Potential applications of bacteriocins as bioactive substances for human health

Abstract

Lactic acid bacteria are constituents of most of the indigenous microbiota or mucosarelated ecosystems, both in humans or animals. During the last years, many bacteriocins produced by bacteria classified into this group were described. Bacteriocins are ribosomally-synthesized antimicrobial peptides produced by a wide range of bacteria. Historically, they were used as bioactive compounds to prevent the growth of pathogen or spoilage microorganisms in foods. The most widely used is nisin, produced by Lactococcus lactis, that is included in the CODEX and has the GRAS (Generally Recognized as Safe) status to be incorporated into different types of processed or longterm storage foods. As bacteriocins are active against many pathogens, potentially pathogens or some drug-resistant pathogens, some of them have been thought as alternative bioactive substances to avoid the broad side-effects and alarming resistance dissemination produced by the use of classical antibiotics. Our research group is working in the design of a beneficial product to prevent prevent women urogenital infections, and we were the first to describe salivaricin CRL 1328, a bacteriocin produced by Lactobacillus salivarius isolated from human vagina. This bioactive compound is heat-stable, and active against a wide variety of urogenital pathogens. The molecular characterization of salivaricin indicates that is constituted by two structural peptides and the evaluation of the mechanism of action reveals that acts by dissipating the proton motive force of the sensitive pathogens. As we are interested to incorporate salivaricin into a pharmaceutical product, the optimization of the culture media and physico-chemical conditions for the higher production were determined. And also the stability to the freeze-drying process and to the long term storage conditions was studied. Some of these experiments were performed by the application of statistical methods that allowed a faster and easier interpretation of the experimental results obtained. The incorporation of bacteriocins as bioactive compounds in a pharmaceutical product needs different type of studies to demonstrate the no existence of adverse effects, which must be performed both in in vitro and in in vivo experimental systems. Most of the bacteriocins do not exert significant cytoxicity or hemolytic activity against human erythrocytes in in vitro assays. Experiments in animal models have shown the success of some lantibiotics for the treatment of infections produced by Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA), and also in the prevention of gingivitis. Nisin is included into a pharmaceutical product to prevent cow mastitis, and is proposed as spermicidal for human use. In this chapter, a revision of many of the bacteriocins described for prevention of human health are reviewed, together with those available commercially, evaluated by in vitro or in vivo assays. Up today, the use of bacteriocins as bioactive compounds into pharmaceutical products for human use has not been accepted yet by the regulators or reference organizations. There are a wide variety of bacteriocins produced by different bacterial genera that must be further studied. More complex experiments are needed to encourage and support the inclusion of these types of bioactive substances into products that could be applied to prevent or treat many of the wide arrays of pathogenic microorganisms that affect human and animal health.