Lantibiotics: A Novel Antimicrobial Agent

By Stanley Yu

Take a look at the PURELL Hand Sanitizer sitting on the corner of your desk. What does that 99.99% killing germ indicator mean? Why not 100%? Well, various germs and bacteria strains are resistant to the antimicrobial properties of sanitizing agents such as hand sanitizer. Most notably, K. pneumoniae and P. aeruginosa are both bacterial strains that have developed resistance over the years (Muleba). As a result, many individuals in the medical field have sought other agents that may combat microbes in an attempt to inhibit the development of pathogenic infections. Lantibiotics, first discovered in the 20th century, hold promise in the potential development of pharmacological agents to suppress bacterial and microbial infections (van Staden). There are various advantages and drawbacks of lantibiotics and antibiotics, and this analysis aims to highlight bacterial and antibacterial agent interactions, including the effectiveness of lantibiotics and the process of antibiotic resistance.

Antibiotic resistance, although now well-established in modern society, had not always been well understood. In the 1920s, the influenza virus, then a pandemic, afflicted various individuals across the globe. Alexander Fleming, a bacteriologist working in London, was studying this virus and accidentally exposed his culture of staphylococci to contamination (Lobanovska). This bacterial colony was contaminated by Penicillium notatum, a fungal contaminant that produced penicillin, which we now understand as the first antibiotic. What Fleming then observed was that when contaminated, the bacterial colony’s growth was inhibited, a revolutionary discovery in the medical field. In the advent of the 21st century, scientists have developed and researched the complex interactions that penicillin has on bacterial cells, specifically their cell walls. In most bacteria, their cell wall is made up of peptidoglycan (PGN), a crucial component in the protection and stability of the cell wall. However, when penicillin is administered to bacteria, it irreversibly binds to the enzyme responsible for connecting peptide bridges in PGN, transpeptidases. This inhibits the formation of peptide bridges and as a result, the production of PGN, exposing bacteria cells to potential lysis. Another benefit of this method is that penicillin specifically targets prokaryotic cells like bacteria, as eukaryotic cells and somatic cells in the human body don’t include PGN, nor have a cell wall. This advancement throughout history has had several benefits in combatting virulent infections like pneumonia, influenza, and strep throat. However, the exploitation of this revolutionary process in the 20th century would have unintended consequences, that still adversely affect medical advances to this day.

A property common in many bacterial species is the ability to transfer genetic information in between different cells. This adaptation, known as horizontal gene transformation, has changed how effectively bacteria can respond to environmental pressures, such as antibiotics. When antibiotic resistance first develops in a bacteria cell through random genetic mutations, only that bacterial cell possesses antibiotic resistance genes (ARGs). However, through horizontal gene transfer, ARGs, which are typically located on a bacterial plasmid - a circular piece of prokaryotic DNA - can be transferred to other bacterial cells to disseminate the trait throughout the population. Many host bacteria cells that possess ARGs frequently utilize conjugation to transfer their genetic material. Conjugation, compared to other modes of transmission like transformation and transduction, involves the transfer of specifically plasmids, through the pilus, a pore formed between adjacent bacteria cells (Tao). This form of cell communication permits the quick dissemination of antibiotic resistance among a population. As a result, the continuous uncontrolled usage of antibiotics can hinder the effectiveness of many medical practices due to the rapid antibiotic resistance that bacteria undergo. This resistance has had major implications involving the usage of antibiotics in the medical field and the proper dosages of antibiotics to cure pathogenic infections. As a result, many scientists started to investigate other forms of antibiotic resistance, most notably, agents that could substitute and imitate the effects of antibiotics. This has steered scientists to investigate the potential of lantibiotics, otherwise known as lanthipeptides that have antibacterial properties. 

Historically, how did lantibiotics arise as food preservatives? Lantibiotics, a form of peptide antibiotics, prevent bacterial growth by primarily targeting lipid II, a precursor to the bacterial cell wall. The resulting complex that is formed thus inhibits bacterial cell wall synthesis, preventing the growth of bacteria. Consequently, many supermarkets and food production facilities utilize lantibiotics, the most popular being nisin, to increase shelf life by targeting gram-positive bacteria. Gram-positive bacteria are particularly vulnerable to lantibiotics as they have several more layers of peptidoglycan than gram-negative bacteria have, allowing lantibiotics to suppress gram-positive bacteria more effectively than gram-negative bacteria. Another advantage that lantibiotics provide in the food sector is the low levels of reported resistance compared to traditional antibiotics (Draper). This observation has inspired scientists to utilize lantibiotics in the medical field by investigating its antimicrobial properties.

Many scientists, including university scientists, have begun investigations regarding how lantibiotics can affect the human microbiome. Specifically, scientists from the University of Chicago have studied how nisin-like lantibiotics can adversely affect the human gut microbiome. By studying public databases of gut bacteria genomes, Postdoc Zhenrun Zhang and his team discovered that these nisin homologs targeted both commensal bacteria and pathogens (Zhang). Through this, we understand that lantibiotics target bacterial cells indiscriminately, which has major implications on how efficiently and fast we can apply lantibiotics in the medical field. Despite this drawback, Zhang and his team simultaneously conducted research on how lantibiotics could be harnessed effectively. In a study on 4 distinct microbes, Zhang and his team discovered that the lantibiotics that the microbes produced protected mice against antibiotic-resistant Enterococcus infections (Zhang). This discovery demonstrates how bacteriocins like lantibiotics can be utilized in effective ways while minimizing potential drawbacks. Ultimately, although lantibiotics are heavily underresearched, their antimicrobial properties have potential in medical applications for mitigating pathogenic infections.

In a world where pathogenic infections run rampant, lantibiotics, a form of bacteriocin and lanthipeptide, possess the potential to suppress microbial activity, representing a replacement for traditional antibiotics, whose antimicrobial properties are diminished due to horizontal gene transformation in bacteria populations. When applying lantibiotics to the medical field, it is important to harness the advantages of lantibiotics while remaining attentive to potential adverse effects on the human microbiome. 

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