Bacteriocins — a viable alternative to antibiotics?

Subjects

Key Points

  • Solutions are urgently required for the growing number of infections caused by antibiotic-resistant bacteria and to address the fact that broad-spectrum antibiotics can considerably harm the commensal human microbiota.

  • Bacteriocins are potential alternatives to traditional antibiotics. These peptides, which are produced by many bacteria, can have a high potency and a low toxicity, can be produced in situ by probiotics and can be bioengineered. Both broad- and narrow-spectrum bacteriocins exist.

  • Bacteriocins function through different mechanisms that are frequently distinct from those used by antibiotics. Bacteriocins can be broadly classified into those that target the cell membrane and those that function within the cell, targeting DNA, RNA and protein metabolism.

  • Resistance to bacteriocins is a potential problem. In some cases, resistance arises at a sufficiently low rate to allow commercialization of the peptide in its natural form. In other cases, knowledge of the potential resistance mechanisms could be crucial for minimizing the emergence of resistance when clinical applications commence.

  • Many bacteriocins possess properties which suggest that these peptides could be of value in clinical settings. However, to date, the primary focus for their use has been on animal, rather than human, health.

  • A lack of sufficient investment has been a significant problem with respect to the medical application of bacteriocins. Notably, however, there is evidence to suggest that issue is finally being addressed.

Abstract

Solutions are urgently required for the growing number of infections caused by antibiotic-resistant bacteria. Bacteriocins, which are antimicrobial peptides produced by certain bacteria, might warrant serious consideration as alternatives to traditional antibiotics. These molecules exhibit significant potency against other bacteria (including antibiotic-resistant strains), are stable and can have narrow or broad activity spectra. Bacteriocins can even be produced in situ in the gut by probiotic bacteria to combat intestinal infections. Although the application of specific bacteriocins might be curtailed by the development of resistance, an understanding of the mechanisms by which such resistance could emerge will enable researchers to develop strategies to minimize this potential problem.

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Figure 1: Narrow-spectrum activity of thuricin CD.
Figure 2: Probiotic delivery of bacteriocins.
Figure 3: Mechanism of action of representative bacteriocins.

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Acknowledgements

Related work in the authors' laboratories is supported by the Irish Government under the National Development Plan; by the Irish Research Council for Science Engineering; by Enterprise Ireland; and by the Science Foundation Ireland (SFI) through the Alimentary Pharmabiotic Centre, University College Cork, Ireland (which is supported by the SFI-funded Centre for Science, Engineering and Technology) and through two Principal Investigator grants, to P.D.C. and to C.H. and R.P.R.

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Correspondence to Paul D. Cotter or R. Paul Ross or Colin Hill.

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Protein Data Bank

Glossary

Probiotics

Live microorganisms that confer a health benefit on the host when administered in adequate amounts.

Median effective dose

The amount of an antimicrobial that is required to produce a specific effect in half an animal population.

Pathobionts

Microbial components of the gastrointestinal tract that have the potential to cause disease.

Isogenic

Pertaining to a microbial strain derivative: identical to the parental strain except for a defined mutation.

Siderophore

A low-molecular-mass compound that binds ferric iron extracellularly to form a stable chelate for transport of iron into the cell.

Porin

A large protein that crosses a cellular membrane and acts as a pore through which molecules can diffuse.

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Cotter, P., Ross, R. & Hill, C. Bacteriocins — a viable alternative to antibiotics?. Nat Rev Microbiol 11, 95–105 (2013). https://doi.org/10.1038/nrmicro2937

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