TY - JOUR
T1 - Dual RNase and β-lactamase Activity of a Single Enzyme Encoded in Archaea
AU - Diene, Seydina M.
AU - Pinault, Lucile
AU - Armstrong, Nicholas
AU - Azza, Said
AU - Keshri, Vivek
AU - Khelaifia, Saber
AU - Chabrière, Eric
AU - Caetano-Anolles, Gustavo
AU - Rolain, Jean Marc
AU - Pontarotti, Pierre
AU - Raoult, Didier
N1 - Funding Information:
Funding: This work was supported by the French Government under the “Investments for the Future” program managed by the National Agency for Research (ANR), Méditerranée-Infection and was also supported by Région Provence Alpes Côte d’Azur and European funding FEDER PRIMMI (Fonds Européen de Développement Régional—Plateformes de Recherche et d’Innovation Mutualisées Méditerranée Infection).
Funding Information:
Acknowledgments: Financial support from the IHU Mediterranee Infection, Marseille France, and American Journal Experts (AJE) for English corrections of the manuscript are gratefully acknowledged.
PY - 2020/11/14
Y1 - 2020/11/14
N2 - β-lactam antibiotics have a well-known activity which disturbs the bacterial cell wall biosynthesis and may be cleaved by β-lactamases. However, these drugs are not active on archaea microorganisms, which are naturally resistant because of the lack of β-lactam target in their cell wall. Here, we describe that annotation of genes as β-lactamases in Archaea on the basis of homologous genes is a remnant of identification of the original activities of this group of enzymes, which in fact have multiple functions, including nuclease, ribonuclease, β-lactamase, or glyoxalase, which may specialized over time. We expressed class B β-lactamase enzyme from Methanosarcina barkeri that digest penicillin G. Moreover, while weak glyoxalase activity was detected, a significant ribonuclease activity on bacterial and synthetic RNAs was demonstrated. The β-lactamase activity was inhibited by β-lactamase inhibitor (sulbactam), but its RNAse activity was not. This gene appears to have been transferred to the Flavobacteriaceae group especially the Elizabethkingia genus, in which the expressed gene shows a more specialized activity on thienamycin, but no glyoxalase activity. The expressed class C-like β-lactamase gene, from Methanosarcina sp., also shows hydrolysis activity on nitrocefin and is more closely related to DD-peptidase enzymes. Our findings highlight the need to redefine the nomenclature of β-lactamase enzymes and the specification of multipotent enzymes in different ways in Archaea and bacteria over time.
AB - β-lactam antibiotics have a well-known activity which disturbs the bacterial cell wall biosynthesis and may be cleaved by β-lactamases. However, these drugs are not active on archaea microorganisms, which are naturally resistant because of the lack of β-lactam target in their cell wall. Here, we describe that annotation of genes as β-lactamases in Archaea on the basis of homologous genes is a remnant of identification of the original activities of this group of enzymes, which in fact have multiple functions, including nuclease, ribonuclease, β-lactamase, or glyoxalase, which may specialized over time. We expressed class B β-lactamase enzyme from Methanosarcina barkeri that digest penicillin G. Moreover, while weak glyoxalase activity was detected, a significant ribonuclease activity on bacterial and synthetic RNAs was demonstrated. The β-lactamase activity was inhibited by β-lactamase inhibitor (sulbactam), but its RNAse activity was not. This gene appears to have been transferred to the Flavobacteriaceae group especially the Elizabethkingia genus, in which the expressed gene shows a more specialized activity on thienamycin, but no glyoxalase activity. The expressed class C-like β-lactamase gene, from Methanosarcina sp., also shows hydrolysis activity on nitrocefin and is more closely related to DD-peptidase enzymes. Our findings highlight the need to redefine the nomenclature of β-lactamase enzymes and the specification of multipotent enzymes in different ways in Archaea and bacteria over time.
KW - Archaea
KW - Common ancestor sequence
KW - Core genes
KW - Glyoxalases
KW - Metallo-β-lactamases
KW - Ribonucleases
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U2 - 10.3390/life10110280
DO - 10.3390/life10110280
M3 - Article
C2 - 33202677
SN - 2075-1729
VL - 10
SP - 1
EP - 12
JO - Life
JF - Life
IS - 11
M1 - 280
ER -