Bacteriocins - Antibacterial by Bacteria

By Eugene Lim

Humanity has come a long way. From mere monkeys roaming Eastern Africa, to dominating the global ecosystem, it’s an undeniable fact that humanity is much more advanced than it was 5-6 million years ago. One area where the human potential for progress is evident is in the field of medicine. It was only two and a half millennia ago that humanity first started to think about illness and the body in a scientific manner throughwith Hippocrates’s theory of the four humors. Only half a millennium ago, Andreas Vesalias revolutionized the study of Anatomy and Physiology, and only 2 centuries ago Edward Jenner created the first vaccine and Louis Pasteur popularized the germ theory of disease. Arguably one of the most important advances in medicine, however, was the discovery of the first antibiotic, penicillin, in 1928 by Alexander Fleming. Bacteria have long been one of humanity’s greatest adversaries. In the age before antibiotics and modern medical sterility, a single cut could kill a person. However, the introduction of antibiotics brought those days to an end. Unfortunately, the popularization of these wonder drugs could bring these days back. The misuse and overconsumption of antibiotics has caused the emergence of newer and stronger bacteria, coined superbugs. (Joo & Choi 2020) These so-called “superbugs” are now resistant to nearly every antibiotic in the human arsenal. In the United States alone, nearly 2.8 million people are infected with these superbugs and almost 35,000 people die from antimicrobial resistant bacteria a year. (Center for Disease Control, 2024) However, a new weapon may assist in humanity’s fight against these new foes. A substance called bacteriocins produced by bacteria may be humanity’s ultimate ally in their plight against bacteria.

Bacteriocin is an all encompassing term that refers to a wide range of potent antimicrobial amino acids, produced by bacteria. Bacteriocins were discovered nearly a century ago by Belgian microbiologist André Gratia. These toxic peptides can range from highly complex structures encoded by multiple bacterial genes or simple linear chains of amino acids. Bacteriocins can generally be classified by the cell wall types of the bacteria that produce them, being classified as either gram negative or gram positive. Bacteriocins are then further subdivided into various groups by their size (and thus complexity) (Zimina et al. 2020). Since their discovery in 1925 however, bacteriocins have only been widely adopted in the food preservation industry, but with the global rise of antimicrobial resistance in bacteria, bacteriocin research has recently picked up steam in the field of microbiology. This is mainly due to the various advantages that bacteriocins present over traditional antibiotics. This renewed interest in academia has now revealed the great promise that bacteriocins hold. Bacteriocins are now being researched for use in the modulation of food microbiomes, antimicrobial food packaging, bio-sanitizers and antibiofilm, pre/postharvest biocontrol, functional food, growth promotion, and sustainable aquaculture(Reuben & Torres 2024). These widespread potential applications in addition to the role bacteriocins play in the fight against antibiotic resistance underscores the importance of this reemerging therapy in our modern world. 

As mentioned previously, bacteriocin therapy holds a variety of advantages over traditional antibiotics. One of which lies in the ability of bacteriocins to differentiate between friend and foe. Amongst the main disadvantages of traditional antibiotics lies in their very nature, antibiotics by definition (anti, meaning against or opposed and biotic, relating to life) destroy all types of bacteria. This inability to differentiate the beneficial bacteria, which compose the body’s internal microbiome, and pathogenic bacteria, can impede bodily function and destroy the internal balance of the body (homeostasis), which causes many of the side effects associated with traditional antibiotics. (Patangia et al. 2022) However, bacteriocins present a more specific and targeted approach to combating bacterial infections; they target and kill only specific strains of bacteria while ignoring others. (Reuben & Torres 2024) This lets bacteriocin therapy not only be just as, if not more, effective as antibiotics but also without the unwanted side effects of a decimated internal microbiome. 

Another advantage that bacteriocin therapy offers is their effectiveness against antibiotic resistant bacteria. Many cases of bacteriocins inhibitory effects against antibiotic resistant bacterial infections have now been reported. Methicillin-resistant Staphylococcus aureus (MRSA) (Piper et al. 2009), vancomycin-resistant Enterococcus (Oman and van der Donk 2009) and Clostridium difficile (C.Diff) (Le Lay et al. 2016) have all been shown to have been substantially affected by bacteriocin therapy in one way or another. Additionally bacteriocin therapy has been shown to be highly effective against certain gram negative bacteria which are generally less responsive to traditional antibiotic treatments. Some of these include Moraxella catarrhalis, Neisseria spp. and Haemophilus influenzae (Castiglione et al. 2008). All of these cases underscore the importance of bacteriocins in the ongoing fight against antibiotic resistance both in academia and in the field. 

Bacteriocin therapy not only offers an alternative to antibiotics but a potential companion. Many aspects of bacteriocins enable them to reach a higher level of effectiveness when paired with antibiotic treatments. One of these is the fact that many bacteriocins kill bacteria in a different way from most traditional antibiotics. Whilst antibiotics mainly “kill” bacteria by preventing their reproduction, mainly targeting DNA essential to bacterial reproduction, most bacteriocins simply work by killing individual bacteria, forming pores in their cell walls and essentially draining the life out of their target. This difference in mode of action between traditional antibiotics and bacteriocins means that the risk of cross resistance developing is significantly lower but antimicrobial potency is significantly higher. (Soltani et al. 2020) Additionally the fact that the bacteria in question must adapt to multiple pressures as opposed to just one may also help eradicate a greater percentage of the total bacterial infection reducing risk of a reemergence of a stronger resistant strain. 

In an age where modern medicine has protected the lives of millions, nay billions from the horrors of bacterial dominance, the imagination of humanity simply can't imagine a simple paper cut giving someone life threatening sepsis, or a rusty nail giving them fatal tetanus. However, the rise of antibacterial resistance may plunge humanity back into those dark times. The emergence of new techniques to combat the reemergence of our most primal enemy is paramount in this time. It is for this reason that it is extremely important to know about alternative therapies such as bacteriocin therapy. The emergence of alternatives to antibiotics can help to sustain this antibacterial bliss that humanity has enjoyed since Fleming’s discovery of penicillin in 1928. 

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