Periodic Reporting for period 3 - CoPathoPhage (Pathogen-phage cooperation during mammalian infection)
Okres sprawozdawczy: 2022-10-01 do 2024-03-31
Exploring other phage remnant elements of Lm, we investigated a conserved genetic locus that contains phage related genes. We found these genes to be transcriptionally upregulated during Lm’s growth in intracellular conditions. We found that this element encodes a metzincin and TIMP-like proteins, that interact in a manner rarely recorded—the TIMP-like lipoprotein is adapted to be cleaved and released to the culture medium by the metzincin. The release of the TIMP-like leads to changes in the bacterial cell morphology and to an increase in bacterial sensitivity to phage lysins and drugs that target the cell wall. This locus may therefore have therapeutic use: to make otherwise resistant bacteria more susceptible to lytic factors and compounds, such as penicillin and phage-encoded lysins, which play an important role in phage therapy.
By the end of the project we expect to uncover additional determinants and mechanisms that are involved in the regulation of the phage elements, and make a true progress in understanding the biological impact of inter-phage cross-talk in supporting bacterial virulence.