Role of prophages in the spread of antiviral resistance in Pseudomonas aeruginosa

Almost all bacteria contain mobile genetic elements (MGE), which often carry adaptive genes such as antimicrobial resistance (AMR) and virulence genes and that are important actors of horizontal gene transfer among bacteria. These elements include phages (viruses that infect bacteria) and conjugative elements, as well as satellites and mobilizable elements which mobility rely on hijacking the formers. Because MGE can be costly, or even lethal in the case of phages, bacteria have evolved defence systems, such as restriction/modification or CRISPR-Cas systems. By shaping the flux of MGE, these defence systems ultimately determine how AMR and virulence genes spread in bacterial populations. Recent studies discovered an impressive number of new defence systems and revealed that defence genes are very mobile themselves, as they are often encoded on MGE. In particular, temperate phages, which can lay dormant integrated in bacterial chromosomes as prophages, were found to encode many defence systems that protect the host cell against infection by other phages. Because they can drive the mobility of defence genes, temperate phages may be important vehicles of the spread of resistance against other MGE, especially against virulent phages, but this has been poorly explored. We aim to provide key functional insights on the role of temperate phages in the emergence and spread of phage resistance in the opportunistic pathogen Pseudomonas aeruginosa. Our findings will be useful for the development of phage therapy, a strong therapeutic alternative to antibiotics, which also faces the threat of rapid spread of phage resistance in bacteria. More largely, studying how the dynamical network of bacterial defence genes shapes the flux of MGE will help to better understand how virulence genes, AMR and phage resistance genes are exchanged and spread amongst bacteria.

 

Publications:

  1. Schiettekatte O, Beurrier E, De Sordi L, Chevallereau A†. (2023) “French Phage Network” Annual Conference—Seventh Meeting Report. Viruses
  2. Pons B, van Houte S, Westra E, Chevallereau A†. (2023) Ecology and Evolution of Phages Encoding Anti-Crispr Proteins. Journal of Molecular Biology (review)
  3. Chevallereau A, Pons B, van Houte S, Westra E. (2021) Interactions and evolution of bacteria and bacteriophages in natural communities. Nature Reviews Microbiology (review)
  4. Rollie C†*, Chevallereau A†*, Watson B, et al. (2020) Imperfect targeting of phages drives loss of CRISPR-Cas systems from bacteria. Nature.
  5. Chevallereau A†, Meaden S, Fradet O, et al. (2020) Exploitation of cooperative behaviours of anti-CRISPR phages. Cell Host & Microbes.
  6. Dufour N, Delattre R, Chevallereau A, et al. (2019) Phage therapy of pneumonia is not associated with an over stimulation of the inflammatory response compared to antibiotic treatment in mice. Antimicrobial Agents and Chemotherapy
  7. Chevallereau A*, Meaden S*, van Houte S*, et al. (2019) The effect of host mutation rate on the evolution of CRISPR-Cas adaptive immunity. Philosophical Transactions B.
  8. Landsberger M, Gandon S, Meaden S, Rollie C, Chevallereau A, et al. (2018). Anti-CRISPR phages cooperate to overcome CRISPR-Cas immunity. Cell.
  9. Blasdel BG*, Chevallereau A*, Monot M, et al. (2017). Comparative transcriptomics analyses reveal the conservation of an ancestral infectious strategy in two bacteriophage genera. The ISME journal.
  10. Chevallereau A*, Blasdel BG*, De Smet J, et al. (2016) Next-Generation “-omics” approaches reveal a massive alteration of host RNA metabolism during bacteriophage infection of Pseudomonas aeruginosa. PLOS Genetics.
  11. Henry M, Bobay LM, Chevallereau A, et al. (2015) The search for therapeutic bacteriophages uncovers one new subfamily and two new genera of Pseudomonas-infecting Myoviridae. PLOS One.

Preprints:

  1. Maestri A, Pursey E, Chong C, Pons B, Gandon S, Custodio R, Chisnall M, Grasso A, Paterson S, Baker K, van Houte S, Chevallereau A*, Westra E*. (2023) Bacterial defences interact synergistically by disrupting phage cooperation. bioRxiv https://doi.org/10.1101/2023.03.30.534895 (submitted)
  2. Blasdel BG, Ceyssens P-J, Chevallereau A, et al. (2018) Comparative transcriptomics reveals a conserved Bacterial Adaptive Phage Response (BAPR) to viral predation. bioRxiv. https://doi.org/10.1101/248849