title: Promethazine improves antibiotic efficacy and disrupts biofilms of Burkholderia pseudomallei.
abstract: Efflux pumps are important defense mechanisms against antimicrobial drugs and maintenance of Burkholderia pseudomallei biofilms. This study evaluated the effect of the efflux pump inhibitor promethazine on the structure and antimicrobial susceptibility of B. pseudomallei biofilms. Susceptibility of planktonic cells and biofilms to promethazine alone and combined with antimicrobials was assessed by the broth microdilution test and biofilm metabolic activity was determined with resazurin. The effect of promethazine on 48 h-grown biofilms was also evaluated through confocal and electronic microscopy. The minimum inhibitory concentration (MIC) of promethazine was 780 mg l-1, while the minimum biofilm elimination concentration (MBEC) was 780-3,120 mg l-1. Promethazine reduced the MIC values for erythromycin, trimethoprim/sulfamethoxazole, gentamicin and ciprofloxacin and reduced the MBEC values for all tested drugs (p<0.05). Microscopic analyses demonstrated that promethazine altered the biofilm structure of B. pseudomallei, even at subinhibitory concentrations, possibly facilitating antibiotic penetration. Promethazine improves antibiotics efficacy against B. pseudomallei biofilms, by disrupting biofilm structure.
authors.affiliation: a Specialized Center of Medical Micology , Federal University of Ceará , Fortaleza , Brazil.
authors.forename: José Júlio Costa
authors.initials: JJ
authors.lastname: Sidrim
authors.affiliation: a Specialized Center of Medical Micology , Federal University of Ceará , Fortaleza , Brazil.
authors.forename: David Caldas
authors.initials: DC
authors.lastname: Vasconcelos
authors.affiliation: a Specialized Center of Medical Micology , Federal University of Ceará , Fortaleza , Brazil.
authors.forename: Giovanna Barbosa
authors.initials: GB
authors.lastname: Riello
authors.affiliation: a Specialized Center of Medical Micology , Federal University of Ceará , Fortaleza , Brazil.
authors.forename: Glaucia Morgana de Melo
authors.initials: GM
authors.lastname: Guedes
authors.affiliation: a Specialized Center of Medical Micology , Federal University of Ceará , Fortaleza , Brazil.
authors.forename: Rosana
authors.initials: R
authors.lastname: Serpa
authors.affiliation: a Specialized Center of Medical Micology , Federal University of Ceará , Fortaleza , Brazil.
authors.forename: Tereza de Jesus Pinheiro Gomes
authors.initials: TJ
authors.lastname: Bandeira
authors.affiliation: b Department of Statistics and Applied Mathematics , Federal University of Ceará , Fortaleza , Brazil.
authors.forename: André Jalles
authors.initials: AJ
authors.lastname: Monteiro
authors.affiliation: a Specialized Center of Medical Micology , Federal University of Ceará , Fortaleza , Brazil.
authors.forename: Rossana de Aguiar
authors.initials: RA
authors.lastname: Cordeiro
authors.affiliation: a Specialized Center of Medical Micology , Federal University of Ceará , Fortaleza , Brazil.
authors.forename: Débora de Souza Collares Maia
authors.initials: DS
authors.lastname: Castelo-Branco
authors.affiliation: a Specialized Center of Medical Micology , Federal University of Ceará , Fortaleza , Brazil.|c Postgraduate Program in Veterinary Science , State University of Ceará , Fortaleza , Brazil.
authors.forename: Marcos Fábio Gadelha
authors.initials: MF
authors.lastname: Rocha
authors.affiliation: a Specialized Center of Medical Micology , Federal University of Ceará , Fortaleza , Brazil.
authors.forename: Raimunda Sâmia Nogueira
authors.initials: RS
authors.lastname: Brilhante
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D016957:Burkholderia pseudomallei / Q000187:drug effects* / Q000502:physiology; D004357:Drug Synergism; D008826:Microbial Sensitivity Tests; D010933:Plankton / Q000187:drug effects; D011398:Promethazine / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D011398:Promethazine
keywords: Burkholderia pseudomallei; biofilms; efflux pumps; promethazine; resistance; synergism