3 research outputs found
In vitro potentiation of carbapenems with tannic acid against carbapenemaseâproducing enterobacteriaceae : exploring natural products as potential carbapenemase inhibitors
AIMS : We hypothesized and confirmed that tannic acid (TA) reverses carbapenem resistance by inhibiting carbapenemases in class A and B carbapenemaseâproducing Enterobacteriaceae.
METHODS AND RESULTS: Minimum inhibitory concentrations of carbapenems in the presence and absence of TA and other efflux pump inhibitors, TAâcarbapenemases inhibition assays and computational studies showed that TA had the greatest effect on metalloâÎČâlactamases (MBLs) followed by class A serineâÎČâlactamases (SBLs). TA completely reversed the MICs of MBL producers from between 32 and â„512 mg lâ1 to susceptible values (512 mg lâ1 to <4 to 16 mg lâ1. Tolerable cytotoxic effect was observed for the concentrations tested (8â1024 mg lâ1). TA inhibited enzymes with a marked difference of â50% inhibition (IC50) for NDMâ1 (270 ÎŒmol lâ1) and KPCâ2 (15 ÎŒmol lâ1).
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 VIMâ1 (â43·7220 ± 0·4513 kcal molâ1) and NDMâ1(â44·2329 ± 0·3806 kcal molâ1), interact with a larger number of their catalytic activeâsite residues than that of OXAâ48 (â22·5275 ± 0·1300 kcal molâ1) and KPCâ2 (â22·1164 ± 0·0111 kcal molâ1).
SIGNIFICANCE AND IMPACT OF THE STUDY : Tannic acid or its analogues could be developed into carbapenemaseâinhibiting adjuvants to restore carbapenem activity in CRE infections, save many lives and reduce healthcare associated costs.College of Health Sciences, University of KwaâZulu Natal, Durban, South Africa and the South African National Research Foundation (NRF).http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1365-26722020-02-01hj2019Medical Microbiolog