Spotlight on Chemists

Irene Chen: Bacteriophages and Phage Therapy

Bacteriophage

The Post-Antibiotic Era & Bacteriophages

The age of antibiotics began with the introduction of penicillin, hailed as a medical miracle that combated an ever-present risk of fatal infections. For more than a century, antibiotics have been the major force of action against bacterial diseases. However, recent studies show a rapid emergence of multidrug-resistant (MDR) bacteria – “superbugs” that are resistant to several types of antibiotics. This presents a worldwide crisis: antibiotics are highly important and widespread drugs in modern medicine, and their rising inefficacy against infections is an urgent global public health threat, killing at least 1.27 million people worldwide and associated with nearly 5 million deaths in 2019 [1]. The imminent AMR (antimicrobial resistance) crisis ushers in a need to develop new antibiotics and therapeutics. Prior to the discovery of antibiotics, bacteriophage therapy – what Dr. Irene Chen studies in her lab at UCLA – was widely enforced to combat bacterial infections, before being sidelined mainly due to the discovery of penicillin in 1940 [2].

Bacteriophages are viruses that specifically infect bacteria, and are recognized as the most abundant biological entities on the planet. The lytic life cycle of phages (see below) begins with the attachment of the bacteriophage tail to the cell wall of the host bacterium. The phage then “drills” a hole in the bacterium’s cell wall and replicates using the bacterium’s metabolic machinery. The process ends when the phage finally ruptures the wall completely (called lysis) [3]. Phage therapy presents a potent and effective alternative to antibiotics in the age of multidrug resistance, a possibility that Dr. Irene Chen explores.

The Lytic Life Cycle

The lytic life cycle may be divided into five distinct stages. The first stage is adsorption, which refers to the bacteriophage’s accumulation at the bacteria’s surface. Attachment sites on the bacteriophage adsorb to receptor sites on the host bacterium – most bacteriophages adsorb to the cell wall of the bacterium [5]. The next stage is penetration, wherein the bacteriophage enzyme “drills a hole” into the bacterial cell wall and injects its genome (genetic information) in the cell cytoplasm [4]. In the replication stage, enzymes created by the bacteriophage genome shut down the host’s macromolecular (protein, RNA, DNA) synthesis. The bacteriophage replicates its genome and uses the bacterium’s metabolic machinery to produce bacteriophage structural components [5]. Through maturation, these phage parts assemble around the genome and finally release through lysis, i.e., the breaking down of the membrane of the bacterium. 

Phage Therapy

Scientific probing into phage therapy continues and poses promising results. One method consists of using gold nanoparticles that are delivered into the bacterium by the phages and consequently kill it due to overheating. However, while using bacteriophages as a means to combat bacterial infections may seem obvious, in practice, phage therapy remains imprecise due to some of its disadvantages.

One of these is host specificity – phages are highly specific for the receptors on the host’s cell wall and may not be compatible with all species and strains. Making a ‘broad host-range phage’ that can recognise different strains is an effective solution that remains under experimentation. Another issue is that some naturally-occurring phages are detrimental to human health and can even make the infection more difficult to treat [4]. Understanding their complex working is a preliminary step towards designing synthetic phages that can overcome the limitations of phage therapy and potentially lead to defeating MDR bacteria [2]. 

Learn More

If you’d like to hear more about this fascinating biological agent and one of its pioneer researchers, visit us on Spotify to listen to our ChemTalk podcast with Dr. Irene Chen, assistant professor and chemist at the University of California, Los Angeles, to discuss ongoing research into phage therapy, the challenges along the way, and what her advice is for current grad students and high-schoolers who aspire to pursue a career in STEM. 

Find the ChemTalk podcast here: https://open.spotify.com/episode/7j447MqGK0EPm6HsVAwGqD

Works Cited

[1] “About Antimicrobial Resistance.” Centers for Disease Control and Prevention, 5 October 2022. 

https://www.cdc.gov/drugresistance/about.html

[2] Orzechowska, B., & Mohammed, M. (2019). The War between Bacteria and Bacteriophages. In  (Ed.), Growing and Handling of Bacterial Cultures. IntechOpen. 

[3] Shen, C. Zhang, Y. (2022). Introductory Microbiology Lab Skills and Techniques in Food Science. Academic Press. 

[4] Chen, Irene. Personal Interview. Conducted by Roxanne Salkeld. 4 September 2022. 

[5] The Lytic Life Cycle of Bacteriophages. (2022, April 9). Community College of Baltimore Country (Cantonsville). https://bio.libretexts.org/@go/page/3244