RNA-hydrolyzing activity of metallo-β-lactamase IMP-1

Kato, Yoshiki; Takahashi, Masayuki; Seki, Mineaki; Nashimoto, Masayuki; Shimizu‐Ibuka, Akiko

doi:10.1371/journal.pone.0241557

Cited by 6 publications

(4 citation statements)

References 30 publications

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“…First of all, it works by inhibiting the bacterial peptidoglycan cell wall synthesis (16). b-lactamases enzymes hydrolyse the b-lactam antibiotics and may also have different nuclease and hydrolases activities (17)(18)(19)(20)(21)(22)(23)(24). Two mechanistically distincts superfamilies of b-lactamases with two distincts ancestors are described, the nucleophilic serine b-lactamases (class A/C/D); and the zinc ion dependent metallo-b-lactamases (class B) (17,(25)(26)(27).…”

Section: Introductionmentioning

confidence: 99%

Could β-Lactam Antibiotics Block Humoral Immunity?

et al. 2021

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It has been reported that treatment with β-lactam antibiotics induces leukopenia and candidemia, worsens the clinical response to anticancer immunotherapy and decreases immune response to vaccination. β-lactamases can cleave β-lactam antibiotics by blocking their activity. Two distincts superfamilies of β-lactamases are described, the serine β-lactamases and the zinc ion dependent metallo-β-lactamases. In human, 18 metallo-β-lactamases encoding genes (hMBLs) have been identified. While the physiological role of most of them remains unknown, it is well established that the SNM1A, B and C proteins are involved in DNA repair. The SNM1C/Artemis protein is precisely associated in the V(D)J segments rearrangement, that leads to immunoglobulin (Ig) and T-cell receptor variable regions, which have a crucial role in the immune response. Thus in humans, SNM1C/Artemis mutation is associated with severe combined immunodeficiency characterized by hypogammaglobulinemia deficient cellular immunity and opportunistic infections. While catalytic site of hMBLs and especially that of the SNM1 family is highly conserved, in vitro studies showed that some β-lactam antibiotics, and precisely third generation of cephalosporin and ampicillin, inhibit the metallo-β-lactamase proteins SNM1A & B and the SNM1C/Artemis protein complex. By analogy, the question arises as to whether β-lactam antibiotics can block the SNM1C/Artemis protein in humans inducing transient immunodeficiency. We reviewed here the literature data supporting this hypothesis based on in silico, in vitro and in vivo evidences. Understanding the impact of β-lactam antibiotics on the immune cell will offer new therapeutic clues and new clinical approaches in oncology, immunology, and infectious diseases.

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Section: Introductionmentioning

confidence: 99%

Could β-Lactam Antibiotics Block Humoral Immunity?

et al. 2021

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“…Previously reported in the literature, MBL fold proteins can exhibit different promiscuous enzymatic activities such as nuclease and/or ribonuclease activity 14 , 15 . Here, in addition to the detected β-lactam-hydrolysing and ascorbic acid degradation activities of this enzyme, its nuclease and ribonuclease activities were investigated.…”

Section: Resultsmentioning

confidence: 97%

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

Diène

Pinault

Baron

et al. 2021

Sci Rep

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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.

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“…These multiple activities appear as promiscuous activities of these MBL fold enzymes, as suggested in the literature through sequence similarity network analysis [ 25 , 27 ]. Moreover, very recently, RNA-hydrolysis activity of bacterial class B metallo-β-lactamase IMP-1 has been reported experimentally [ 28 ]. The use of antibiotics as a source of nutrients for archaebacteria to degrade the molecules of β-lactam and use them as a source of carbon, as described in the bacteria, is a plausible hypothesis [ 20 , 29 , 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

Dual RNase and β-lactamase Activity of a Single Enzyme Encoded in Archaea

Diène

Pinault

Armstrong

et al. 2020

Life

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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.

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RNA-hydrolyzing activity of metallo-β-lactamase IMP-1

Cited by 6 publications

References 30 publications

Could β-Lactam Antibiotics Block Humoral Immunity?

Could β-Lactam Antibiotics Block Humoral Immunity?

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

Dual RNase and β-lactamase Activity of a Single Enzyme Encoded in Archaea

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