Bacteriophages and their Effectiveness as Antimicrobials Sergio Toolasprashad, Adam Desouky, & Sharon Phillips Ph.D Hofstra University Abstract
Purpose
Discussion
- Research on the bacteriophage is becoming more prevalent with the medical community.
- Test effectiveness of phages against Streptococcus pneumoniae
- The test allows quick multiplication and spread of S. pneumoniae to occur. Natural infections in other animals, including humans, however, would likely be much slower and therefore easier to treat with possible higher rates of survival.
- Bacteria have been evolving against antibiotics throughout history, thus further research on this topic is becoming more necessary. - Due to what they can achieve, scientists began to use these viruses as experimental therapeutics against diseases. - Minimal research currently exists on the effectiveness of phages on human diseases caused by the Streptococcus pneumoniae species of bacteria. - We propose a method in testing and displaying the possible effectiveness of bacteriophages against the infectious bacteria (Streptococcus pneumoniae) via a mouse model.
Background - The bacteriophage, also known as phage, can be considered the virus of bacteria and is the most common organism on the planet (Suttle, C. A., 2005). It infects its bacterial hosts via a lytic/virulent life cycle. Towards the end of this cycle, newly formed viruses can carry either viral or bacterial DNA. To reduce bacterial DNA recombination, bacteriophage therapy was introduced. - This method of therapy is critical to today’s world in lieu of the increase in multi-drug resistant bacteria that have evolved with history (Nikolich, M.P. and Fillipov, A.A., 2020) and with the little development in antibiotics as of recent (Neu, H.C., 1992 & World Health Organization, 2017). - Essentially, these phages hijack the transcription, translation, and replication machinery of the host to replicate its own DNA and protein composition and ultimately lyse its host while enabling the re-infection of a multitude of other hosts (Sadava D., Hillis D.M., Heller H.C., Berenbaum M.R., 2014) - When considering the human response, the phages are weak immunogens and generally have weak side-effects (Nikolich, M.P. and Fillipov, A.A., 2020). - Phages utilize mechanisms specific from antibiotics to affect bacterial hosts, enabling the development of antibiotic-phage synergies with treatment (Nikolich, M.P. and Fillipov, A.A., 2020).
- Determine reliability in using phages as antimicrobial therapeutics to combat drug resistant bacteria.
Methods - Test effectiveness of MM1 phages against Streptococcus pneumoniae bacteria through mouse model using adult female BALB/c mice.
- Because those naturally occurring infections require longer treatments, this means it could encourage the emergence of phage resistant bacteria. However, phages also have the ability to evolve with their hosts making it harder for their hosts to become resistant to the phages - More species of animals should be considered to ultimately relate the effectiveness of the MM1 phage against S. pneumoniae bacteria in humans.
- Infect five separate groups of mice with bacteria via intraperitoneal (i.p.) injection and then immediately administer phage cocktail containing MM1 phages via intramuscular (i.m.), i.p., and subcutaneous (s.c.) injections. - Each group of mice will receive phage administration via one of the three injection pathways. - The fourth group of bacteria-infected mice will not be administered any phages and the fifth group will only be administered MM1 phages via i.p. without any exposure to the bacteria. - Populations will all be comprised of the same species and number of mice. Mortality rates of each group will be recorded at several times post inoculation/infection.
Data Analysis - Fisher’s exact test can be used to identify possible relationships between two variables: effectiveness of the bacteriophages in combating the bacterial infection (independent variable), and mortality rates of each treatment group (dependent variable). - Statview for Windows, or SAS Institute softwares can be used apply FIsher’s exact test to the quantitative analysis of the resulting data.
References Neu H.C. (1992). The Crisis in Antibiotic Resistance. Science, 257(5073), 1064–1073. Nikolich, M.P.; Filippov, A.A. (2020). Bacteriophage Therapy: Developments and Directions. Antibiotics, 9(3), 135. Sadava D., Hillis D.M., Heller H.C., Berenbaum M.R. (2014) Life: The science of Biology, 10th edition. W.H. Freeman, 813-814. Suttle, C. A. (2005). Viruses in the sea. Nature 437, 356–361. World Health Organization. (2017). Antibacterial agents in clinical development: an analysis of the antibacterial clinical development pipeline, including tuberculosis, World Health Organization, (No.WHO/EMP/IAU/2017.11)