BRODIMOPRIM - EFFECTS OF SUBMINIMAL INHIBITORY CONCENTRATIONS ON VIRULENCE TRAITS OF RESPIRATORY AND URINARY-TRACT PATHOGENS, AND ON PLASMID TRANSFER AND STABILITY

The effect of brodimoprim, a new trimethoprim analogue, on several vir ulence traits of respiratory and urinary tract pathogens exposed to su b-lethal levels of the drug was studied. Adherence to tracheal epithel ial cells was inhibited by brodimoprim in Klebsiella pneumoniae (41-67 % reduction), Moraxella catarrhalis (87-90%) and Haemophilus influenza e (0-53%), while in Streptococcus pneumoniae binding was unaffected. W ith buccal epithelial cells the comparison between treated and control bacteria indicated statistically significant reduction in adherence w ith 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 level of the new agent. The drug affected protease and P-hemol ysin (a-toxin) production in both oxacillin-susceptible and -resistant S.aureus. On the contrary, synthesis of lipase, DNase, coagulase, and p-lactamase (S.aureus), pneumolysin (S.pneumoniae), streptolysin S, D Nase, and protease (S.pyogenes), capsule (K.pneumoniae, H.influenzae a nd S.pneumoniae), and p-lactamase (K.pneumoniae, H.influenzae and M.ca tarrhalis) were not inhibited by subminimal inhibitory concentrations (sub-MICs) of the drug. Finally, motility was blocked in urinary patho gens E.coli, P.mirabilis and P.aeruginosa, while in this latter microo rganism pigment production was also affected. High molecular weight lo w-copy F'lac, and low molecular weight high-copy pHSG298 plasmids were eliminated from E.coli treated with sub-MIG concentrations of brodimo prim. 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 conjugat ion was carried out with bacteria exposed to brodimoprim (5XMIC), a re duction (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-MIG le vels may assist the drug in eradicating respiratory pathogens from the epithelial lining, thus diminishing the probability of reinfection.