Combating Antimicrobial Resistance

By Alexia Bove


Artwork by Alexia Bove

Since their discovery, antibiotics have been regarded as one of the most significant advancements in medicine. The commercial production and use of these wonder drugs has shaped modern medicine - infection is no longer the leading cause of death in the United States, invasive procedures have lower mortality rates, and life expectancy has skyrocketed (Adedeji, 2016). Antibiotics seem too good to be true...and it turns out they are.


As antibiotics were used recklessly for decades, from growth promotion in livestock to inappropriate prescriptions, something dangerous was brewing. Exposing bacteria to such high levels of antibiotics killed some of them, but for others it provided selective pressure to evolve mechanisms to evade the drugs, creating a population of bacteria resistant to antibiotics. As our front line drugs become increasingly ineffective, patients around the world are facing lengthier hospital stays and more expensive bills as doctors struggle to cure their infections. Today, the World Health Organization names antibiotic resistance one of the current biggest threats to global public health (World Health Organization, 2018).


Long story short: it’s time to get creative.


Researchers with Genentech Inc. have done just that, developing a potential treatment for one of the most infamous antibiotic resistant superbugs, methicillin-resistant Staphylococcus aureus, better known as MRSA. The leading bacterial pathogen in the world, S. aureus has recently evolved a new strategy to evade antibiotics - hiding inside our cells. And this scary hide and seek isn’t the only mechanism bacteria have evolved to resist antibiotics - some have pumps to remove the drug from the cell, some modify receptors so the drug can’t bind, and some can even physically alter the drug, making it ineffective. Some form of resistance has been seen in almost twenty major human pathogens, with about 2.8 million antibiotic resistant infections per year in the United States alone (CDC, 2019).


To combat this, Sophie Lehar and her team have created a new delivery system to bring antibiotics into the cell along with S. aureus, and potentially other intracellular bacteria. The team attached an antibiotic to an antibody, creating a duo that can enter the immune cell along with the pathogen. Antibodies are proteins produced by immune cells that specifically bind to one type of pathogen, flagging it to be consumed by other immune cells in a process called phagocytosis. During phagocytosis, both the pathogen and the antibody bound to it enter the immune cell, so when an antibiotic is attached to the antibody, it is able to kill the bacteria within the cell, where a normal antibiotic would not have access.The study found that a single dose of the antibody-antibiotic treatment was more effective than a twice daily dose of vancomycin, the standard treatment for MRSA, over a four day period (Lehar et al., 2015).


While this strategy still involves the use of antibiotics, meaning there will always be potential for resistance, it marks a step in the right direction when it comes to developing new treatments against bacteria. For the first time in decades, it is no longer enough to just throw an antibiotic at an infection. Coming up with solutions like these will only become more critical over time as resistance to even last resort antibiotics has been observed with increasing frequency. If we can’t evolve our medicines to reflect the evolution of pathogens, these micro bugs are going to turn into a macro problem.


References:


Adedeji W. A. (2016). THE TREASURE CALLED ANTIBIOTICS. Annals of Ibadan

postgraduate medicine, 14(2), 56–57.


Centers for Disease Control and Prevention (CDC). (2019, November 4). About Antibiotic

Resistance. Retrieved from https://www.cdc.gov/drugresistance/about.html


Lehar, S., Pillow, T., Xu, M. et al. Novel antibody–antibiotic conjugate eliminates intracellular

S. aureus. Nature 527, 323–328 (2015). https://doi.org/10.1038/nature16057

World Health Organization. (2018, February 5). Antibiotic resistance. Retrieved from

https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance



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