Background
AMR, WHAT IS IT?
Antimicrobial Resistance (AMR) is when antibiotic medicines are no longer effective amongst organisms, including but not limited to bacteria, fungi, and parasites. [1] Along with the formation of resistance, diseases and infections that used to be treatable now becomes hazardous, and even causes higher chances of disease spread, illness, and more clinical obstacles.
AMR, HOW SERIOUS IS IT?
WHAT IS THE IMPACT?
AMR has caused 1.27 million direct deaths and over 4 and a half million indirect deaths since 2019, and the death toll has since then grown to 21.36 million deaths in 2021. The deterioration of antibiotic drug effects is also putting modern medicine discoveries and other everyday clinical procedures at risk. Clinical services such as but not limited to chemotherapy, surgery, and cesarean sections are some of the most jeopardized protocols in treating patients. The declination of antibiotics as a first-line treatment has also caused a non proportional growth of reliance on second and third line treatment therapies [2]. What is not known to most people is that second and third line therapies often have relatively lower effectiveness, potential for increased toxicity, and higher costs, making poorer countries or lower income families unable to access those resources.
The world is now pressing to research and develop new methods and medicine in backup for the rapidly growing antimicrobial resistance, and it is struggling to keep up with the expedited growth of it. Moreover AMR has created a huge burden on the economy ,it is calculated by The World Bank that AMR can cause up to 3.4 trillion USD lost on gross domestic product (GDP) in just 5 years and 1 trillion USD of additional healthcare cost in 25. Studies have also shown more specifically a financial liability of up to 30 thousand USD per patient affected by AMR[4].
These antimicrobial effects are spreading amongst fields no longer limited to healthcare but community environments, such evolutionary developments are also to be aware of while combating its current effects on the medical infrastructures.
AMR, HOW DOES IT AFFECT THE
ACHIEVEMENTS OF SDG GOALS?
Sustainable Development Goals (SDGs) are the 17 goals the world aims to accomplish before 2030. AMR is caused by not just overuse of antibiotics in medical settings., but for a lot more other various reasons.Antibiotic overuse in animals, often to prevent disease caused by crowded living conditions, has already contributed to the development of antibiotic resistance and poses a high risk of spreading to humans through contact or food. [7]. Wastewater is also a major reason. Research has shown antibiotic levels can be r higher after treatment, and With the society’s tendency to dispose of antibiotic waste into sewage systems, antibiotic resistance continues to frow under these conditions. All of these phenomenons point to destructive effects on maintaining the path of reaching these seventeen goals. Most affected ones include SDG1, no poverty and SDG3, world health and well being. It is estimated AMR could push more than 24 million people into extreme poverty, regarding high medical fees from second and third line treatments from above, and could cause up to 10 million deaths every year, ultimately creating a huge blow on world population and the overall well being of citizens across the nation.
PMR, HOW IS IT CREATED?
Bacteria have long developed defense mechanisms within themselves to combat the effects of harmful antibiotic molecules. There are two main mechanisms bacterias take in doing so, mutational resistance and horizontal gene transfer. [5]
Mutational resistance
In this scenario, usually a subset of bacteria from the original population undergoes mutation, and once the mutation proves its efficacy, the mutation continues as the bacteria reproduces, eliminating the bacteria before mutation. The pathways of mutational functions in this case are usually under one of four categories:
- A decrease in the affinity of the drug
- A decrease in the drug uptake
- Activation of efflux mechanisms to prosecute the harmful molecule
- Global changes in modulation networks
Horizontal Gene transfer
Antimicrobial bacteria used in research and clinical studies are usually derived from natural environments such as the soil. Genetic exchange occurs long before such bacteria are discovered or introduced into laboratory settings. This creates an “environmental resistome”, making it more difficult to combat other bacteria that have developed resistance to commonly used medicines. (e.g. penicillins).
These AMR development usually take place with one of three strategies when undergoing gene transfer:
- Transformation
- Transduction
- Conjugation
In clinical settings such as hospitals which was our initial focus for addressing AMR, resistance spreads most easily. Patients undergoing antibiotic treatment create conditions that favor the transfer of resistance genes, particularly through conjugation, accelerating the spread of antimicrobial resistance.
