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. 2017 Apr 21;1(1):65-74.
doi: 10.1042/ETLS20160016.

The therapeutic potential of bacteriocins as protein antibiotics

Hannah M Behrens  1 , Anne Six  2 , Daniel Walker  2 , Colin Kleanthous  1
Affiliations

The therapeutic potential of bacteriocins as protein antibiotics

Hannah M Behrens et al. Emerg Top Life Sci. .

Abstract

The growing incidence of antibiotic-resistant Gram-negative bacterial infections poses a serious threat to public health. Molecules that have yet to be exploited as antibiotics are potent protein toxins called bacteriocins that are produced by Gram-negative bacteria during competition for ecological niches. This review discusses the state of the art regarding the use for therapeutic purposes of two types of Gram-negative bacteriocins: colicin-like bacteriocins (CLBs) and tailocins. In addition to in vitro data, the potency of eight identified CLBs or tailocins has been demonstrated in diverse animal models of infection with no adverse effects for the host. Although the characteristics of bacteriocins will need further study, results obtained thus far regarding their in vivo potency, immunogenicity and low levels of resistance are encouraging. This leads the way for the development of novel treatments using bacteriocins as protein antibiotics.

Keywords: antibiotics; bacteriocins; colicin; infection; pyocin.

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Conflict of interest statement

The University of Glasgow has filed patents on the use of the protein antibiotics (colicins and pyocins) as therapeutics with DW listed as an inventor. The University of Oxford has filed a patent on methods for the discovery and engineering of bacteriocins with CK listed as an inventor. The authors have no other conflicts of interest.

Figures

Figure 1.
Figure 1.. Import of colicin-like bacteriocins.
Specificity of CLBs is mediated by binding a receptor in the outer membrane of a target cell. An adjacent translocator will then mediate transport into the periplasm. Energy for this transport is provided by either the Tol system for group A CLBs or by the Ton system for group B CLBs. Pore-forming colicin-like bacteriocins then insert into the inner membrane to disrupt the proton motive force (pmf) while nucleases translocate into the cytoplasm. Adapted from ref. [36].
Figure 2.
Figure 2.. R-type tailocins consist of an inner core (C) and sheath, which can be contracted (CS) or extended (ES).
Upon binding a target cell with tail fibres (TFi), attached to the sheath via the base plate (BP), the sheath contracts and inserts the core into the inner membrane of a target cell, consequently depleting the proton motive force. F-type tailocins consist of a flexible rod, made from 23 annuli, to which fibres (Fi) with some globular structures are attached via a distal part (DP). Taken from ref. [46].
See this image and copyright information in PMC

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