Antibacterial activity of colistin is resurrected by Stephania suberosa Forman extract against colistin-resistant Enterobacter cloacae

Abstract

To resurrect antibacterial efficacy of colistin (CLT), ceftazidime (CAZ) and cefotaxime (CTX), Stephania suberosa extract (SSE) was combined with these particular antibiotics to combat CLT-resistant Enterobacter cloacae (CREC) isolates. Disc diffusion assay showed that SSE inhibited E. cloacae strains with the dose-dependent manner. Minimum inhibitory concentrations (MICs) of SSE against all tested strains were 2000 µg ml^-1 . CREC DMST 37480 and 19719 were found to be resistant to CLT with MICs of 64 and 4 µg ml^-1 , respectively, and also resistant to CAZ. These strains showed a minimum bactericidal concentration (MBC) of SSE at 8000 µg ml^-1 . Checkerboard assay showed that CLT resistance was synergistically reversed by SSE against CREC DMST 37480 and 19719 with a fractional inhibitory concentration (FIC) indices of 0·253 and 0·265, respectively. Time-killing assay confirmed synergistic interaction by a decline in the viability combined treated group compared to an individual. CREC DMST 19719 was found to produce AmpC β-lactamase. SSE cannot resurrect CAZ in an AmpC producer. The scanning electron microscopy showed that SSE and CLT induced cell damages at different sites. GC-MS analysis identified 25 known Phyto-compounds. SSE and CLT combination could be further developed as a novel agent for treating multidrug-resistant CREC. SIGNIFICANCE AND IMPACT OF THE STUDY: Resistance to colistin (CLT), an alternative agent for treating multiple drug-resistant Enterobacter cloacae, is among the most serious, life-threatening issues. This study utilizes Stephania suberosa extract (SSE) to revive the antibacterial activity of colistin that has lost its antibacterial effectiveness in inhibiting E. cloacae. The findings support the development of the combined agent between SSE and colistin to conquer colistin-resistant E. cloacae.

Keywords: GC-MS analysis; Stephania suberosa Forman; colistin-resistant Enterobacter cloacae; fractional inhibitory concentration; synergistic activity; β-lactamase.