Human metallo-β-lactamase enzymes degrade penicillin

Abstract Nonribosomal peptides are assemblages, including antibiotics, of canonical amino acids and other molecules. β-lactam antibiotics act on bacterial cell walls and can be cleaved by β-lactamases. β-lactamase activity in humans has been neglected, even though eighteen enzymes have already been...

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Autores principales: Seydina M. Diene, Lucile Pinault, Vivek Keshri, Nicholas Armstrong, Saber Khelaifia, Eric Chabrière, Gustavo Caetano-Anolles, Philippe Colson, Bernard La Scola, Jean-Marc Rolain, Pierre Pontarotti, Didier Raoult
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Lenguaje:EN
Publicado: Nature Portfolio 2019
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Acceso en línea:https://doaj.org/article/85f64b16e26b4baca5d5358296d9896c
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spelling oai:doaj.org-article:85f64b16e26b4baca5d5358296d9896c2021-12-02T16:08:05ZHuman metallo-β-lactamase enzymes degrade penicillin10.1038/s41598-019-48723-y2045-2322https://doaj.org/article/85f64b16e26b4baca5d5358296d9896c2019-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-48723-yhttps://doaj.org/toc/2045-2322Abstract Nonribosomal peptides are assemblages, including antibiotics, of canonical amino acids and other molecules. β-lactam antibiotics act on bacterial cell walls and can be cleaved by β-lactamases. β-lactamase activity in humans has been neglected, even though eighteen enzymes have already been annotated such in human genome. Their hydrolysis activities on antibiotics have not been previously investigated. Here, we report that human cells were able to digest penicillin and this activity was inhibited by β-lactamase inhibitor, i.e. sulbactam. Penicillin degradation in human cells was microbiologically demonstrated on Pneumococcus. We expressed a MBLAC2 human β-lactamase, known as an exosome biogenesis enzyme. It cleaved penicillin and was inhibited by sulbactam. Finally, β-lactamases are widely distributed, archaic, and have wide spectrum, including digesting anticancer and β-lactams, that can be then used as nutriments. The evidence of the other MBLAC2 role as a bona fide β-lactamase allows for reassessment of β-lactams and β-lactamases role in humans.Seydina M. DieneLucile PinaultVivek KeshriNicholas ArmstrongSaber KhelaifiaEric ChabrièreGustavo Caetano-AnollesPhilippe ColsonBernard La ScolaJean-Marc RolainPierre PontarottiDidier RaoultNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-7 (2019)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Seydina M. Diene
Lucile Pinault
Vivek Keshri
Nicholas Armstrong
Saber Khelaifia
Eric Chabrière
Gustavo Caetano-Anolles
Philippe Colson
Bernard La Scola
Jean-Marc Rolain
Pierre Pontarotti
Didier Raoult
Human metallo-β-lactamase enzymes degrade penicillin
description Abstract Nonribosomal peptides are assemblages, including antibiotics, of canonical amino acids and other molecules. β-lactam antibiotics act on bacterial cell walls and can be cleaved by β-lactamases. β-lactamase activity in humans has been neglected, even though eighteen enzymes have already been annotated such in human genome. Their hydrolysis activities on antibiotics have not been previously investigated. Here, we report that human cells were able to digest penicillin and this activity was inhibited by β-lactamase inhibitor, i.e. sulbactam. Penicillin degradation in human cells was microbiologically demonstrated on Pneumococcus. We expressed a MBLAC2 human β-lactamase, known as an exosome biogenesis enzyme. It cleaved penicillin and was inhibited by sulbactam. Finally, β-lactamases are widely distributed, archaic, and have wide spectrum, including digesting anticancer and β-lactams, that can be then used as nutriments. The evidence of the other MBLAC2 role as a bona fide β-lactamase allows for reassessment of β-lactams and β-lactamases role in humans.
format article
author Seydina M. Diene
Lucile Pinault
Vivek Keshri
Nicholas Armstrong
Saber Khelaifia
Eric Chabrière
Gustavo Caetano-Anolles
Philippe Colson
Bernard La Scola
Jean-Marc Rolain
Pierre Pontarotti
Didier Raoult
author_facet Seydina M. Diene
Lucile Pinault
Vivek Keshri
Nicholas Armstrong
Saber Khelaifia
Eric Chabrière
Gustavo Caetano-Anolles
Philippe Colson
Bernard La Scola
Jean-Marc Rolain
Pierre Pontarotti
Didier Raoult
author_sort Seydina M. Diene
title Human metallo-β-lactamase enzymes degrade penicillin
title_short Human metallo-β-lactamase enzymes degrade penicillin
title_full Human metallo-β-lactamase enzymes degrade penicillin
title_fullStr Human metallo-β-lactamase enzymes degrade penicillin
title_full_unstemmed Human metallo-β-lactamase enzymes degrade penicillin
title_sort human metallo-β-lactamase enzymes degrade penicillin
publisher Nature Portfolio
publishDate 2019
url https://doaj.org/article/85f64b16e26b4baca5d5358296d9896c
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