Colicin

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Background

Colicins are encoded on E. coli-derived plasmids, which can be low molecular weight, multi-copy plasmids of approximately 6 kb, containing few other genetic determinants; They can also be high molecular weight, over 40 kb single-copy plasmids carrying many additional genes that are self-delivered by coupling. Colicins are protein toxins produced by E. coli bacteria to kill related bacteria. Colicins are modular proteins with three functional domains that act together on the outside of sensitive cells, cross the OM, and translocate to sites of cytotoxic action.

Fig.1 Model of the colicin import mechanism. (Kim, 2014)

Functions of Colicin Lysis Proteins

• Colicin release

The main function of the lysin is to promote the release of colicin, so it is more accurately referred to as the colicin-releasing protein Cxr. After induction by DNA damaging agents, colistin is expressed and accumulated in the cytoplasm of producing cells. Mutations in colicin lysin have been reported to block release.

• Quasilysis

Quasilysis is a good report of colicin cleavage protein function.

• Modifications of the cell envelope structure

After colicin induction, the cell envelope structure changed.

• Activation of OmpLA, the outer membrane phospholipase A

OmpLA activation is thought to result in colicin release, quasilysis, and host cell death. It promotes the formation of lysophospholipids, a detergent that permeates the outer membrane and then the inner membrane of the cell.

• Death of the host cell
• Regulator of expression of the colicin operon

The presence of a transposon in the lys gene of colicin E8 significantly reduces colicin E8 synthesis, suggesting a role for the E8 lysin in the regulation of colicin E8 synthesis.

Mechanism of Action (MoA)

Colicins have different modes of cytotoxicity; some make ion-conducting channels in the cytoplasmic (inner) membrane (IM) of susceptible cells, thereby de-energizing those cells, whereas others enzymatically degrade RNA or DNA in the cytoplasm or peptidoglycan precursors in the periplasm. Colistin binds to specific cell surface receptors and is transported to sensitive cells. As they enter the cell, they kill by one of several mechanisms: 1) channel formation in the cytoplasmic membrane, 2) cellular DNA degradation, 3) protein biosynthesis inhibition by cleaving RNA, or 4) murein and lipopolysaccharide biosynthesis inhibition by interfering with lipid carrier regeneration.

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Reference:

1. Kim, Y.C.; et al. Colicin import into E. coli cells: a model system for insights into the import mechanisms of bacteriocins. Biochim Biophys Acta. 2014, 1843(8): 1717-31.