Mycobacterium smegmatis – Why are we hunting for phages that infect this species of bacteria?

If you’ve read any of the other posts on this Phage Hunt NZ blog, you may already know a little about the struggles us hunters go through to find phages. The ultimate aim of our hunt is to discover brand new types of bacteriophages (viruses that infect and usually kill bacteria), in an effort to not only contribute to the world’s collective knowledge of these genetic parasites but also in an attempt to understand our local ecosystems. As microscopically tiny as viruses are, they play a huge role in the microecology of our world. The epic unseen struggle between phages and the bacteria they parasitise, drives a fierce cycle of coevolution which can have big impacts on whole ecologies. This is a very interesting field of research, and despite being discovered more than 100 years ago, with new advances in genetic technology there is now renewed interest in phages.

 

Phages are one of the most abundant organisms on the planet so would think this phage hunt business would be pretty straightforward, right? [1] Not quite. When we search for evidence of phages in our environmental samples, we use a method that filters out bacteria and other large organisms and the leftover solution consisting of phage (hopefully) and added nutrients necessary for phage replication is poured over a lawn of bacteria growing on agar – consisting of one strain of bacteria. In the case of the Phage Hunt New Zealand group the bacterial host we used was Mycobacterium smegmatis, a fairly common soil bacteria. If phages are present and manage to infect the bacteria then small clearances where phages have killed the bacteria, called plaques will form.

 

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Plaques of my phage Daegal

This first step is where we encounter problems. The issue is that phages are very specific in what bacteria they can infect, with many having host ranges of only a few strains of bacteria. Though there will very likely be many thousands, millions or even billions of phage particles in one small sample, this method will only screen for those that infect the specific bacteria you used to make the bacterial lawn. Furthermore, the conditions which these new strains of phage need to survive may be very different from what is expected, and even if there are many phages present that infect your strain of bacteria the process of extracting them from your samples may be enough to destroy them.

Why not introduce your samples to other types of bacteria? If M. smegmatis phages are so hard to find, why bother sticking with it? The answer is pretty complex and I could probably spend forever discussing it but for now I’ll just give a brief introduction to M. smegmatis and give some reasons as to why we use it.

 

M. smegmatis is a fast growing growing species and this, combined with its comparative non-pathogenicity makes it a very useful substitute for studying the earlier mentioned pathogenic bacteria that it shares many similarities with. [2] Why should this matter to us?

 

Tuberculosis is a serious and potentially deadly disease caused by M. tuberculosis bacteria infecting humans. It spreads through inhalation of the bacteria and can easily spread through populations. It is still a huge issue in many developing countries, and even in New Zealand there are approximately 300 cases of TB diagnosed each year. Though healthy adults infected with the bacteria rarely experience any adverse effects or even show symptoms, in those with compromised or vulnerable immune systems like babies, the elderly or those with AIDS the disease can cause serious illness and if left untreated often results in death. [3]

Luckily an intensive course of antibiotics is usually very effective in treating TB and mortality due to the disease has been reduced significantly. [3] The disease that once claimed entire families is all but nonexistent in the minds of many New Zealanders.

 

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Graph showing Tuberculosis mortality among HIV-positive people. (Source: https://www.undispatch.com/map-day-people-die-tuberculosis/)

 

In recent times, the issue of antibiotic resistance has become a real concern. Overuse of antibiotics and a lack of progress in finding new antibiotics has meant that strains of bacteria have evolved that are immune to treatment. These strains threaten to plunge us back into the pre-antibiotic era. 480, 000 people globally are infected with multi-drug resistant TB every year and this number will likely increase. [4]

Antibiotic resistance is causing many to turn to phage therapy, an alternative to antibiotics that involves exposing patients to phages that are specific to the bacteria causing the infection. The phages only infect and kill these target bacteria, leaving the rest of the helpful bacteria in the patient’s bacteria unharmed. [1]

The hope is that along the way in finding new strains of M. smegmatis bacteriophage, we could find phages that infect M. tuberculosis as well and these could potentially be used in phage therapy to treat cases of antibiotic resistant tuberculosis. The development of new medical treatments is a long and arduous process and though not every phage has the chops to be the downfall of tuberculosis, by discovering and studying new that infect M. smegmatis phages we can know that not only are we contributing to scientific progression but possibly to a happier and healthier planet.

PHAGE

References:

 

  1. Bacteriophage therapy treats patient near death with MDR Acinetobacter baumannii. (2017, April 25). Outbreak News Today. Retrieved from http://outbreaknewstoday.com/bacteriophage-therapy-treats-patient-near-death-mdr-acinetobacter-baumannii-45488/

 

  1. Mycobacterium smegmatis. (Last edited 2011, April 22). Microbewiki. https://microbewiki.kenyon.edu/index.php/Mycobacterium_smegmatis

 

  1. Tuberculosis disease. (Last updated 2016, September 9). Ministry of Health. http://www.health.govt.nz/your-health/conditions-and-treatments/diseases-and-illnesses/tuberculosis-disease

 

  1. Antimicrobial Resistance. (Last updated 2016, September). World Health Organisation. http://www.who.int/mediacentre/factsheets/fs194/en/

 

 

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