Structural and functional insights into colicin: a new paradigm in drug discovery

Colicins are agents of allelopathic interactions produced by certain enterobacteria which give them a competitive advantage in the environment. These protein molecules are mostly encoded by plasmids. The colicin operon consists of the activity, immunity and the lysis genes. The activity protein is responsible for the killing activity, the immunity protein protects the producer cell from the lethal action of colicin and the lysis protein facilitates its release. Colicins are primarily composed of three domains, namely the receptor-binding domain, the translocation domain and the cytotoxic domain. The protein molecule binds to its cognate receptor on the target cell via the receptor-binding domain and undergoes translocation into the cell either via the Tol system or the Ton system. After gaining entry into the target cell, there are various mechanisms by which colicins exert their lethality. These comprise DNase activity, RNase activity and pore formation in the target cell membrane or peptidoglycan synthesis inhibition. This review gives a detailed insight into the structural and functional aspect of colicins and their mode of action. This knowledge is of immense significance because colicins are being considered as very useful alternatives to conventional antibiotics in the treatment of multidrug-resistant infections. Besides, they also have a negligible harmful impact on the commensals. Thus, before tapping their therapeutic potential, it is imperative to know their structure and mechanism of action in detail.