Bacteriocins are a group of antimicrobial peptides produced by bacteria, capable of controlling clinically relevant and drug-resistant bacteria. They represent a potential drug alternative for replacing current antibiotics to treat diseases caused by resistant bacteria. As we know, the world is facing a significant increase in infections caused by drug-resistant infectious agents. For this reason, bacteriocins are strong candidates to be used as therapeutic agents.
Sterify products exploit the antimicrobial activity of nisin, a polycyclic antibacterial peptide produced by the bacterium Lactococcus lactis that is used as a food preservative. In this article we wanted to share some interesting facts about this new class of antimicrobial agents, exploring and summarizing a recent overview published on frontiers.
- Bacteriocins were first discovered by André Gratia in 1925. He was involved in the process of searching for ways to kill bacteria, which also resulted in the development of antibiotics and the discovery of bacteriophage, all within a span of a few years. He called his first discovery “colicine” because it killed E. coli.
- Bacteriocins display a non-toxic behavior at in vitro assays (Cebrián et al., 2019). This is also confirmed in vivo and clinically. Numerous researches have examined the biosafety and toxicity of bacteriocins utilizing a variety of administration methods, including oral, intraperitoneal, nasal, and topical. In particular, topical application of bacteriocins has been reported to be successfully tested for skin infection with no toxicity effects.
- Bacteriocins can be naturally synthetized by native producers. This mechanism exploits the bacteriocins excretion by dedicated membrane-associated ATP-binding cassette (ABC) transporters or by the general secretion pathway of the cell (Munoz et al., 2011). Bacteriocins can also be naturally synthetized by heterologous producers to increase the bacteriocin production yield from native producers by facilitating the control of gene expression or increasing the production levels. Bacteriocins can be also chemically synthetized.
- As expected, bacteriocins have an outstanding record to kill or reduce pathogens and drug-resistant pathogens during in vitro assessments (Fuchs et al., 2011; Cui et al., 2012; Gabrielsen et al., 2014; Ishibashi et al., 2014; Al Atya et al., 2016; Jiang et al., 2017; Aguilar-Pérez et al., 2018; Ansari et al., 2018; Denkovskienė et al., 2019; Peng et al., 2019; Newstead et al., 2020).
- Although it is a fact that the current literature for bacteriocins produced from Gram-negative bacteria is dominated by bacteriocins toward Gram-positive bacteria (Jamali et al., 2019), there is an acceptable amount of bacteriocins reported to have a strong activity against Gram-negative bacteria, including the pathogenic strains, e.g., the S-type pyocin group from the P. aeruginosa (Ghequire and De Mot, 2014), or the microcin and colicin groups that are vastly reported for E. coli.
- Unlikely to antibiotics, bacteriocins can be engineered to attach anywhere on the cellular outer membrane because they do not have a specific receptor (Bonhi and Imran, 2019) and they can be produced in situ by probiotics (Dobson et al., 2012; O’Shea et al., 2012).
- Bacteriocins are categorized in several ways, including producing strain, common resistance mechanisms, and mechanism of killing. Methods of killing include: pore-forming, nuclease activity, peptidoglycan production inhibition. The naming system is problematic for several reasons. First, it would be more accurate to name bacteriocins according to what they kill if their killing spectrum coincided with genus or species names. However, the bacteriocins frequently possess spectra that exceed the bounds of their named taxa and almost never kill the majority of the taxa for which they are named. Additionally, the bacteriocin’s initial name usually comes from the organism that produces it rather than the specific strain that it kills. Because of this, using this name system as a theoretical foundation is challenging.
- As of 2016, nisin was the only bacteriocin generally recognized as safe by the FDA and was used as a food preservative in several countries. Furthermore, bacteriocins active against E. coli, Salmonella and Pseudomonas aeruginosa have been produced in plants with the aim for them to be used as food additives. Moreover, it has been recently demonstrated that bacteriocins active against plant pathogenic bacteria can be expressed in plants to provide robust resistance against plant disease.
- According to 2019 WHO’s Antibacterial Agent in Preclinical Development Book, 27 of 252 antimicrobial agents in preclinical revision status are considered as antimicrobial peptides. In an independent study, Theuretzbacher et al. (2020) identified the current global antibacterial pipeline and found that 135 of 407 preclinical projects from 314 private and public institutions were related to producing synthetic and natural antimicrobial peptides, natural products, and LpxC inhibitors, and most of these molecules are targeting Gram-negative bacteria.
- The future of this new class of therapeutic agents is intriguing and may lead to novel discoveries. Fields et al. (2020) were the first to design the very first fully de novo bacteriocin by using a machine-learning approach. Acuña et al. (2012) were able to design chimeric bacteriocins that retained the properties to kill both Gram-positive and Gram-negative bacteria. Moreover, other authors have preferred to repurpose the bacteriocins by exploiting their capability against tumor cells (Varas et al., 2020).