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Role of enzymatic a...
Role of enzymatic activity in the biological cost associated with the production of ampC b-lactamases in pseudomonas aeruginosa
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- Barceló, Isabel M. (författare)
- Research Unit, University Hospital Son Espases, Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain; Microbiology Department, University Hospital Son Espases, Palma, Spain; Centro de Investigación Biomédica en Red, Enfermedades Infecciosas, Madrid, Spain
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- Jordana-Lluch, Elena (författare)
- Research Unit, University Hospital Son Espases, Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain; Microbiology Department, University Hospital Son Espases, Palma, Spain
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- Escobar-Salom, María (författare)
- Research Unit, University Hospital Son Espases, Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain; Microbiology Department, University Hospital Son Espases, Palma, Spain; Centro de Investigación Biomédica en Red, Enfermedades Infecciosas, Madrid, Spain
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- Torrens, Gabriel (författare)
- Umeå universitet,Umeå Centre for Microbial Research (UCMR),Molekylär Infektionsmedicin, Sverige (MIMS),Institutionen för molekylärbiologi (Medicinska fakulteten),Research Unit, University Hospital Son Espases, Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain; Microbiology Department, University Hospital Son Espases, Palma, Spain; Centro de Investigación Biomédica en Red, Enfermedades Infecciosas, Madrid, Spain
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- Fraile-Ribot, Pablo A. (författare)
- Research Unit, University Hospital Son Espases, Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain; Microbiology Department, University Hospital Son Espases, Palma, Spain; Centro de Investigación Biomédica en Red, Enfermedades Infecciosas, Madrid, Spain
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- Cabot, Gabriel (författare)
- Research Unit, University Hospital Son Espases, Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain; Microbiology Department, University Hospital Son Espases, Palma, Spain; Centro de Investigación Biomédica en Red, Enfermedades Infecciosas, Madrid, Spain
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- Mulet, Xavier (författare)
- Research Unit, University Hospital Son Espases, Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain; Microbiology Department, University Hospital Son Espases, Palma, Spain; Centro de Investigación Biomédica en Red, Enfermedades Infecciosas, Madrid, Spain
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- Zamorano, Laura (författare)
- Research Unit, University Hospital Son Espases, Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain; Microbiology Department, University Hospital Son Espases, Palma, Spain; Centro de Investigación Biomédica en Red, Enfermedades Infecciosas, Madrid, Spain
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- Juan, Carlos (författare)
- Research Unit, University Hospital Son Espases, Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain; Microbiology Department, University Hospital Son Espases, Palma, Spain; Centro de Investigación Biomédica en Red, Enfermedades Infecciosas, Madrid, Spain
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- Oliver, Antonio (författare)
- Research Unit, University Hospital Son Espases, Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain; Microbiology Department, University Hospital Son Espases, Palma, Spain; Centro de Investigación Biomédica en Red, Enfermedades Infecciosas, Madrid, Spain
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(creator_code:org_t)
- American Society for Microbiology, 2022
- 2022
- Engelska.
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Ingår i: Microbiology Spectrum. - : American Society for Microbiology. - 2165-0497. ; 10:5
- Relaterad länk:
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- In the current scenario of growing antibiotic resistance, understanding the interplay between resistance mechanisms and biological costs is crucial for designing therapeutic strategies. In this regard, intrinsic AmpC β-lactamase hyperproduction is probably themost important resistancemechanismof Pseudomonas aeruginosa, proven to entail important biological burdens that attenuate virulence mostly under peptidoglycan recycling alterations. P. aeruginosa can acquire resistance to new β-lactam-β-lactamase inhibitor combinations (ceftazidime-avibactam and ceftolozane-tazobactam) through mutations affecting ampC and its regulatory genes, but the impact of these mutations on the associated biological cost and the role that β-lactamase activity plays per se in contributing to the above-mentioned virulence attenuation are unknown. The same questions remain unsolved for plasmid-encoded AmpC-type β-lactamases such as FOX enzymes, some of which also provide resistance to new β-lactam-β-lactamase inhibitor combinations. Here, we assessed from different perspectives the effects of changes in the active center and, thus, in the hydrolytic spectrum resistance to inhibitors of AmpC-type β-lactamases on the fitness and virulence of P. aeruginosa, using site-directed mutagenesis; the previously described AmpC variants T96I, G183D, and ΔG229-E247; and, finally, blaFOX-4 versus blaFOX-8. Our results indicate the essential role of AmpC activity per se in causing the reported full virulence attenuation (in terms of growth, motility, cytotoxicity, and Galleria mellonella larvae killing), although the biological cost of the above-mentioned AmpC-type variants was similar to that of the wild-type enzymes. This suggests that there is not an important biological burden that may limit the selection/spread of these variants, which could progressively compromise the future effectiveness of the above-mentioned drug combinations.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
Nyckelord
- AmpC
- biological cost
- blaFOX β-lactamases
- ceftazidimeavibactam
- ceftolozane-tazobactam
- fitness
- Galleria mellonella
- peptidoglycan recycling
- Pseudomonas aeruginosa
- virulence
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Barceló, Isabel ...
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Jordana-Lluch, E ...
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Escobar-Salom, M ...
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Torrens, Gabriel
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Fraile-Ribot, Pa ...
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Cabot, Gabriel
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visa fler...
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Mulet, Xavier
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Zamorano, Laura
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Juan, Carlos
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Oliver, Antonio
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Mikrobiologi ino ...
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Microbiology Spe ...
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Umeå universitet