INTRODUCTION

Antimicrobial Resistance (AMR) occurs when bacteria, viruses, fungi and parasites no longer respond to antimicrobial medicines (“Antimicrobial resistance”) Antimicrobial resistance was found to have caused an estimate of 23,000 deaths in the United States in 2013 (Tavernise) and an estimated 5 million global deaths in 2019. In recent years, antibiotic resistant bacteria posed significant risk towards the global population and continues to be a challenge scientists must consider during the development of antibiotics. As traditional antibiotics production has fallen over the years, a result of its potential infectivity, the need for innovative and out-of-the box fixes have never been more necessary. However, developing such solutions require navigating through complex topics in both the medical and scientific sphere. This exploration will dive into the complexities and considerations regarding the expansion of innovative antibiotics.

HOW DOES ANTIMICROBIAL RESISTANCE OCCUR?`

Since the discovery of penicillin in 1928, antibiotics have revolutionized medicine. Despite this, there has been a disturbing trend in antibiotic resistance in the past decade. Antibiotic resistance occurs when bacteria evolve to resist the effects of antibiotics. This transpires through various manners. Pathogens develop resistance by neutralizing and altering components of antibiotics; rendering them ineffective. They also alter their own structures and genetic information so that the antibiotic can no longer attach or recognize them through the Horizontal Gene transfer, which includes the processes conjugation, transduction and transformation. Antibiotic resistance also occurs through natural selection, where mutated bacteria resistant to antibiotics reproduce via mitosis; producing clones that retain the same characteristics as their parents.

Pathogens can develop resistance through lesser-known mechanisms such as efflux pumps (“Efflux pump inhibitors for bacterial pathogens: From bench to bedside”), which are protein transport carriers expelling antibiotics, reducing their effectiveness. This forms Biofilm, structured communities of microorganisms that adhere to surfaces, known to evince between a 10 to 1,000 times resistance to antibiotics when contrasted with bacteria of close nature living in planktonic states (“The Role of Bacterial Biofilms in Antimicrobial Resistance | ASM.org”).

Staphylococcus Aureus is a gram-positive bacteria that causes skin infections, pneumonia and endocarditis (“Staphylococcus aureus Basics | Staphylococcus aureus”). Current studies have shown that 30-50% of Staphylococcus aureus are Methicillin-resistant and 40-60% of Staphylococcus aureus strains show resistance to at least one antibiotic. (“Antimicrobial Susceptibility of Staphylococcus aureus Isolated from Recreational Waters and Beach Sand in Eastern Cape Province of South Africa”). This bacteria develops resistance to certain antibiotics by producing an enzyme known as beta-lactamase, which hydrolyzes the beta-lactam rings of antibiotics such as penicillin (Lowy).

HOW DO SCIENTISTS TACKLE AMR DURING THE PRODUCTION OF ANTIBIOTICS?

Vaccines have been a cornerstone for public health, providing immunity against infectious diseases. They have been responsible for preventing multiple pandemics from having disastrous effects. They have also helped in the eradication of diseases such as Smallpox and rinderpest. Despite this, the threat of Antimicrobial Resistance has led to even longer formulation periods for vaccines, with vaccine research scientists having the responsibility of not only formulating the vaccines, but also taking into consideration the risk of AMR. The 2014-2016 outbreak of Multi-drug resistant Tuberculosis serves as a relevant example on displaying the meticulousness of vaccine formulations.

Antigen selection becomes a very important factor when formulating a vaccine against TB. Mycobacterium tuberculosis, the causative bacterium, has developed various elaborate immune evasion mechanisms; hence, finding the effective components of the vaccine becomes absolutely essential. Various proteins like ESAT-6 and CFP-10 have been tried and show promising results in inducing strong immune responses (“Importance of adjuvant selection in tuberculosis vaccine development: Exploring basic mechanisms and clinical implications”).

TB vaccines, such as Bacille Calmette-Guérin, have been in use for many decades; however, the efficacy against MDR-TB is limited. Other new approaches are viral vector platforms or mRNA technology (“A century of BCG vaccination: Immune mechanisms, animal models, non-traditional routes and implications for COVID-19”).

A CHOSEN REAL-WORLD EXAMPLE OF A VACCINE TARGETING AMR

What if a simple vaccine could prevent a debilitating infection that often arises from antibiotics use? A real-world example of a Vaccine targeting AMR would be the formulation of the Clostridium difficile Vaccine.

Clostridium difficile is a gram-positive bacterium that is responsible for causing debilitating gastrointestinal infections, especially following the use of antibiotics. Side effects of infections include severe diarrhea and life threatening complications. The emergence of antibiotic resistant strains of this bacterium cause further threat to the lives of those suffering from Clostridium difficile. The primary target for the C. Difficile vaccines are Toxin A and Toxin B, both of which play crucial roles in its pathogenicity. These toxins are responsible for disrupting the intestinal function as well as contributing to the inflammation. During the vaccine development process, Researchers use recombinant proteins to mimic the structure of the toxins. For example, the Cdiffense vaccine (developed by Medicago), is composed of both Toxin A and B in order to elicit an immune response without causing the disease. Additionally, Adjuvants may also be used in the vaccine formulation as a means to enhance the immune response, to provide for long lasting and robust immunity. Multiple phases of clinical trials are also carried out. Firstly, tests are carried out on animals to assess its safety and efficacy. Phase I primarily focuses on safety and immunogenicity of volunteers, whereas phase II evaluates the efficacy of the vaccine in a larger batch of volunteers by analyzing the immune response.

The formulation of the C. difficile vaccine was a model example of a vaccine formulated to combat AMR. This is because C. difficile infections often occur after the use of antibiotics, disrupting the gut flora and allowing the bacterium to proliferate.