Binding and killing of bacteria by bismuth subsalicylate

Sharon Woods Technical Center, Procter and Gamble Company, Cincinnati, Ohio 45241.
Antimicrobial Agents and Chemotherapy (Impact Factor: 4.48). 01/1990; 33(12):2075-82. DOI: 10.1128/AAC.33.12.2075
Source: PubMed


Bismuth subsalicylate (BSS) is a compound without significant aqueous solubility that is widely used for the treatment of gastrointestinal disorders. BSS was able to bind bacteria of diverse species, and these bound bacteria were subsequently killed. A 4-log10 reduction of viable bacteria occurred within 4 h after a 10 mM aqueous suspension of BSS was inoculated with 2 x 10(6) Escherichia coli cells per ml. Binding and killing were dependent on the levels of inoculated bacteria, and significant binding but little killing of the exposed bacteria occurred at an inoculum level of 2 x 10(9) E. coli per ml. Intracellular ATP decreased rapidly after exposure of E. coli to 10 mM BSS and, after 30 min, was only 1% of the original level. Extracellular ATP increased after exposure to BSS, but the accumulation of extracellular ATP was not sufficient to account for the loss of intracellular ATP. The killing of bacteria exposed to BSS may have been due to cessation of ATP synthesis or a loss of membrane integrity. Bactericidal activity of BSS was also investigated in a simulated gastric juice at pH 3. Killing of E. coli at this pH was much more rapid than at pH 7 and was apparently due to salicylate released by the conversion of BSS to bismuth oxychloride. It is proposed that the binding and killing observed for BSS contribute to the efficacy of this compound against gastrointestinal infections such as traveler's diarrhea.

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    • "Bismuth compounds (colloidal bismuth sub citrate and bismuth subsalicylate) may reduce the development of resistance to co-administered antibiotics (Goodwin et al., 1988) and are also effective at treating H. pylori strains with established resistance to other antibiotics (Midolo et al., 1999; Andersen et al., 2000). Bismuth compounds actions include a reduction in intracellular ATP levels (Sox and Olson, 1989) and interference with the activity of urease enzyme, a key enzyme of H. pylori (Lee, 1991; Romano and Cuomo, 2004). Also, they induce the formation of an ulcer-specific coagulum (Sandha et al., 1998), preventing acid back diffusion (Meurer and Bower, 2002) and inhibit protein and cell wall synthesis as well as membrane function (Bland et al., 2004; Meurer and Bower, 2002; Romano and Cuomo, 2004). "
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    ABSTRACT: Helicobacter pylori is a Gram-negative, microaerophilic spiral or motile rod that infects about half the world's population with a very high prevalence in the developing world. It is an important aetiological factor in the development of gastritis, peptic ulcer disease, gastric atrophy and B cell mucosa associated lymphoid tissue (MALT) lymphoma. H. pylori infection is responsible for a significant cause of morbidity and mortality imposing a major burden on health care systems world wide. The high prevalence of infection in the developing countries has been attributed to poor socioeconomic status and sanitation as well as an increased trend of antibiotic resistance. Antimicrobial chemotherapy (two antibiotics and a proton pump inhibitor) employed for the treatment of H. pylori infections has emerged as the most important means to resolve these infections. However, antimicrobial therapy is fraught with a number of inherent limitations such as resistance, cost of treatment, unavailability of drugs in rural areas and undesirable side effects necessitating the need to search for alternative approaches from natural sources including vegetables, honey and probiotics amongst others. These could form the basis of novel low cost, efficient, large-scale and alternative/complementary solutions with minimal side effects to decrease or eradicate H. pylori infections in the future.
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    • "Free and bound EPS samples exhibited similar spectral absorbances, with and without BisBAL treatment, indicating that BisBAL has a negligible effect on the homology of EPS constituents but decreases their quantities. EPS suppression suggests that BisBAL directly interferes with metabolic activity of B. diminuta similar to bismuth sub-salicylate or may chelate membrane bound enzymes (Domenico et al., 1999; Sox and Olsen, 1989). "
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    ABSTRACT: A 2:1 molar ratio preparation of bismuth with a lipophilic dithiol (3-dimercapto-1-propanol, BAL) significantly reduced extracellular polymeric substances (EPS) expression by Brevundimonas diminuta in suspended cultures at levels just below the minimum inhibitory concentration (MIC). Total polysaccharides and proteins secreted by B. diminuta decreased by approximately 95% over a 5-day period when exposed to the bismuth-BAL chelate (BisBAL) at near MIC (12 microM). Fourier-transform infrared spectroscopy (FTIR) suggested that a possible mechanism of biofilm disruption by BisBAL is the inhibition of carbohydrate O-acetylation. FTIR also revealed extensive homology between EPS samples with and without BisBAL treatment, with proteins, polysaccharides, and peptides varying predominantly only in the amount expressed. EPS secretion decreased following BisBAL treatment as verified by atomic force microscopy and scanning electron microscopy. Without BisBAL treatment, a slime-like EPS matrix secreted by B. diminuta resulted in biofouling and inefficient hydrodynamic backwashing of microfiltration membranes.
    Full-text · Article · Feb 2008 · Biotechnology and Bioengineering
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    • "Among Aeromonas species, amonabactin is the virulence-associated siderophore, while most species excrete enterobactin for iron scavenging (Massad, Arceneaux & Byers, 1991). Though bismuth-containing remedies have been in regular use for centuries, only recently has Bi 3+ been taken seriously as an antimicrobial agent (Sox & Olson, 1989; Manhart, 1990). The antimicrobial effects of Bi 3+ span a wide range of bacteria, affecting inhibition of bacterial growth at 2-10 mM, levels deemed therapeutically achievable in the digestive tract (Cornick, Silva & Gorbach, 1990; Manhart, 1990). "
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