Antibiotics and phages drive region-specific diversity of OmpK36 in <i>Klebsiella pneumoniae</i>

Porins are outer membrane proteins involved in the passive diffusion into the periplasm of substrates such as nutrients. They are also a major route for antibiotics. Mutations in the main porins of <i>K. pneumoniae</i>, OmpK35 and OmpK36, have been described and mainly lead to disruption of the former and a pore size reduction of the latter through amino acid insertion in the constriction loop. <i>ompK36</i> mutations are clinically significant, with a reduction in susceptibility to β-lactams, particularly when strains also produce a carbapenemase. However, little is known about the overall diversity of OmpK36. Through large-scale genome analysis and experimental work, we sought to decipher the selective pressures that shape the diversity of this protein. Our results suggest that antibiotics are not the main driver of OmpK36 diversity at the level of the entire protein sequence and that phages can instead rapidly select variations in the extracellular loops.