So far, I have largely concentrated on pathogens that no longer seriously affect us in this modern world. But, of course, there is a price we pay for such luxuries. One of which would be the risk of healthcare-associated pathogens and the accompanying antibacterial resistance, as seen in the evolutionary story of Staphylococcus aureus. S. aureus is a ubiquitous, Gram-positive, bacterium that approximately 30% of the human population carry within their noses and can even be a member of our skin’s microflora. This classifies S. aureus as an opportunistic pathogen, as it generally will not cause illness except in certain cases/under certain conditions, especially within those experiencing weakened immune systems or pre-existing conditions, hence the reason the pathogen generally thrives within hospital and healthcare settings, However, widespread community infections are recently emerging, within the US and worldwide, among healthy individuals.
Although S. aureus is naturally susceptible to almost every antibiotic, ongoing antibiotic resistance is a great cause for concern as the organism can readily gain resistance to multiple antibiotics, therefore limiting treatment options. In fact, it was S. aureus’ exceptional susceptibility that eventually led to the discovery of the first antibiotic, Penicillin, as found by Alexander Fleming. In 1928, the scientist continued his experiment in which he was working with staphylococcal colonies within petri dishes. One of the plates was left opened near a window which began to grow mold. Fleming noted areas of bacterial clearing within proximity to the mold colonies. After isolation and identification of the mold, he learned that all Gram-positive bacteria were susceptible to this “mould juice” produced by the mold colonies. He named his finding “Penicillin”, which marks the beginning of “The Antibiotic Era” (despite penicillin application not occurring until 1940 to treat WWII soldiers, as there was little enthusiasm within the scientific community upon his discovery, initially). Although it was hardly the mid-1940s before penicillin resistant cases of S. aureus were noted within healthcare settings, only a few years into the antibiotic’s introduction into the clinical practice. Within 10 years, resistance was viewed as a significant problem communities were facing.
“I did not invent penicillin. Nature did that. I only discovered it by accident.”
After the introduction of the antibiotic, methicillin, around 1960, resistance to this antimicrobial was almost immediately noted in a published article in 1961 describing the drug resistant strain. In response to earlier penicillin resistance, vancomycin was discovered in the 1950s, but was reserved for patients with serious b-lactam allergies due to perceived toxicity of the newer drug at the time.
Today, there are several different levels of antibiotic resistant S. aureus including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Staphylococcus aureus (VRSA). Although most have heard “MRSA” all S. aureus are capable of producing infection, MRSA is just often better known. This constantly evolving antibiotic resistance is often possible due to horizontal gene transfer from outside. However, chromosomal mutation and antibiotic selection can also serve as a route of resistance acquisition for bacteria.
Penicillin works against microorganisms in disrupting cell wall synthesis during replication whereas methicillin is a partly synthetic derivative of penicillin, in which a structural modification was added to original penicillin. This modification added protection from the recently evolved bacterial strains containing penicillinase/beta-lactamase, making it resistant to the bacteria’s efforts at breaking down the antibiotic’s essential beta-lactam ring, central to this drug’s antimicrobial activity.
Vancomycin is currently considered the last line of defense against S. aureus, which has also led to the emergence of vancomycin-resistant S. aureus. Vancomycin acts against susceptible bacteria in inhibiting the second stage of cell wall synthesis.
Research continues in understanding the forces that direct evolution of drug-resistant organisms, as they may generally begin within the containment of hospitals, but, through detailed modifications, can arise within our communities as virulent pathogens to harm even the healthiest humans. What we can have an effect on now is to eliminate the overuse (and misuse) of antibiotics, as this is obviously a contributing factor to the rapidly evolving antimicrobial-resistant strains of bacteria.
Furthermore, the innovation of new, rapid diagnostic technologies aid in the proper treatment of infections and are, hopefully, making their way to be widely utilized throughout clinics. Alternatives to antibiotics are also gaining attention of researchers in the treatment of bacterial infections. Although this already exists (in its simplest form) in the prevention of infection by proper hygiene practices and cleanliness.
“When I woke up just after dawn on September 28, 1928, I certainly didn’t plan to revolutionize all medicine by discovering the world’s first antibiotic, or bacteria killer. But I suppose that was exactly what I did.”
-Alexander Fleming
In 1936, Fleming accurately predicated our future by telling colleague and friend, Dr. Bill Frankland, “there will be a revolution, but doctors will overuse it, and because bacteria have to survive – they are very very clever – they will become resistant to it”.
Sources
Andrew Henderson, Graeme R Nimmo, Control of healthcare- and community-associated MRSA: recent progress and persisting challenges, British Medical Bulletin, Volume 125, Issue 1, March 2018, Pages 25–41, https://doi.org/10.1093/bmb/ldx046
Chambers, H., DeLeo, F. Waves of resistance: Staphylococcus aureus in the antibiotic era. Nat Rev Microbiol 7, 629–641 (2009). https://doi.org/10.1038/nrmicro2200
Chatrchai Watanakunakorn, Mode of action and in-vitro activity of vancomycin , Journal of Antimicrobial Chemotherapy, Volume 14, Issue suppl_D, 1984, Pages 7–18, https://doi.org/10.1093/jac/14.suppl_D.7
https://www.cdc.gov/hai/organisms/staph.html
https://www.imperial.ac.uk/news/189049/sir-alexander-fleming-knew-1936-bacteria/
Levine, Donald. (2006). Vancomycin: A History. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 42 Suppl 1. S5-12. 10.1086/491709.
Tan, Siang & Tatsumura, Yvonne. (2015). Alexander Fleming (1881-1955): Discoverer of penicillin. Singapore medical journal. 56. 366-7. 10.11622/smedj.2015105.
Thank you, science 