Preprint: The porin MspA is a phage-specific determinant of mycobacteriophage infection

Mycobacteriophages are increasingly considered as therapeutics for mycobacterial infections, yet we still know relatively little about which host factors determine whether a given phage can successfully infect its target. In this preprint, led by Doyeon Kim in the lab, we asked this question systematically.

Using a genome-wide CRISPRi screen in Mycobacterium smegmatis challenged with the phage BPsΔ33HTH HRM10, we found the outer membrane porin genes mspA and mspC among the strongest hits, while their close paralogs mspB and mspD were not. Deleting either gene reduced plaque formation and produced smaller, more turbid plaques, with the mspA deletion showing the stronger phenotype.

Testing a panel of 25 mycobacteriophages against the ΔmspA strain revealed that the requirement is phage-specific: 11 phages showed either a greater than tenfold drop in titer or no discrete plaques, while the remainder were largely unaffected. Porins therefore join cell envelope lipids and glycolipids as determinants of mycobacteriophage infection, and knowing which phages depend on them may help in rationally designing phage cocktails.

This work was carried out together with Pierre Santucci and Mickael Maziero (LISM, Aix-Marseille Université/CNRS) and the Rock lab at Rockefeller University.

Read the preprint: The porin MspA is a phage-specific determinant of mycobacteriophage infection →