Interplay Between Membrane Permeability and Enzymatic Barrier Leads to Antibiotic-Dependent Resistance in Klebsiella Pneumoniae

Frontiers in Microbiology
Marie-Hélène Nicolas-ChanoineJ M Pagès

Abstract

The interplay between membrane permeability alterations and the enzymatic barrier contributes to Klebsiella pneumoniae multidrug resistance. We assessed the specific effect of the efflux levels of the main efflux pumps (AcrAB and OqxAB), alone and associated with the loss of the main porins (OmpK35 and OMPK36), on the activity of various antibiotics by constructing a set of K. pneumoniae isogenic strains, including strains with plasmid-mediated β-lactamases (DHA-1, CTX-M-15, and OXA-48). The two pumps contributed to intrinsic chloramphenicol resistance and AcrAB to that of nalidixic acid and cefoxitin, whereas they had no impact on the activity of the other 11 antibiotics tested. We confirmed the expulsion of these three antibiotics by the two overproduced pumps and that of tigecycline by overproduced AcrAB, and showed that overproduced AcrAB also expelled ertapenem, piperacillin, ceftolozane, and ceftazidime. The sole loss of porins did not significantly affect the activity of the tested antibiotics, except ertapenem. The effect of efflux increases and porin loss on β-lactam activity was the highest in plasmid-mediated β-lactamase-producing strains. Thus, DHA-1-producing strains became non-susceptible (NS) to (i) ertapenem whe...Continue Reading

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Citations

Dec 4, 2019·Nature Reviews. Microbiology·Julia VergalliJean-Marie Pagès
Feb 15, 2020·Nature Reviews. Microbiology·Kelly L WyresKathryn E Holt
Feb 28, 2020·Clinical Microbiology Reviews·Karen Bush, Patricia A Bradford
Dec 1, 2020·The Journal of Antimicrobial Chemotherapy·Kévin AlexandreFrançois Caron
Sep 11, 2021·Folia Microbiologica·Natália Kehl Moreira, Juliana Caierão
Oct 27, 2021·Advanced Drug Delivery Reviews·Sajid AsgharThierry F Vandamme

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Methods Mentioned

BETA
PCR
gene knockout

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