Bacteriocin diversity: ecological and evolutionary perspectives

Abstract

The bacteriocin family is the most abundant and diverse group of bacterial defense systems. Bacteriocins range from the well-studied narrow spectrum, high molecular weight colicins produced by Escherichia coli and the short polypeptide lantibiotics of lactic acid bacteria to the relatively unknown halocins produced almost universally by the haolobacteria. The abundance and diversity of this potent arsenal of weapons is clear. Less clear is their evolutionary origins and the role they play in mediating microbial interactions. The goal of this review is to explore what we know about the evolution and ecology of the best-characterized family of bacteriocins, the colicins. We summarize current knowledge of how such extraordinary protein diversity arose and is maintained in microbial populations and what role these toxins play in mediating microbial population-level and community-level dynamics.

Introduction

Bacteriocins are loosely defined as biologically active protein moieties with a bacteriocidal mode of action 〚1〛, 〚2〛. The family includes a diversity of proteins in terms of size, microbial targets, modes of action and immunity mechanisms. They differ from traditional antibiotics in one critical way; they have a relatively narrow killing spectrum and are only toxic to bacteria closely related to the producing strain. These toxins have been found in all major lineages of Bacteria, and within a species tens or even hundreds of different kinds of bacteriocins are produced 〚2〛, 〚3〛. According to Klaenhammer, 99% of all bacteria may make at least one bacteriocin and the only reason more have not been isolated is that very few researchers have looked for them 〚4〛. It is clear that microbes invest considerable energy into the production and elaboration of these antimicrobial mechanisms. Less clear is how such diversity arose and what roles these biological weapons serve in microbial communities.

One family of bacteriocins, the colicins, has successfully served as a model for exploring such evolutionary and ecological questions. In this review, current knowledge of how the extraordinary range of colicin diversity arose and is maintained in microbial populations will be assessed and the role these toxins play in mediating microbial dynamics will be discussed.

The most extensively studied bacteriocins, the colicins produced by Escherichia coli, share certain key characteristics 〚5〛, 〚6〛, 〚7〛, 〚8〛, 〚9〛, 〚10〛, 〚11〛. Colicin gene clusters are encoded on plasmids and are comprised of a colicin gene, which encodes the toxin, an immunity gene, which encodes a protein conferring specific immunity to the producer cell, and a lysis gene, which encodes a protein involved in colicin release from the cell. Colicin production is mediated by the SOS regulon, and is therefore, principally produced under times of stress. Toxin production is lethal for the producing cell and any neighboring cells recognized by that colicin. A receptor domain in the colicin protein that binds a specific cell surface receptor determines target recognition. This mode of targeting results in the relatively narrow phylogenetic killing range often cited for bacteriocins. The killing functions range from pore formation in the cell membrane to nuclease activity against DNA, rRNA and tRNA targets. Colicins, indeed all bacteriocins produced by Gram-negative bacteria, are large proteins. Pore forming colicins range in size from 449 to 629 amino acids. Nuclease bacteriocins have an even broader size range, from 178 to 777 amino acids.

Although colicins are representatives of Gram-negative bacteriocins, there are intriguing differences found within this subgroup of the bacteriocin family. E. coli encodes its colicins exclusively on plasmid replicons 〚12〛. The nuclease pyocins of Pseudomonas aeruginosa, which share a recent ancestry with colicins, and other, as yet uncharacterized, bacteriocins are found exclusively on the chromosome 〚13〛. Another close relative to the colicin family, the bacteriocins of Serratia marcesens are found on both plasmids and chromosomes 〚14〛, 〚15〛, 〚16〛.

Many bacteriocins isolated from Gram-negative bacteria appear to have been created by recombination between existing bacteriocins 〚6〛, 〚17〛, 〚18〛, 〚19〛. Such frequent recombination is facilitated by the domain structure of bacteriocin proteins. In colicins, the central domain comprises about 50% of the protein and is involved in the recognition of specific cell surface receptors. The N-terminal domain (∼25% of the protein) is responsible for translocation of the protein into the target cell. The remainder of the protein houses the killing domain and the immunity region, which is a short sequence involved in immunity protein binding. Although the pyocins share a similar domain structure, the order of the translocation and receptor recognition domains are switched 〚20〛. As we shall explore further below, the conserved domain configuration of these toxins is responsible for much of the bacteriocin diversity we find in nature.