Reduction of capsular polysaccharide and potentiation of aminoglycoside inhibition in gram-negative bacteria by bismuth subsalicylate

Abstract

Bismuth subsalicylate (BSS), sodium salicylate, and bismuth nitrate were compared with respect to their effects on capsular polysaccharide (CPS) production, bacterial growth inhibition, and potentiation of aminoglycoside inhibition on strains of Gram-negative bacteria. At 250 microM, BSS reduced CPS production in Klebsiella pneumoniae cultures by greater than 90% in contrast to a 36% reduction by salicylate. At 500 microM, salicylate reduced CPS by 52%, versus a 70% reduction by bismuth nitrate. Substantial reduction of CPS production by BSS occurred before bacterial growth inhibition was observed. However, BSS at 250 microM decreased cell viability by 21%, and at 1 mM by 50%. Bismuth nitrate was equally inhibitory to cell growth. Salicylate at 1 mM did not affect bacterial cell counts. The susceptibility of selected Gram-negative bacteria to aminoglycoside antibiotics was studied in the presence of BSS or salicylate. Generally, salicylate at 2.5 mM reduced the concentration of aminoglycoside required to inhibit culture growth for 24 h (IC24) by two-fold. In contrast, 700 microM BSS reduced the IC24 for amikacin four-fold for a resistant K. pneumoniae strain. At 500 microM, BSS reduced the IC24 of gentamicin seven-fold for Salmonella typhimurium. Inhibitory concentrations of amikacin or tobramycin for Enterobacter cloacae or Serratia marcescens were also reduced seven-fold with 500 microM BSS. Bismuth nitrate reduced the IC24 of tobramycin by four-fold for E. cloacae. Thus, the profound effects of BSS on CPS production and aminoglycoside potentiation were due to the additive effects of bismuth and salicylate ions, whilst its effects on growth inhibition were due to the bismuth ion.