Efeito in vitro do quelante de ferro deferiprona sobre Burkholderia pseudomallei na forma planctônica e de biofilmes

Abstract

Burkholderia pseudomallei is an opportunistic pathogen with environmental origin causing melioidosis disease. It has already been demonstrated that the availability of iron favors some processes of this bacterium, such as the formation of biofilms. Thus, this study aimed to evaluate the effect of the iron chelator deferiprone (DFP) on antimicrobial sensitivity and the formation and maintenance of biofilms. The planktonic sensitivity to DFP alone and combined with the drugs was evaluated by the broth microdilution test, investigation of the effects of DFP on the formation of biofilms, evaluating its biomass through the crystal violet technique and the metabolic activity of the mature biofilm determined with resazurin. The minimal inhibitory concentration (MIC) of DFP was 4 – 64 µg/mL. Combined with antimicrobials, there was a reduction in MIC for amoxicillin/clavulanate (AMC) and meropenem (MER). DFP reduced (P<0.05) the biomass of the growing biofilm by 21 and 12% at MIC and MIC/2, respectively, while in the mature biofilm there was a reduction (P<0.05) by 47%, 59%, 52% and 30% at concentrations of 512, 256, 128 and 64 µg/mL, respectively. The DFP did not eradicate the biofilms of B. pseudomallei, not showing values of minimum eliminatory concentrations of the biofilm (MBEC) in the concentrations tested. As for antibacterial drugs, no MBEC values were found for AMC and the MBEC ranges for MER were 16 – 512 µg/mL and 256 – 512 µg/mL for doxycycline (DOX). When used at a concentration of 256 µg/mL, DFP did not reduce MBEC values for AMC, MER, and DOX against mature biofilms of B. pseudomallei. DFP inhibits the planktonic growth of B. pseudomallei potentiates the effect β-lactams against the bacteria in the planktonic form and reduces the biomass of biofilms in formation and of mature biofilms, without, however, eradicate mature biofilms of B. pseudomallei, nor sensitize them to AMC, MER, and DOX drugs.