*September 3, 1928- It was a dark and stormy night.* Truthfully, it likely was not a “dark and stormy night,” but every great superhero needs a dramatic entrance.
Upon his arrival home from holiday, Alexander Fleming noticed an unusual guest among his Petri dishes of Staphylococcus, a bacterial species known to cause various ailments. In his culture, mold had grown. Further investigation of the cultures would show that immediately around the mold, the Staphylococcus was dead. The mold, identified as Penicillin notatum, was a transformative discovery that would change the face of medicine. Fleming found that his “mold juice” could inhibit and kill various strains of bacteria. Through this discovery, the first true antibiotic was created, Penicillin (1).
Prior to the discovery of Penicillin, infections plagued the world. An injury as small as a cut could become life-threatening if it became infected. Hospitals were overwhelmed with patients and unable to treat them effectively. Although the benefits of various microbes are believed to have been known centuries before penicillin’s discovery, evidenced by the Egyptians’ use of poultices, it was not until Fleming’s discovery in 1928 that a new door opened—the age of antibiotics, our world’s superheroes (1).
Since their introduction, professionals estimate that antibiotics have contributed to a 20+ year increase in human life expectancy (4). Antibiotics save lives daily, combating villainous infections like pneumonia, strep throat, and sepsis; however, as any good superhero story will prove, every hero has their Kryptonite, and antibiotics’ weakness seems nearly undefeatable. *The Thanos of our world- if you will.*
Enter antibiotic resistance…
Since the implementation of antibiotics, selective pressures have resulted in bacteria mutating in ways that favor survival. Although seemingly insignificant, in recent decades, bacteria have rapidly gained resistance, outpacing medicine’s ability to combat it with new antibiotics (2). Certain strains of bacteria, known as “Superbugs,” have garnered resistance to multiple antibiotics, one known bacterium being Methicillin-resistant Staphylococcus aureus (MRSA). Professionals estimate nearly 2 million people are affected by antibiotic-resistant bacteria and that 23,000 die as a direct result each year (2 and 3).
After almost 100 years, it seems strange that antibiotics have decided to gain rapid resistance now. This rapid acquirement of resistance is attributed to overuse and improper use. When used properly, antibiotics work wonders; however, when prescribed and taken excessively, antibiotics destroy our needed healthy bacteria. This allows the resistant bacteria to take over and spread to other people. As doctors continue to overprescribe antibiotics, the problem multiplies. With continued occurrence, we will soon have a problem of intergalactic proportions. *Think Avengers Infinity War.* Surgery will become nearly impossible. Heart problems will become untreatable. Life expectancy will decrease significantly (4).
The first step in addressing antibiotic resistance is for doctors to prescribe antibiotics only when necessary. Still, this does not eliminate the already present problem—many strains of bacteria are becoming resistant to our strongest antibiotics.
*This, my readers, is when our hero finds his sidekick (kind of)…*
Batman and Robin, Captain America and Bucky Barnes, Mermaid Man and Barnacle Boy – every superhero has their sidekick. Against all odds, the sidekick works alongside the hero, bettering them. Together, they’re unstoppable, but apart- well, if you want to know what happens when a superhero and the sidekick are apart, just watch Captain America: The Winter Soldier (although the implications are different).
Adjuvants are compounds that have no microbial activity within themselves. Instead of directly targeting bacteria to kill them, as antibiotics do, adjuvants work alongside antibiotics to combat bacterial resistance, serving as a “power up” (for information on resistance mechanisms, visit: An overview of the antimicrobial resistance mechanisms of bacteria). Since adjuvants do not directly target bacteria to kill them, scientists believe the selective pressures that result in antibiotic resistance should not be present for adjuvants. This effectively means that adjuvants hold the key to effectively ending antibiotic resistance. Furthermore, adjuvants could increase the effectiveness of antibiotics. This would mean that a broader range of antibiotics could be used to treat infections instead of the one or two options today.
Although adjuvants may seem like a distant future, they have already proven promising. For example, clavulanic acid, an FDA-approved adjuvant, is already paired with amoxicillin to treat many common infections. This common pairing is known as Augmentin (5 and 6). Clavulanic acid effectively inactivates the necessary resistance enzyme in bacteria, making it possible for the paired amoxicillin to attack (5).
Although adjuvants prove promising, it is challenging to identify compounds that effectively inhibit enzymes in bacteria. We are screening a comprehensive list of potential adjuvants, including compounds that are FDA-approved for other ailments. With each screen, we hope to find our long-awaited sidekick. This will be confirmed when the inhibition of resistance-contributing enzymes is seen. Once we identify effective adjuvants, we will hold the key to a new timeline. *I personally hope Loki is still alive in this one.*
The fight is not yet over. Our hero continues to fight our villain and his newfound powers, but the help of a trusty sidekick may be just what antibiotics need to finally turn the tide of the war. We must direct our efforts to the antibiotic resistance battle to prevent a lapse in medicine. Efforts include those from the public along with the continued research of scientists. Only take antibiotics when needed. Take antibiotics responsibly, ensuring that you take the entire prescribed amount. This fight needs the help of the whole population. Together, we can work to slow the effects of antibiotic resistance until our sidekick is found.
Antibiotics have come a long way since Alexander Fleming; however, their story is far from over. Continued funding and research will contribute to a happy ending. One could only imagine what a sad one would entail…
Morgan Murphy
Chemistry Major
Class of 2027
References
(1) American Chemical Society International Historic Chemical Landmarks. “Discovery and Development of Penicillin.” American Chemical Society, 2024, www.acs.org/education/whatischemistry/landmarks/flemingpenicillin.html#:~:text=In%201928%2C%20at%20St.%20Mary%27s.
(2) Habboush, Yacob, and Nilmarie Guzman. “Antibiotic Resistance.” PubMed, StatPearls Publishing, Jan. 2024, pubmed.ncbi.nlm.nih.gov/30020649/.
(3) News in Health. “Stop the Spread of Superbugs.” NIH News in Health, Feb. 2014, newsinhealth.nih.gov/2014/02/stop-spread-superbugs.
(4) Staples, Alison. “So What Would Happen If Antibiotics Stopped Working? | ANTRUK.” Antibiotic Research UK, 25 Jan. 2018, www.antibioticresearch.org.uk/happen-antibiotics-stopped-working/#:~:text=It%20has%20been%20estimated%20that.
(5) Uto, Leah R., and Valerie Gerriets. “Clavulanic Acid.” PubMed, StatPearls Publishing, 29 May 2023, www.ncbi.nlm.nih.gov/books/NBK545273/#:~:text=Clavulanic%20acid%20is%20an%20inhibitor.
(6) WebMD. “Drugs & Medications.” Www.webmd.com, www.webmd.com/drugs/2/drug-4333-5050/augmentin-oral/amoxicillin-clavulanic-acid-suspension-oral/details. Accessed 9 July 2024.
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