Antibiotic uptake into gram-negative bacteria is mainly due to their passive diffusion porins, which are general-diffusion channel-proteins found in their outer-membrane. An ever-increasing number of MDR clinical isolates are reported in which an outer membrane barrier of low permeability is observed. Understanding the structural basis for a decreased antibiotic uptake is therefore determinant in the quest for new, more efficient antimicrobial agents...We have solved the crystalline structures of the two porins of Providencia stuartii, Omp-Pst1 and OmpPst2, from the ATCC strain. Providencia stuartii is a bacterium displaying a stringent multidrug resistance phenotype and that is involved in bacteriuria in patients with long-term indwelling catheters. The two porins display inverted charge distribution inferring that they undertake different functions in the physiology of the organism. Accordingly, it was shown that the contribution of OmpPst1 in antibiotic uptake is much more important than that of OmpPst2. ..We therefore also went on solving the structures of Omp-Pst1 counterparts in two clinical isolates, viz. Omp-Pst1-99645 and Omp-Pst1-NEA16. The two structures therefore point toward a consensus in the adaptive pathway undertaken by clinical strains. In the pore, mutations permit more pronounced anion selectivity and in a tighter constriction zone. To determine whether these mutations were aimed at reducing antibiotic uptake, we have undertaken the characterization of ?-lactams antibiotics transport kinetics for the three Omp-Pst1 variants. Our results point toward a decreased kon for most antibiotics tested.