Human metallo-β-lactamase enzymes degrade penicillin

Sci Rep. 2019 Aug 21;9(1):12173. doi: 10.1038/s41598-019-48723-y.

Seydina M Diene ¹ ², Lucile Pinault ³, Vivek Keshri ¹ ², Nicholas Armstrong ³, Saber Khelaifia ¹ ², Eric Chabrière ¹, Gustavo Caetano-Anolles ⁴, Philippe Colson ¹ ³ ², Bernard La Scola ¹ ³ ², Jean-Marc Rolain ¹ ³ ², Pierre Pontarotti ¹ ² ⁴ ⁵, Didier Raoult ⁶ ⁷ ⁸

Affiliations

1 Aix Marseille Université, MEPHI, IHU-Méditerranée Infection, Marseille, France.
2 IHU-Méditerranée Infection, Marseille, France.
3 Assistance Publique-Hôpitaux de Marseille (AP-HM), IHU-Méditerranée Infection, Marseille, France.
4 Evolutionary Bioinformatics Laboratory, Department of Crop Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
5 CNRS, Marseille, France.
6 Aix Marseille Université, MEPHI, IHU-Méditerranée Infection, Marseille, France. didier.raoult@gmail.com.
7 Assistance Publique-Hôpitaux de Marseille (AP-HM), IHU-Méditerranée Infection, Marseille, France. didier.raoult@gmail.com.
8 IHU-Méditerranée Infection, Marseille, France. didier.raoult@gmail.com.

PMID: 31434986 DOI: 10.1038/s41598-019-48723-y

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.

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