In vitro potentiation of carbapenems with tannic acid against carbapenemase-producing enterobacteriaceae: exploring natural products as potential carbapenemase inhibitors.
J Appl Microbiol
; 126(2): 452-467, 2019 Feb.
Article
em En
| MEDLINE
| ID: mdl-30365206
ABSTRACT
AIMS:
We hypothesized and confirmed that tannic acid (TA) reverses carbapenem resistance by inhibiting carbapenemases in class A and B carbapenemase-producing Enterobacteriaceae. METHODS ANDRESULTS:
Minimum inhibitory concentrations of carbapenems in the presence and absence of TA and other efflux pump inhibitors, TA-carbapenemases inhibition assays and computational studies showed that TA had the greatest effect on metallo-ß-lactamases (MBLs) followed by class A serine-ß-lactamases (SBLs). TA completely reversed the MICs of MBL producers from between 32 and ≥512 mg l-1 to susceptible values (<4 mg l-1 ) while substantially reducing the MICs of SBLs from between 16 and >512 mg l-1 to <4 to 16 mg l-1 . Tolerable cytotoxic effect was observed for the concentrations tested (8-1024 mg l-1 ). TA inhibited enzymes with a marked difference of ≈50% inhibition (IC50 ) for NDM-1 (270 µmol l-1 ) and KPC-2 (15 µmol l-1 ).CONCLUSION:
TA inhibited both MBLs and SBLs by targeting their hydrophobic sites. Moreover, TA had a stronger binding affinity for MBLs than SBLs as the MBLs, specifically VIM-1 (-43·7220 ± 0·4513 kcal mol-1 ) and NDM-1(-44·2329 ± 0·3806 kcal mol-1 ), interact with a larger number of their catalytic active-site residues than that of OXA-48 (-22·5275 ± 0·1300 kcal mol-1 ) and KPC-2 (-22·1164 ± 0·0111 kcal mol-1 ). SIGNIFICANCE AND IMPACT OF THE STUDY Tannic acid or its analogues could be developed into carbapenemase-inhibiting adjuvants to restore carbapenem activity in CRE infections, save many lives and reduce healthcare associated costs.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Taninos
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Proteínas de Bactérias
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Carbapenêmicos
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Enterobacteriáceas Resistentes a Carbapenêmicos
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Antibacterianos
Idioma:
En
Revista:
J Appl Microbiol
Assunto da revista:
MICROBIOLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
África do Sul
País de publicação:
ENGLAND
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ESCOCIA
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GB
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GREAT BRITAIN
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INGLATERRA
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REINO UNIDO
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SCOTLAND
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UK
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UNITED KINGDOM