A metallo-β-lactamase enzyme for internal detoxification of the antibiotic thienamycin

Abstract Thienamycin, the first representative of carbapenem antibiotics was discovered in the mid-1970s from soil microorganism, Streptomyces cattleya, during the race to discover inhibitors of bacterial peptidoglycan synthesis. Chemically modified into imipenem (N-formimidoyl thienamycin), now one...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Seydina M. Diene, Lucile Pinault, Sophie Alexandra Baron, Saïd Azza, Nicholas Armstrong, Linda Hadjadj, Eric Chabrière, Jean-Marc Rolain, Pierre Pontarotti, Didier Raoult
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/175861a67ee74230a4d1d98cf4c42f8d
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:175861a67ee74230a4d1d98cf4c42f8d
record_format	dspace
spelling	oai:doaj.org-article:175861a67ee74230a4d1d98cf4c42f8d2021-12-02T16:50:27ZA metallo-β-lactamase enzyme for internal detoxification of the antibiotic thienamycin10.1038/s41598-021-89600-x2045-2322https://doaj.org/article/175861a67ee74230a4d1d98cf4c42f8d2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89600-xhttps://doaj.org/toc/2045-2322Abstract Thienamycin, the first representative of carbapenem antibiotics was discovered in the mid-1970s from soil microorganism, Streptomyces cattleya, during the race to discover inhibitors of bacterial peptidoglycan synthesis. Chemically modified into imipenem (N-formimidoyl thienamycin), now one of the most clinically important antibiotics, thienamycin is encoded by a thienamycin gene cluster composed of 22 genes (thnA to thnV) from S. cattleya NRRL 8057 genome. Interestingly, the role of all thn-genes has been experimentally demonstrated in the thienamycin biosynthesis, except thnS, despite its annotation as putative β-lactamase. Here, we expressed thnS gene and investigated its activities against various substrates. Our analyses revealed that ThnS belonged to the superfamily of metallo-β-lactamase fold proteins. Compared to known β-lactamases such as OXA-48 and NDM-1, ThnS exhibited a lower affinity and less efficiency toward penicillin G and cefotaxime, while imipenem is more actively hydrolysed. Moreover, like most MBL fold enzymes, additional enzymatic activities of ThnS were detected such as hydrolysis of ascorbic acid, single strand DNA, and ribosomal RNA. ThnS appears as a MBL enzyme with multiple activities including a specialised β-lactamase activity toward imipenem. Thus, like toxin/antitoxin systems, the role of thnS gene within the thienamycin gene cluster appears as an antidote against the produced thienamycin.Seydina M. DieneLucile PinaultSophie Alexandra BaronSaïd AzzaNicholas ArmstrongLinda HadjadjEric ChabrièreJean-Marc RolainPierre PontarottiDidier RaoultNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Seydina M. Diene Lucile Pinault Sophie Alexandra Baron Saïd Azza Nicholas Armstrong Linda Hadjadj Eric Chabrière Jean-Marc Rolain Pierre Pontarotti Didier Raoult A metallo-β-lactamase enzyme for internal detoxification of the antibiotic thienamycin
description	Abstract Thienamycin, the first representative of carbapenem antibiotics was discovered in the mid-1970s from soil microorganism, Streptomyces cattleya, during the race to discover inhibitors of bacterial peptidoglycan synthesis. Chemically modified into imipenem (N-formimidoyl thienamycin), now one of the most clinically important antibiotics, thienamycin is encoded by a thienamycin gene cluster composed of 22 genes (thnA to thnV) from S. cattleya NRRL 8057 genome. Interestingly, the role of all thn-genes has been experimentally demonstrated in the thienamycin biosynthesis, except thnS, despite its annotation as putative β-lactamase. Here, we expressed thnS gene and investigated its activities against various substrates. Our