Influence of carbonyl cyanide m-chlorophenyl hydrazone on biofilm dynamics, protease, and siderophore production by Burkholderia pseudomallei.

Efflux pump inhibitors are a potential therapeutic strategy for managing antimicrobial resistance and biofilm formation. This article evaluated the effect of carbonyl cyanide m-chlorophenyl hydrazone (CCCP) on the biofilm growth dynamics and the production of virulence factors by Burkholderia pseudomallei. The effects of CCCP on planktonic, growing, and mature biofilm, interaction with antibacterial drugs, and protease and siderophore production were assessed. CCCP MICs ranged between 128 and 256 µM. The CCCP (128 µM) had a synergic effect with all the antibiotics tested against biofilms. Additionally, CCCP reduced (p < .05) the biomass of biofilm growth and mature biofilms at 128 and 512 µM, respectively. CCCP also decreased (p < .05) protease production by growing (128 µM) and induced (p < .05) siderophore release by planktonic cells (128 µM) growing biofilms (12.8 and 128 µM) and mature biofilms (512 µM). CCCP demonstrates potential as a therapeutic adjuvant for disassembling B. pseudomallei biofilms and enhancing drug penetration.

Effect of promethazine on biofilms of gram-positive cocci associated with infectious endocarditis.

This study evaluated the antimicrobial activity of promethazine against Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus mutans and its effect on the antimicrobial susceptibility of biofilms grown in vitro and ex vivo on porcine heart valves. Promethazine was evaluated alone and in combination with vancomycin and oxacillin against Staphylococcus spp. and vancomycin and ceftriaxone against S. mutans in planktonic form and biofilms grown in vitro and ex vivo. Promethazine minimum inhibitory concentration range was 24.4-95.31 µg/mL and minimum biofilm eradication concentration range was 781.25-3.125 µg/mL. Promethazine interacted synergistically with vancomycin, oxacillin and ceftriaxone against biofilms in vitro. Promethazine alone reduced (p < 0.05) the CFU-counts of biofilms grown on heart valves for Staphylococcus spp., but not for S. mutans, and increased (p < 0.05) the activity of vancomycin, oxacillin and ceftriaxone against biofilms of Gram-positive cocci grown ex vivo. These findings bring perspectives for repurposing promethazine as adjuvant in the treatment of infective endocarditis.

Mini-review: from in vitro to ex vivo studies: an overview of alternative methods for the study of medical biofilms.

Microbial biofilms are a natural adaptation of microorganisms, typically composed of multiple microbial species, exhibiting complex community organization and cooperation. Biofilm dynamics and their complex architecture are challenging for basic analyses, including the number of viable cells, biomass accumulation, biofilm morphology, among others. The methods used to study biofilms range from in vitro techniques to complex in vivo models. However, animal welfare has become a major concern, not only in society, but also in the academic and scientific field. Thus, the pursuit for alternatives to in vivo biofilm analyses presenting characteristics that mimic in vivo conditions has become essential. In this context, the present review proposes to provide an overview of strategies to study biofilms of medical interest, with emphasis on alternatives that approximate experimental conditions to host-associated environments, such as the use of medical devices as substrata for biofilm formation, microcosm and ex vivo models.