β-Lactam antibiotic-degrading enzymes from non-pathogenic marine organisms: a potential threat to human health

Miraula, Manfredi, Whitaker, Jacob J, Schenk, Gerhard and Mitic, Natasa (2015) β-Lactam antibiotic-degrading enzymes from non-pathogenic marine organisms: a potential threat to human health. Journal of Biological Inorganic Chemistry, 20 4: 639-651. doi:10.1007/s00775-015-1250-x


Author Miraula, Manfredi
Whitaker, Jacob J
Schenk, Gerhard
Mitic, Natasa
Title β-Lactam antibiotic-degrading enzymes from non-pathogenic marine organisms: a potential threat to human health
Journal name Journal of Biological Inorganic Chemistry   Check publisher's open access policy
ISSN 1432-1327
0949-8257
Publication date 2015-03-14
Year available 2015
Sub-type Article (original research)
DOI 10.1007/s00775-015-1250-x
Open Access Status
Volume 20
Issue 4
Start page 639
End page 651
Total pages 13
Place of publication Heidelberg, Germany
Publisher Springer
Collection year 2016
Formatted abstract
Metallo-β-lactamases (MBLs) are a family of Zn(II)-dependent enzymes that inactivate most of the commonly used β-lactam antibiotics. They have emerged as a major threat to global healthcare. Recently, we identified two novel MBL-like proteins, Maynooth IMipenemase-1 (MIM-1) and Maynooth IMipenemase-2 (MIM-2), in the marine organisms Novosphingobium pentaromativorans and Simiduia agarivorans, respectively. Here, we demonstrate that MIM-1 and MIM-2 have catalytic activities comparable to those of known MBLs, but from the pH dependence of their catalytic parameters it is evident that both enzymes differ with respect to their mechanisms, with MIM-1 preferring alkaline and MIM-2 acidic conditions. Both enzymes require Zn(II) but activity can also be reconstituted with other metal ions including Co(II), Mn(II), Cu(II) and Ca(II). Importantly, the substrate preference of MIM-1 and MIM-2 appears to be influenced by their metal ion composition. Since neither N. pentaromativorans nor S. agarivorans are human pathogens, the precise biological role(s) of MIM-1 and MIM-2 remains to be established. However, due to the similarity of at least some of their in vitro functional properties to those of known MBLs, MIM-1 and MIM-2 may provide essential structural insight that may guide the design of as of yet elusive clinically useful MBL inhibitors.
Keyword Antibiotic resistance
β-Lactam antibiotics
Metallo-β-lactamase
Metallohydrolase
Catalysis
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Chemistry and Molecular Biosciences
 
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