Paradoxical β-lactamase activity of archaeal encoding enzymes

Diene, S. M.; Pinault, L.; Armstrong, N.; Keshri, V.; Khelaifia, S.; Chabriere, E.; Caetano-Anolles, G.; Rolain, J.-M.; Pontarotti, P.; Raoult, D.

doi:10.1101/667907

bioRxiv · 10.1101/667907

Paradoxical β-lactamase activity of archaeal encoding enzymes

Diene, S. M.·Pinault, L.·Armstrong, N.·Keshri, V.·Khelaifia, S.·Chabriere, E.·Caetano-Anolles, G.·Rolain, J.-M.·Pontarotti, P.·Raoult, D.

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Abstract

{beta}-lactams targeting the bacterial cell wall are not active on archaea. Here, we figure out that annotation of genes as {beta}-lactamase in Archeae on the basis of homologous genes, initially annotated {beta}-lactamases, is a remnant of the identification of the original activities of this group of enzymes, which in fact, have multiple functions including nuclease, ribonuclease, {beta}-lactamase, or glyoxalase; which may specialized over time. We expressed a class B {beta}-lactamase enzyme from Methanosarcina barkeri that digest penicillin G. Moreover, while a weak glyoxalase activity was detected, a significant ribonuclease activity on bacterial and synthetic RNAs was demonstrated. The {beta}-lactamase activity was inhibited by a {beta}-lactamase inhibitor (sulbactam), but its RNAse activity was not. This gene appears to has been transferred to the Flavobacteriaceae group including Elizabethkingia genus in which the expressed gene shows a more specialized activity toward resistance to tienanmicin but no glyoxalase activity. The expressed class C-like {beta}-lactamase gene, also from Methanosarcina sp., shows also hydrolysis activity and was more closely related to DD-peptidase enzymes than known bacterial class C {beta}-lactamases. Our findings highlight the requalification needness of annotated enzymes as {beta}-lactamases and the specification overtime of multipotent enzymes in different ways in Archaea and bacteria.

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Diene, S. M., Pinault, L., Armstrong, N., Keshri, V., Khelaifia, S., Chabriere, E., Caetano-Anolles, G., Rolain, J.-M., Pontarotti, P., Raoult, D.. 2019-06-12. Paradoxical β-lactamase activity of archaeal encoding enzymes. https://doi.org/10.1101/667907

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