analyses revealed that ThnS belonged to the superfamily of metallo-β-lactamase fold proteins. Compared to known β-lactamases such as OXA-48 and NDM-1, ThnS exhibited a lower affinity and less efficiency toward penicillin G and cefotaxime, while imipenem is more actively hydrolysed. Moreover, like most MBL fold enzymes, additional enzymatic activities of ThnS were detected such as hydrolysis of ascorbic acid, single strand DNA, and ribosomal RNA. ThnS appears as a MBL enzyme with multiple activities including a specialised β-lactamase activity toward imipenem. Thus, like toxin/antitoxin systems, the role of thnS gene within the thienamycin gene cluster appears as an antidote against the produced thienamycin.
format	article
author	Seydina M. Diene Lucile Pinault Sophie Alexandra Baron Saïd Azza Nicholas Armstrong Linda Hadjadj Eric Chabrière Jean-Marc Rolain Pierre Pontarotti Didier Raoult
author_facet	Seydina M. Diene Lucile Pinault Sophie Alexandra Baron Saïd Azza Nicholas Armstrong Linda Hadjadj Eric Chabrière Jean-Marc Rolain Pierre Pontarotti Didier Raoult
author_sort	Seydina M. Diene
title	A metallo-β-lactamase enzyme for internal detoxification of the antibiotic thienamycin
title_short	A metallo-β-lactamase enzyme for internal detoxification of the antibiotic thienamycin
title_full	A metallo-β-lactamase enzyme for internal detoxification of the antibiotic thienamycin
title_fullStr	A metallo-β-lactamase enzyme for internal detoxification of the antibiotic thienamycin
title_full_unstemmed	A metallo-β-lactamase enzyme for internal detoxification of the antibiotic thienamycin
title_sort	metallo-β-lactamase enzyme for internal detoxification of the antibiotic thienamycin
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/175861a67ee74230a4d1d98cf4c42f8d
work_keys_str_mv	AT seydinamdiene ametalloblactamaseenzymeforinternaldetoxificationoftheantibioticthienamycin AT lucilepinault ametalloblactamaseenzymeforinternaldetoxificationoftheantibioticthienamycin AT sophiealexandrabaron ametalloblactamaseenzymeforinternaldetoxificationoftheantibioticthienamycin AT saidazza ametalloblactamaseenzymeforinternaldetoxificationoftheantibioticthienamycin AT nicholasarmstrong ametalloblactamaseenzymeforinternaldetoxificationoftheantibioticthienamycin AT lindahadjadj ametalloblactamaseenzymeforinternaldetoxificationoftheantibioticthienamycin AT ericchabriere ametalloblactamaseenzymeforinternaldetoxificationoftheantibioticthienamycin AT jeanmarcrolain ametalloblactamaseenzymeforinternaldetoxificationoftheantibioticthienamycin AT pierrepontarotti ametalloblactamaseenzymeforinternaldetoxificationoftheantibioticthienamycin AT didierraoult ametalloblactamaseenzymeforinternaldetoxificationoftheantibioticthienamycin AT seydinamdiene metalloblactamaseenzymeforinternaldetoxificationoftheantibioticthienamycin AT lucilepinault metalloblactamaseenzymeforinternaldetoxificationoftheantibioticthienamycin AT sophiealexandrabaron metalloblactamaseenzymeforinternaldetoxificationoftheantibioticthienamycin AT saidazza metalloblactamaseenzymeforinternaldetoxificationoftheantibioticthienamycin AT nicholasarmstrong metalloblactamaseenzymeforinternaldetoxificationoftheantibioticthienamycin AT lindahadjadj metalloblactamaseenzymeforinternaldetoxificationoftheantibioticthienamycin AT ericchabriere metalloblactamaseenzymeforinternaldetoxificationoftheantibioticthienamycin AT jeanmarcrolain metalloblactamaseenzymeforinternaldetoxificationoftheantibioticthienamycin AT pierrepontarotti metalloblactamaseenzymeforinternaldetoxificationoftheantibioticthienamycin AT didierraoult metalloblactamaseenzymeforinternaldetoxificationoftheantibioticthienamycin
_version_	1718383021464223744

A metallo-β-lactamase enzyme for internal detoxification of the antibiotic thienamycin

Ejemplares similares