Phage Resistance in Streptococcus pneumoniae

From MicrobeWiki, the student-edited microbiology resource

Introduction

Bacteriophages are viruses that infect and replicate within bacteria and archaea. They can be used in phage therapy, a therapeutic treatment used to fight bacterial infections, through specialization and differentiation and are a promising solution to the growing threat of antibacterial resistance. [1]

Streptococcus pneumoniae is responsible for a myriad of bacterial infections such as pneumonia, meningitis, sinusitis, otitis media, and bacteremia. With the variety of infections that this bacterium causes, it is evident that specialized phage therapy provides a new solution to an old culprit. [2]

Streptococcus pneumoniae bacteria by the NFID[1].

Genetics: Mechanisms

The main culprit of phage resistance in bacteria are hypermutable loci which are locations on the genome that exhibit unusually high levels of mutation. Even if there is not complete phage resistance amongst a colony, even limited numbers of resistant cells severely limit the spread of phages throughout the aggregate (Front Microbiology). In some cases, phage resistance may be deemed advantageous for the host: certain phage resistance mutants may have lessened symptom severity as seen in the De Angelis et. Al 2021 study.

The mechanisms of phage resistance in bacterial cells work as such: “receptor blocking, extracellular matrix production, and competitive inhibitor production” (Nature Reviews Microbiology)”. It has been supported that R6-SOCPR and R6-DP1R are genes that are responsible for phage resistance within the S. pneumoniae genome. [3]

It is interesting to note that typical mechanisms of phage therapy involve lytic phages in a mixture referred to as a “phage cocktail”. Among the variants of S. pneumoniae, there is a relatively even distribution between lysogenic and lytic varieties thus proving further research in phage therapy among lysogenic species. One double-edged sword of phage therapy is the relationship between the specificity of the reacting phage to achieve a desired effect. It can either be a perfect match and work effectively or there can be resistance or complete inefficacy.


Illustrated mechanism of phage resistance in bacteria by Nature Microbiology[2].

Microbiome

The microbiomes of Streptococcus pneumoniae that are primarily studied are located in the nasal cavity and the lungs. In the nasal cavity, there are various interactions between healthy and deleterious microbiota– these microbes include: Staphylococcus epidermidis, Moraxella, Haemophilus, Corynebacterium, Dolosigranulum, and Corynebacterium propinquum. [4]

When looking at the efficacy of phage therapy against S. pneumoniae, it is also important to think of synergistic effects towards the microbiome. When phage therapy is utilized in combination with other treatment methods, such as standard antibiotics, there may be higher efficacy.

Conclusion

The continued research of bacteriophages as a treatment against Streptococcus pneumoniae is crucial in lessening the mortality rate from pneumonia and other meningococcal illnesses. As the field in phage therapy and the effects of phage resistance continues to grow, the knowledge will spread to ameliorate the human condition through the catalysis of medicine. With the mortality rate of Streptococcus pneumoniae related infections being as high as 30% in certain regions, phage therapy and combatting phage resistance in appropriate cases provides a groundbreaking opportunity to impart change.

References

[5] [6] [7] [8] [9] Cite error: Closing </ref> missing for <ref> tag Henrici De Angelis, L., Poerio, N., Di Pilato, V., De Santis, F., Antonelli, A., Thaller, M. C., Fraziano, M., Rossolini, G. M., & D'Andrea, M. M. (2021). Phage Resistance Is Associated with Decreased Virulence in KPC-Producing Klebsiella pneumoniae of the Clonal Group 258 Clade II Lineage. Microorganisms, 9(4), 762. https://doi.org/10.3390/microorganisms9040762.</ref>

  1. ↑ [Dietl, Beatriz, Desirée Henares, Lucía Boix-Palop, Carmen Muñoz-Almagro, Javier Garau, and Esther Calbo. “Related Factors to Streptococcus Pneumoniae Invasive Infection and Clinical Manifestations: The Potential Role of Nasopharyngeal Microbiome.” Frontiers. Frontiers, January 1, 2021. https://www.frontiersin.org/articles/10.3389/fmed.2021.650271/full]
  2. ↑ [Borges, Adair L. “How to Train Your Bacteriophage.” PNAS. National Academy of Sciences, July 13, 2021. https://www.pnas.org/content/118/28/e2109434118.]
  3. ↑ [Immunity against Bacteriophage Invasion of Bacterial Meta-Populations.” Frontiers. Frontiers, January 1, 2021. https://www.frontiersin.org/articles/10.3389/fmicb.2019.01473/full.]
  4. ↑ [Lin, Derek M, Britt Koskella, and Henry C Lin. “Phage Therapy: An Alternative to Antibiotics in the Age of Multi-Drug Resistance.” World journal of gastrointestinal pharmacology and therapeutics. Baishideng Publishing Group Inc, August 6, 2017. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5547374/.]
  5. ↑ Borges, Adair L. “How to Train Your Bacteriophage.” PNAS. National Academy of Sciences, July 13, 2021. https://www.pnas.org/content/118/28/e2109434118.
  6. ↑ de Steenhuijsen Piters, Wouter A. A., Simon P. Jochems, Elena Mitsi, Jamie Rylance, Sherin Pojar, Elissavet Nikolaou, Esther L. German, et al. “Interaction between the Nasal Microbiota and S. Pneumoniae in the Context of Live-Attenuated Influenza Vaccine.” Nature News. Nature Publishing Group, July 5, 2019. https://www.nature.com/articles/s41467-019-10814-9.
  7. ↑ Dietl, Beatriz, Desirée Henares, Lucía Boix-Palop, Carmen Muñoz-Almagro, Javier Garau, and Esther Calbo. “Related Factors to Streptococcus Pneumoniae Invasive Infection and Clinical Manifestations: The Potential Role of Nasopharyngeal Microbiome.” Frontiers. Frontiers, January 1, 2021. https://www.frontiersin.org/articles/10.3389/fmed.2021.650271/full.
  8. ↑ Labrie, Simon J., Julie E. Samson, and Sylvain Moineau. “Bacteriophage Resistance Mechanisms.” Nature News. Nature Publishing Group, March 29, 2010. https://www.nature.com/articles/nrmicro2315.
  9. ↑ Lin, Derek M, Britt Koskella, and Henry C Lin. “Phage Therapy: An Alternative to Antibiotics in the Age of Multi-Drug Resistance.” World journal of gastrointestinal pharmacology and therapeutics. Baishideng Publishing Group Inc, August 6, 2017. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5547374/.
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