The therapeutic potential of bacteriocins as protein antibiotics

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.

Conditionally Redundant Bacteriocin Targeting byPseudomonas syringae

“…Empirical and genomic data has shown that bacteria often encode multiple antagonistic traits, particularly among Pseudomonas strains 10,18–20 . In contrast to broad spectrum antibiotics, which have been widely used for nearly a century to combat and control bacterial pathogens under clinical and agricultural settings, bacteriocins have remained underutilized as pathogen control agents, despite documented potential 21–25 . This is partially because bacteriocins are thought to have a narrower spectrum of activity than more widely used antibiotics, which in the past has been considered detrimental but now is sought given worries about off-target effects on the microbiome.…”

Infection therapy: the problem of drug resistance – and possible solutions

“…Thuricin produced by Bacillus thuringiensis kills a wide range of Clostridium difficile isolates in a colon model (Rea et al, 2010) without significant impact on the human gut microbiota (Rea et al, 2011). Bacteriocins are also produced by E. coli (colicins) or Pseudomonas (pyocins), and prevent E. coli diarrhoea in pigs and Pseudomonas aeruginosa infection in wax moths respectively (Behrens et al, 2017). Microcins produced by the probiotic E. coli Nissle strain limited the expansion of competing Enterobacteriaceae in mice suffering from intestinal inflammation and might thus represent a possible treatment mode for enterobacterial colitis (Sassone-Corsi et al, 2016).…”

Pyocin efficacy in a murine model ofPseudomonas aeruginosasepsis

“…A potential alternative therapeutic strategy to treat multidrug-resistant is the use of the highly potent and narrow spectrum bacteriocins as protein antibiotics 12 . Bacteria produce these very diverse and widespread proteins during intraspecies competition, where they kill only bacteria closely related to the producing strain 13,14 . Bacteriocins from P. aeruginosa can be classified into different categories, with the most abundant S-type pyocins closely resembling colicins from Escherichia coli 14,15 .…”