Brodimoprim: Effects of subminimal inhibitory concentrations on virulence traits of respiratory and urinary tract pathogens, and on plasmid transfer and stability

A. Marchese

Research output: Contribution to journalArticle

Abstract

The effect of brodimoprim, a new trimethoprim analogue, on several virulence traits of respiratory and urinary tract pathogens exposed to sub-lethal levels of the drug was studied. Adherence to tracheal epithelial cells was inhibited by brodimoprim in Klebsiella pneumoniae (41-67% reduction), Moraxella catarrhalis (87-90%) and Haemophilus influenzae (0-53%), while in Streptococcus pneumoniae binding was unaffected. With buccal epithelial cells the comparison between treated and control bacteria indicated statistically significant reduction in adherence with both S. pneumoniae and H. influenzae, (P <0.015). With M. catarrhalis and Streptococcus pyogenes only marginal changes were detected (P > 0.05). Exoenzyme and capsule production were assessed in at least three isolates of diverse respiratory pathogens grown in the presence of sub-lethal levels of the new agent. The drug affected protease and β-hemolysin (α-toxin) production in both oxacillin-susceptible and -resistant S. aureus. On the contrary, synthesis of lipase, DNase, coagulase, and β-lactamase (S. aureus), pneumolysin (S. pneumoniae), streptolysin S, DNase, and protease (S. pyogenes), capsule (K. pneumoniae, H. influenzae and S. pneumoniae), and β-lactamase (K. pneumoniae, H. influenzae and M. catarrhalis) were not inhibited by subminimal inhibitory concentrations (sub-MICs) of the drug. Finally, motility was blocked in urinary pathogens E. coli, P. mirabilis and P. aeruginosa, while in this latter microorganism pigment production was also affected. High molecular weight low-copy F'lac, and low molecular weight high-copy pHSG298 plasmids were eliminated from E. coli treated with sub-MIC concentrations of brodimoprim. The incidence of cured cells ranged from 9% for F'lac to 23% for pHSG298. F'lac transfer was also inhibited by the drug. When conjugation was carried out with bacteria exposed to brodimoprim (5XMIC), a reduction (50%) in the number of recombinants was noted in comparison to the control. The fact that brodimoprim interferes with the expression of some virulence traits, in particular with adherence, at sub-MIC levels may assist the drug in eradicating respiratory pathogens from the epithelial lining, thus diminishing the probability of reinfection.

Original languageEnglish
Pages (from-to)171-177
Number of pages7
JournalJournal of Chemotherapy
Volume8
Issue number3
Publication statusPublished - 1996

Keywords

  • bacterial adhesion
  • brodimoprim
  • in vitro activity
  • pathogenicity traits
  • plasmid transfer
  • respiratory pathogens
  • urinary pathogens

ASJC Scopus subject areas

  • Microbiology (medical)
  • Pharmacology (medical)

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