Efeito da fluoxetina sobre Burkholderia pseudomallei na forma planctônica e de biofilmes

Abstract

Melioidosis, caused by Burkholderia pseudomallei bacteria, is a disease of great importance to public health. B. pseudomallei, when in biofilms, tends to be more resistant to antibiotics, resulting in chronic infections. Thus, studies have been conducted in order to identify compounds that interfere with the dynamics of biofilms. Thus, studies have been conducted in order to identify compounds that interfere with the dynamics of biofilms. Thus, this study aimed to evaluate the in vitro effect of fluoxetine hydrochloride (FLU) on the planktonic and biofilm growth of B. pseudomallei and on the antimicrobial susceptibility of these bacteria. The planktonic sensitivity to FLU alone and in combination with antimicrobials was evaluated by the broth microdilution test. The effects of FLU on growing biofilm and on mature biofilms were investigated by evaluating the biomass by crystal violet staining technique and the metabolic activity of the biofilm determined with resazurin. The minimum inhibitory concentration (MIC) of FLU was 19.53 - 312.5 µg/mL. When combined with the antimicrobials, there was a significant increase in the MIC for meropenem (MER), while not changing the MICs of the other drugs. FLU altered the biomass of the growing biofilm at the concentration of MIC/4, while in the mature biofilm there was a reduction (P<0.05) 23 and 30% at concentrations of 625 and 1250 µg/mL, respectively. FLU eradicated the biofilms of B. pseudomallei, showing minimum biofilm eliminating concentration (MBEC) values at concentrations of 1250 - 2500 µg/mL. As for the antimicrobial drugs, no MBEC values were found for AMC and the MBEC ranges for MER were 16 - 256 µg/mL and >256 µg/mL for doxycycline (DOX). When used at MIC concentration (19.53 - 312.5 µg/mL), FLU did not reduce the MBEC values for AMC, MER and DOX against mature biofilms of Burkholderia pseudomallei, but when used at MBEC/4 concentration (312.5 and 625 µg/mL), there was a statistically significant reduction (P<0.05) for all combinations tested on mature biofilms of B. pseudomallei. FLU inhibits planktonic growth of B. pseudomallei, kills growing biofilms and mature biofilms, and sensitizes them to AMC, MER and DOX drugs.