Our project focuses on the enzymatic degradation of antibiotic’s molecule structure. These enzymes usually attack the drug’s structure by breaking bonds or adding chemical groups. Particularly with penicillin, beta-lactamase is usually the target enzyme that decreases the functions of penicillin antibiotics.
WHAT IS BETA-LACTAMASE?
Beta-Lactamase, is one of the oldest known antibiotic degrading enzymes, they are also the most wide-ranged type. Beta-Lactamase breaks the beta-lactam ring in penicillin, cephalosporins, carbapenems[6], and other related antibiotics. By breaking the beta-lactam rings, antibiotics active structure is then destroyed, making it unable to bind to its targets. This process of hydrolyzing the beta-lactam ring inactivates antibiotics before it can do harm to the bacteria.
There are four main Ambler classes of Beta-Lactamases:
- Class A - the beta lactamase in this class is serine based and plasmid encoded. Being plasmid encoded facilitates spread easily. Many of the beta-lactamases in this class is inhibited by clavulanic acid, sublactam, and tazobactam.
- Class B - Metallo Beta-lactamases. This class of beta-lactamase uses one or two zinc ions to activate a water molecule for hydrolysis. It is not inhibited by traditional beta-lactamase inhibitors but instead inhibited by metal chelators. Metal chelators are molecules that bind to metal ions forming a stable complex called a chelate. New Delhi Metallo-Beta-Lactamase (NDM-1) hydrolyzers almost all beta-lactams, making it one of the most pressing issues in clinical environments.
- Class C - Class C beta lactamases are serine based but structurally different from Class A. This type of beta-lactamase is chromosomally encoded. It is mainly active against cephalosporins.
- Class D (OXA type) - This is also a serine beta-lactamase but structurally different. It is called the OXA type because of its characteristics to hydrolyze oxacillin and cloxacillin efficiently.
REFERENCES
1. World Health Organization. Antimicrobial Resistance. WHO Fact Sheets.
https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance
(accessed 2025/9/27).
2. Ahmed, S. K., Hussein, S., Qurbani, K., Ibrahim, R. H., Fareeq, A., Mahmood, K. A., & Mohamed, M. G.
“Antimicrobial resistance: Impacts, challenges, and future prospects.”
Journal of Medicine, Surgery, and Public Health, 2024, Volume 1.
https://doi.org/10.1016/j.glmedi.2024.100081
3. Svaton, M., Marel, M., Venclicek, O., Kultan, J., Cernovska, M., Hrnciarik, M., Krejci, J., Odrazka, K., & Domecky, P.
“Efficacy of second- and third-line chemotherapy after chemotherapy with platinum doublet and immunotherapy in non-small cell lung cancer: a descriptive study.”
PMC (PubMed Central).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335695/
(accessed 2025/9/29).
4. Poudel, A. N., Zhu, S., Cooper, N., Little, P., Tarrant, C., Hickman, M., & Yao, G.
“The economic burden of antibiotic resistance: A systematic review and meta-analysis.”
PMC (PubMed Central).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10166566/
(accessed 2025/9/29).
5. Munita, J. M., & Arias, C. A.
“Mechanisms of Antibiotic Resistance.”
PMC (PubMed Central).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4888801/
(accessed 2025/9/29).
6. Varela, M. F., Stephen, J., Lekshmi, M., Ojha, M., Wenzel, N., Sanford, L. M., Hernandez, A. J., Parvathi, A., & Kumar, S. H.
“Bacterial Resistance to Antimicrobial Agents.”
Antibiotics (MDPI), 2021, 10 (5), 593.
DOI:
https://doi.org/10.3390/antibiotics10050593
7. Chang, S.-C., Shiu, M.-N., & Chen, T.-J.
“Antibiotic usage in primary care units in Taiwan after the institution of national health insurance.”
Diagnostic Microbiology and Infectious Disease, 2001, 40, 137–143.
DOI:
https://doi.org/10.1016/S0732-8893(01)00256-5
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