title: In vitro evaluation of metal chelators as potential metallo- β -lactamase inhibitors.
abstract: OBJECTIVE
  This study aimed at investigating the use of metal chelators as potential metallo-β-lactamase inhibitors (MBL).
  
  
  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. MICs of meropenem against carbapenem-resistant enterobacteriaceae (CRE) producing MBLs 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 MICs 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 MICs to 1 and 0·125 mg l(-1) , respectively, for these CREs. NODAGA peptide derivatives showed the least inhibition as 32 mg l(-1) was required for meropenem MICs to be decreased to 0·06 mg l(-1) against an NDM-1 producing isolate.
  
  
  CONCLUSIONS
  The various metal chelators, TPEN, DPA and NODAGA peptide derivatives were able to inhibit the MBLs in decreasing order of activity, rendering CREs susceptible to meropenem.
  
  
  CONCLUSIONS
  In the absence of new antibiotics, this study evaluated metal chelators as potential MBL inhibitors.
authors: Catalysis and Peptide Research Unit, School of Health Sciences, University of Kwa-Zulu Natal, Durban, South Africa.|Antimicrobial Research Unit, School of Health Sciences, University of Kwa-Zulu Natal, Durban, South Africa.
authors: R
authors: R
authors: Azumah
authors: Catalysis and Peptide Research Unit, School of Health Sciences, University of Kwa-Zulu Natal, Durban, South Africa.
authors: J
authors: J
authors: Dutta
authors: Catalysis and Peptide Research Unit, School of Health Sciences, University of Kwa-Zulu Natal, Durban, South Africa.|Antimicrobial Research Unit, School of Health Sciences, University of Kwa-Zulu Natal, Durban, South Africa.
authors: A M
authors: AM
authors: Somboro
authors: Catalysis and Peptide Research Unit, School of Health Sciences, University of Kwa-Zulu Natal, Durban, South Africa.|Antimicrobial Research Unit, School of Health Sciences, University of Kwa-Zulu Natal, Durban, South Africa.
authors: M
authors: M
authors: Ramtahal
authors: Department of Virology, National Health Laboratory Service, University of KwaZulu-Natal, Durban, South Africa.
authors: L
authors: L
authors: Chonco
authors: Department of Virology, National Health Laboratory Service, University of KwaZulu-Natal, Durban, South Africa.
authors: R
authors: R
authors: Parboosing
authors: Biomedical Resource Unit, University of Kwa-Zulu Natal, Durban, South Africa.
authors: L A
authors: LA
authors: Bester
authors: Catalysis and Peptide Research Unit, School of Health Sciences, University of Kwa-Zulu Natal, Durban, South Africa.
authors: H G
authors: HG
authors: Kruger
authors: Catalysis and Peptide Research Unit, School of Health Sciences, University of Kwa-Zulu Natal, Durban, South Africa.
authors: T
authors: T
authors: Naicker
authors: Antimicrobial Research Unit, School of Health Sciences, University of Kwa-Zulu Natal, Durban, South Africa.
authors: S Y
authors: SY
authors: Essack
authors: Catalysis and Peptide Research Unit, School of Health Sciences, University of Kwa-Zulu Natal, Durban, South Africa.
authors: T
authors: T
authors: Govender
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D004755:Enterobacteriaceae / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D000077731:Meropenem; D008670:Metals / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D013845:Thienamycins / Q000494:pharmacology*; D065093:beta-Lactamase Inhibitors / Q000494:pharmacology*; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002614:Chelating Agents; D008670:Metals; D013845:Thienamycins; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases; D000077731:Meropenem
keywords: Carbapenem-resistant Enterobactericeae's; DPA; TPEN; metal chelating agents; metallo-β-lactamase