A Novel Way to Treat Multidrug-Resistant Diseases
By Eunice Tsang
We see labels like “antibacterial,” “antimicrobial,” and “antibiotics” so often in soaps, detergents, and medications. These antiseptics protect us from harmful viruses, bacteria, and other pathogens. However, microorganisms have the ability to change their genetic make-up and pass down their genes to the next generation, allowing them to thrive in the presence of antiseptics. The microorganisms that have the capability to survive in the presence of antibiotics have a better survival rate than the ones that do not. They are known to cause a type of disease known as multi-drug-resistant disease. These diseases cannot be treated with conventional antibiotics. As a result, they have been a major health concern recently.
According to the CDC, more than 2.8 million antibiotic-resistant infections occur in the US every year. Drug-resistant pathogens—also known as superbugs—can obtain new resistance mechanisms in many different ways. For instance, they can get genes from their neighbors, change their own genetic makeup, or pick up genetic information from dead organisms. One common pathogen is the Mycobacterium tuberculosis, a bacteria that causes tuberculosis. This bacteria is considered multi-drug resistant because patients who suffer from tuberculosis often have to be treated with a regimen of several drugs for more than half a year (“U.S. National”). Multi-drug resistant bacteria called Methicillin-resistant Staphylococcus aureus (MRSA) can even spread from patient to patient in hospitals, leading to serious public health concerns. Though scientists and researchers have developed new antibiotics to fight against drug-resistant pathogens, these drugs often generate very low profit because they cannot compete with other easily accessible antibiotics on the market. For example, Amoxicillin, a common antibiotic that can treat a broad range of diseases, can be mass-produced at a very low cost. In contrast, the estimated cost of developing an antibiotic is around $1.5 billion (Towse et al., 2017).
To solve this problem, scientists are exploring the possibility of using natural agents to fight off these superbugs. Research studies have shown that antimicrobial peptides (AMPs) can be a promising alternative to antibiotics for treating human infections. These peptides can be extracted from microorganisms such as bacteria and fungi (Huan et al., 2020). They have a broad spectrum of antibiotic activities against a variety of antibiotic-resistant organisms. For example, they can starve the cells by eliminating the nutrients that are essential for their growth, interfere with gene signaling pathways, and induce apoptosis (programed cell death). Unlike other expensive synthetic antibiotics on the market, they can be acquired naturally from organisms and are less prone to bacterial resistance.
One particular research study has shown that AMPs are effective against a parasitic sandfly called Leishmania. Leishmania causes a disease known as Leishmaniasis. Some common symptoms include fever, skin lesions, and skin sores that heal very slowly. Unfortunately, there is a very limited treatment option because current drugs in the market have a high toxicity. It is difficult to find a drug that can kill the bacteria efficiently while making sure that our own cells remain unaffected. Antimicrobial peptides called KDEL (synthetic 4-amino acid peptide lysine, aspartic acid, glutamic acid, and leucine) have been shown to be effective in treating this disease. KDEL works by disrupting the cell membrane structure of the parasite (Cao et. al., 2019). Microscopic observation shows that the pathogen swells and bursts open in the presence of KDEL. Most importantly, this study shows that KDEL has no cytotoxicity, which means there is no evidence to show that it is harmful to our own cells.
Although this research study is only applicable to Leishmania, AMPs can be applied to a broad range of diseases. A few AMPs are already in their late clinical development stage, so perhaps they will be available in the market in the near future (Huang et al., 2020). AMPs can potentially replace conventional antibiotics and become the next “superhero.” Hopefully, patients who are currently suffering from multi-drug resistant diseases can get the necessary treatment they need in the future.
Cao, L., Jiang, W., Cao, S., Zhao, P., Liu, J., Dong, H., Guo, Y., Liu, Q., & Gong, P. (2019). In vitro leishmanicidal activity of antimicrobial peptide kdel against Leishmania tarentolae. Acta Biochimica Et Biophysica Sinica, 51(12), 1286–1292. https://doi.org/10.1093/abbs/gmz128
Huan, Y., Kong, Q., Mou, H., & Yi, H. (2020). Antimicrobial peptides: Classification, design, application and research progress in multiple fields. Frontiers. https://www.frontiersin.org/articles/10.3389/fmicb.2020.582779/full.
Towse, A., Hoyle, C. K., Goodall, J., Hirsch, M., Mestre-Ferrandiz, J., & Rex, J. H. (2017). Time for a change in how new antibiotics are reimbursed: Development of an insurance framework for funding new antibiotics based on a policy of risk mitigation. Health Policy, 121(10), 1025–1030. https://doi.org/10.1016/j.healthpol.2017.07.011
U.S. National Library of Medicine. (n.d.). Leading antimicrobial drug-resistant diseases | NIH MedlinePlus Magazine. MedlinePlus. https://magazine.medlineplus.gov/article/leading-antimicrobial-drug-resistant-diseasesW