inherent issues. The toxoid-based vaccines contain significant amounts of undesirable proteins that often generate inflammatory response in the host. It would be beneficial to find drug targets or vaccine candidates that target the Clostridium species itself instead of the toxins that are produced by the organism
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