| dc.creator | Colque, Claudia A. | |
| dc.creator | Albarracín Orio, Andrea Georgina | |
| dc.creator | Tomatis, Pablo Emiliano | |
| dc.creator | Dotta, Gina | |
| dc.creator | Moreno, Diego M. | |
| dc.creator | Hedemann, Laura Gabriela | |
| dc.creator | Hickman, Rachel | |
| dc.creator | Madsen Sommer, Lea Mette | |
| dc.creator | Feliziani, Sofía | |
| dc.creator | Moyano, Alejandro José | |
| dc.creator | Bonomo, Robert | |
| dc.creator | Johansen, Helle Krogh | |
| dc.creator | Molin, Søren | |
| dc.creator | Vila, Alejandro | |
| dc.creator | Smania, Andrea M. | |
| dc.date | 2022-09-08 | |
| dc.date.accessioned | 2023-04-10T17:50:29Z | |
| dc.date.available | 2023-04-10T17:50:29Z | |
| dc.identifier | http://pa.bibdigital.ucc.edu.ar/3687/1/A_Colque_Albarrac%C3%ADnOrio_Tomatis_Dotta_Moreno_Hedemann_Hickman_Sommer_Feliziani_Moyano_Bonomo_Johansen_Molin_Vila_Smania.pdf | |
| dc.identifier.uri | https://hdl.handle.net/20.500.12032/86139 | |
| dc.description | Traditional studies on the evolution of antibiotic resistance development use approaches that can range from laboratory-based experimental studies, to epidemiological
surveillance, to sequencing of clinical isolates. However, evolutionary trajectories also depend on the environment in which selection takes place, compelling the need to more
deeply investigate the impact of environmental complexities and their dynamics over time.
Herein, we explored the within-patient adaptive long-term evolution of a Pseudomonas aeruginosa hypermutator lineage in the airways of a cystic fibrosis (CF) patient by performing a chronological tracking of mutations that occurred in different subpopulations; our results
demonstrated parallel evolution events in the chromosomally encoded class C b-lactamase (blaPDC). These multiple mutations within blaPDC shaped diverse coexisting alleles, whose frequency dynamics responded to the changing antibiotic selective pressures for more than 26 years of chronic infection. Importantly, the combination of the cumulative mutations in blaPDC provided structural and functional protein changes that resulted in a continuous
enhancement of its catalytic efficiency and high level of cephalosporin resistance. This evolution was linked to the persistent treatment with ceftazidime, which we demonstrated
selected for variants with robust catalytic activity against this expanded-spectrum cephalosporin. A “gain of function” of collateral resistance toward ceftolozane, a more recently
introduced cephalosporin that was not prescribed to this patient, was also observed, and the biochemical basis of this cross-resistance phenomenon was elucidated. This work
unveils the evolutionary trajectories paved by bacteria toward a multidrug-resistant phenotype, driven by decades of antibiotic treatment in the natural CF environmental setting. | |
| dc.description | Fil: Colque, Claudia A. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina | |
| dc.description | Fil: Albarracín Orio, Andrea Georgina. Universidad Católica de Córdoba. Facultad de Ciencias Agropecuarias; Argentina | |
| dc.description | Fil: Tomatis, Pablo Emiliano. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina | |
| dc.description | Fil: Dotta, Gina. Universidad Nacional de Rosario. Instituto de Biología Molecular; Argentina | |
| dc.description | Fil: Moreno, Diego M. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina | |
| dc.description | Fil: Hedemann, Laura Gabriela. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina | |
| dc.description | Fil: Hickman, Rachel. Technical University of Denmark; Dinamarca | |
| dc.description | Fil: Madsen Sommer, Lea Mette. Technical University of Denmark; Dinamarca | |
| dc.description | Fil: Feliziani, Sofía. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina | |
| dc.description | Fil: Moyano, Alejandro José. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina | |
| dc.description | Fil: Bonomo, Robert. Case Western Reserve University; Estados Unidos | |
| dc.description | Fil: Johansen, Helle Krogh. University of Copenhagen; Dinamarca | |
| dc.description | Fil: Molin, Søren. Technical University of Denmark; Dinamarca | |
| dc.description | Fil: Vila, Alejandro. niversidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina | |
| dc.description | Fil: Smania, Andrea M. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina | |
| dc.format | application/pdf | |
| dc.language | spa | |
| dc.relation | http://pa.bibdigital.ucc.edu.ar/3687/ | |
| dc.relation | info:eu-repo/semantics/altIdentifier/doi/0.1128/mbio.01663-22 | |
| dc.rights | info:eu-repo/semantics/openAccess | |
| dc.rights | https://creativecommons.org/licenses/by/4.0/deed.es | |
| dc.source | Colque, Claudia A. ORCID: https://orcid.org/0000-0002-9027-4747 <https://orcid.org/0000-0002-9027-4747>, Albarracín Orio, Andrea Georgina ORCID: https://orcid.org/0000-0002-4722-1439 <https://orcid.org/0000-0002-4722-1439>, Tomatis, Pablo Emiliano ORCID: https://orcid.org/0000-0002-1126-8200 <https://orcid.org/0000-0002-1126-8200>, Dotta, Gina ORCID: https://orcid.org/0000-0003-1023-1606 <https://orcid.org/0000-0003-1023-1606>, Moreno, Diego M. ORCID: https://orcid.org/0000-0001-5493-8537 <https://orcid.org/0000-0001-5493-8537>, Hedemann, Laura Gabriela ORCID: https://orcid.org/0000-0002-6667-6500 <https://orcid.org/0000-0002-6667-6500>, Hickman, Rachel ORCID: https://orcid.org/0000-0002-0290-1836 <https://orcid.org/0000-0002-0290-1836>, Madsen Sommer, Lea Mette ORCID: https://orcid.org/0000-0002-1622-6691 <https://orcid.org/0000-0002-1622-6691>, Feliziani, Sofía, Moyano, Alejandro José ORCID: https://orcid.org/0000-0002-4976-7611 <https://orcid.org/0000-0002-4976-7611>, Bonomo, Robert ORCID: https://orcid.org/0000-0002-3299-894X <https://orcid.org/0000-0002-3299-894X>, Johansen, Helle Krogh ORCID: https://orcid.org/0000-0003-0268-3717 <https://orcid.org/0000-0003-0268-3717>, Molin, Søren ORCID: https://orcid.org/0000-0002-7973-2639 <https://orcid.org/0000-0002-7973-2639>, Vila, Alejandro ORCID: https://orcid.org/0000-0002-7978-3233 <https://orcid.org/0000-0002-7978-3233> and Smania, Andrea M. (2022) Longitudinal Evolution of the Pseudomonas-Derived Cephalosporinase (PDC) Structure and Activity in a Cystic Fibrosis Patient Treated with β-Lactams. mBio, 13 (5). | |
| dc.subject | R Medicina (General) | |
| dc.title | Longitudinal Evolution of the Pseudomonas-Derived Cephalosporinase (PDC) Structure and Activity in a Cystic Fibrosis Patient Treated with β-Lactams | |
| dc.type | info:eu-repo/semantics/article | |
| dc.type | info:ar-repo/semantics/artículo | |
| dc.type | info:eu-repo/semantics/acceptedVersion | |
