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In vitro evaluation of metal chelators as potential metallo‐ β ‐lactamase inhibitors
Author(s) -
Azumah R.,
Dutta J.,
Somboro A.M.,
Ramtahal M.,
Chonco L.,
Parboosing R.,
Bester L.A.,
Kruger H.G.,
Naicker T.,
Essack S.Y.,
Govender T.
Publication year - 2016
Publication title -
journal of applied microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.889
H-Index - 156
eISSN - 1365-2672
pISSN - 1364-5072
DOI - 10.1111/jam.13085
Subject(s) - meropenem , broth microdilution , chemistry , minimum inhibitory concentration , chelation , enterobacteriaceae , microbiology and biotechnology , biochemistry , antibiotics , nuclear chemistry , biology , escherichia coli , organic chemistry , antibiotic resistance , gene
Aims This study aimed at investigating the use of metal chelators as potential metallo‐β‐lactamase inhibitors ( MBL ). Methods and Results The minimum inhibitory concentration ( MIC ) of meropenem was ascertained alone and in combination with various concentrations of macrocyclic (1,4,7‐ triazacyclononane‐1‐glutaric acid‐4,7‐diacetic acid = NODAGA ) peptide derivatives and acyclic (N ,N,N′,N′‐ Tetrakis(2‐pyridylmethyl)ethylenediamine = TPEN and di‐(2‐picolyl)amine = DPA ) metal chelators using the broth microdilution method. MIC s of meropenem against carbapenem‐resistant enterobacteriaceae ( CRE ) producing MBL s were decreased to concentrations as low as 0·06 mg l −1 in the presence of some metal chelators. TPEN at 4 and 8 mg l −1 showed the best activity by decreasing meropenem MIC s to 0·5 and 0·06 mg l −1 , respectively, for some New Delhi Metallo‐beta‐lactamase ( NDM ) and Verona integron‐encoded metallo‐β‐lactamase ( VIM ) ‐producing enterobacteriaceae. DPA at 8 and 16 mg l −1 was also able to decrease meropenem MIC s to 1 and 0·125 mg l −1 , respectively, for these CRE s. NODAGA peptide derivatives showed the least inhibition as 32 mg l −1 was required for meropenem MIC s to be decreased to 0·06 mg l −1 against an NDM ‐1 producing isolate. Conclusion The various metal chelators, TPEN , DPA and NODAGA peptide derivatives were able to inhibit the MBL s in decreasing order of activity, rendering CRE s susceptible to meropenem. Significance and Impact of the Study In the absence of new antibiotics, this study evaluated metal chelators as potential MBL inhibitors.