13. Juli 2023 Tobias Hohenauer

Hello and welcome back!

This is the second installment of the Lab Journal quick facts!

I wish I could have stuck to my plan of publishing one of these per quarter but the last three months were so busy that I could only finish working on the phage therapy topic today.

Please have a look around and let me know what you think about phage therapy or the Lab Journal quick facts in the comments!

Quick facts about phage therapy.

The problem:

Multiresistant bacteria have emerged due to the overuse and misuse of antibiotics in both humans and animals. Through genetic mutations or the acquisition of resistance genes from other bacteria, these pathogens have developed mechanisms to neutralize the effects of antibiotics.

As a result, infections caused by multiresistant bacteria are difficult to treat and can lead to increased morbidity, mortality, and healthcare costs.

A solution:

Phage therapy is a type of treatment that uses bacteriophages, which are viruses that infect and kill bacteria, to treat bacterial infections [1]. The principles of phage therapy involve identifying and isolating specific phages that can target and destroy the bacterial strains causing the infection. Phage therapy is a potential alternative to traditional antibiotic treatments that have become increasingly ineffective due to bacterial resistance [2].

The purpose of phage therapy is to provide a targeted and precise treatment for bacterial infections, reducing the need for broad-spectrum antibiotics that can harm beneficial bacteria and promote the development of antibiotic-resistant strains [2]. Phage therapy can also be used to treat chronic infections and to prevent the spread of antibiotic-resistant bacteria [1].

The benefits of phage therapy include its specificity, efficacy, and safety [2]. Phages only target specific bacteria, so they do not harm other cells or beneficial bacteria. They can also rapidly replicate and adapt to the evolving bacterial populations, making them potentially effective against antibiotic-resistant strains. Additionally, phages have a long history of safe use in Eastern Europe, where they have been used to treat bacterial infections for decades [2].

Recent findings have demonstrated the potential of phage therapy for treating a variety of bacterial infections, including urinary tract infections, wound infections, and respiratory tract infections [1]. Some studies have also explored the use of phage therapy for treating infections caused by multidrug-resistant bacteria, such as Pseudomonas aeruginosa and Acinetobacter baumannii [3].

To be effective as a therapy, phages should be able to effectively target and eliminate bacteria while minimizing any negative impact on their surroundings. This can be achieved by ensuring that the phages are obligately lytic, can withstand standard storage conditions and temperatures, undergo rigorous efficacy and safety testing, and ideally, have their entire genome sequenced to confirm the absence of any harmful genes such as toxins.

The main differences between lytic and lysogenic phages (from refs [5]-[8]):

1 Lytic phages: Lytic phages follow a reproductive cycle that ultimately leads to the lysis (bursting) of the host bacterial cell. The steps of the lytic cycle are attachment, penetration, transcription, replication, assembly, and lysis.

2 Lysogenic phages: Lysogenic phages, on the other hand, integrate their DNA into the host genome and replicate along with it, without causing cell lysis. The lysogenic cycle consists of attachment, penetration, integration, replication, and excision.

3 Impact on host cell: Lytic phages cause the host cell to lyse and release newly formed viral particles, which can infect other cells. Lysogenic phages integrate their genetic material into the host cell’s genome, and the host cell reproduces normally until an event triggers the phage to switch to the lytic cycle.

4 Infection efficiency: Lytic phages have a high infection efficiency and produce many progeny phages quickly, while lysogenic phages have a low infection efficiency and typically produce fewer progeny phages .

5 Evolution: Lytic phages evolve to maximize the efficiency of host cell lysis and viral replication, while lysogenic phages evolve to maintain their integration within the host cell genome and minimize any negative effects on host cell survival.

Addressing the problem of multiresistant bacteria requires a multifaceted approach. This includes implementing robust infection control measures, promoting the responsible use of antibiotics, developing new antibiotics, and researching alternative treatment strategies such as phage therapy and immunotherapy.

References:

[1] Fish, R., Kutter, E., Wheat, G., Blasdel, B., Kutateladze, M., & Kuhl, S. (2016). Bacteriophage treatment of intransigent diabetic toe ulcers: a case series. Journal of wound care, 25(Sup7), S27-S33.
[2] Golkar, Z., Bagasra, O., & Pace, D. G. (2014). Bacteriophage therapy: a potential solution for the antibiotic resistance crisis. Journal of infection and public health, 7(4), 349-354.
[3] Torres-Barceló, C. (2018). The disparate effects of bacteriophages on antibiotic-resistant bacteria. Emerging microbes & infections, 7(1), 168.
[4] „Bacteriophages and Their Role in Food Safety“ by Annika Gillis and Jean-Paul Noben. 2014. Food Safety Magazine. https://www.foodsafetymagazine.com/magazine-archive1/augustseptember-2014/bacteriophages-and-their-role-in-food-safety/
[5] „Lysogenic Cycle of Bacteriophage Lambda“ by Stephanie Garcia, Arjun Raj, and Adam P. Arkin. 2013. Cold Spring Harbor Perspectives in Biology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753991/

[6] „The Life Cycle of Bacteriophage T4“ by John F. Kutter, Elizabeth A. Kutter, and Martha M. Carlson. 2010. The Bacteriophages. https://www.ncbi.nlm.nih.gov/books/NBK14316/
[7] „Lytic and lysogenic cycle of phage“ by Akash Singh and Renu Singh. 2018. International Journal of Current Microbiology and Applied Sciences. https://www.ijcmas.com/7-2-2018/Akash%20Singh%20and%20Renu%20Singh.pdf
[8] „Bacteriophage Evolution“ by Andrew M. Kropinski. 2018. The Bacteriophages. https://www.ncbi.nlm.nih.gov/books/NBK534247/

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