How viruses can help us fight against antibiotic-resistant bacteria?

Pierre Marcoux graduated in 1999 from ESPCI (Ecole Supérieure de Physique et de Chimie Industrielles de la Ville de Paris). Initially, his research interest focused on the surface chemistry of nanomaterials, such as carbon nanotubes or fullerenes. He switched from nano to microscale in 2006 when he joined LETI (Laboratoire d’électronique et de Technologie de l’Information) at CEA, Grenoble to work on new techniques for the diagnosis of bacterial infectious diseases. He is especially interested in optical techniques as they are non-invasive, label-free, and better adapted to automation. 

 

In 1917, Felix d’Hérelle, a French-Canadian microbiologist observed «holes» in a culture of dysentery bacteria. These holes were the sign of a bacteria destruction which is called the “lysis”1. Though Twort, a British scientist, had made similar observations a few years before, d’Hérelle was the first to interpret the lysis as the presence of an “invisible microbe with antagonistic properties against” bacteria that would later be called “bacteriophages” (literally “eater of bacteria”).

The bacteriophages remained invisible for more than 20 years after d’Hérelle observations because of the lack of technological tools to image them. It is only in 1940, after the invention of electron microscopy, that Helmut Ruska, a German scientist, published the first image of a bacteriophage.

After a century of research, scientists were able to discover more about bacteriophages and their mechanism. It is now known that phages are viruses which are estimated to be the most abundant organisms on the planet with a number of 103. They replicate by infecting and lysing bacteria making them natural antibacterial agent suitable for therapeutic use.

D’Hérelle was the first in 1919 to use bacteriophages to successfully cure children with a bacterial infection in Paris2. The following years, phage therapy was again used to treat patient with bacterial infection but because of the growing demands in anti-bacterial treatments during World War II, the use of phages as therapeutics agent was dropped in western countries for antibiotics, as they were easier to use (they have indeed a much broader activity spectrum than phages). Nonetheless, phage therapy has never been completely abandoned in USSR countries, such as Poland and Georgia, which lacked economical means to get antibiotics manufacturing facilities.

However, the first resistance to antibiotics appeared only a few years after their introduction on the market and because of the extensive use of antibiotics in the medical and the agricultural field, the apparition of drug-resistant bacteria increased over the last decades.

If nothing is done, it is estimated that by 2050, 10 million people will die every year due to infection by drug-resistant bacteria. Click To Tweet

In November 2015, Chinese scientists published about bacteria resistance to colistin, known as “the last resort antibiotic”. In the months that followed, the resistance spread worldwide3 raising concern about a potential return to a post-antibiotic era in which even minor bacterial infections could kill. If nothing is done, it is estimated that by 2050, 10 million people will die every year due to infection by drug-resistant bacteria4.

These alarming observations along with the insufficient supply of new antibiotics contributed to the renewed interest in phage therapy.

However, contrary to antibiotics, bacteriophages have a narrow and specific antimicrobial activity. Indeed, an antibiotic can be effective against several types of bacteria, whereas a given phage can only be effective against certain members of the same bacterial species. Therefore, to get the most effective therapeutic effect and prevent an outbreak of phage resistant bacteria, it is necessary to set up reliable diagnostic tests.

When someone is treated through antibiotherapy, a sample of the pathogen bacteria from the patient is tested to assess the susceptibility of the bacteria to a given group of antibiotics. Most of the time, these tests are run through an automated platform.

Similar tests could be applied to phage therapy. Some manual protocols already exist to assess the efficacy of different phages on a given bacteria, but they require skilled microbiologists and are time-consuming. Therefore, just like antibiotic susceptibility testing, the phage susceptibility testing will have to comply with the increasing automation of clinical microbiology labs and results should be provided as quickly as possible to maximize the chance of a therapeutic success.

In our laboratory, we develop devices and methods for analyzing the specific action of phages on bacteria. Our objective is to develop innovative ways of performing phage susceptibility testing, with cheaper, faster and easier tests. These viruses have saved lives and it’s highly likely that one day they will be as common as antibiotics!

 

References

  1. D’Herelle, F. On an invisible microbe antagonistic toward dysenteric bacilli: brief note by Mr. F. D’Herelle, presented by Mr. Roux. 1917. Res. Microbiol. 158, 553–554 (2007).
  2. Abedon, S. T., Kuhl, S. J., Blasdel, B. G. & Kutter, E. M. Phage treatment of human infections. Bacteriophage 1, 66–85 (2011).
  3. Reardon, S. Resistance to last-ditch antibiotic has spread farther than anticipated. Nat. News doi:10.1038/nature.2017.22140
  4. O’Neill, J. Tackling drug-resistant infections globally : final report and recommendations. (2016). Available at: https://amr-review.org/sites/default/files/160518_Final%20paper_with%20cover.pdf. (Accessed: 10th April 2018)

Opinions in this blog post are that of the author, and not necessarily that of Hindawi. The profile photo was provided by Pierre Marcoux. The text in this blog post is by Pierre Marcoux and is distributed under the Creative Commons Attribution License (CC-BY). Illustration by Hindawi and is also CC-BY.