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Silver Antibacterial Synergism Activities with Eight Other Metal(loid)-Based Antimicrobials against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus.

ABSTRACT: The present study surveys potential antibacterial synergism effects of silver nitrate with eight other metal or metalloid-based antimicrobials (MBAs), including silver nitrate, copper (II) sulfate, gallium (III) nitrate, nickel sulfate, hydrogen tetrachloroaurate (III) trihydrate (gold), aluminum sulfate, sodium selenite, potassium tellurite, and zinc sulfate. Bacteriostatic and bactericidal susceptibility testing explored antibacterial synergism potency of 5760 combinations of MBAs against three bacteria (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus) in three different media. Silver nitrate in combination with potassium tellurite, zinc sulfate, and tetrachloroaurate trihydrate had remarkable bactericidal and bacteriostatic synergism effects. Synergism properties of MBAs decreased effective antibacterial concentrations remarkably and bacterial cell count decreased by 8.72 log10 colony-forming units (CFU)/mL in E. coli, 9.8 log10 CFU/mL in S. aureus, and 12.3 log10 CFU/mL in P. aeruginosa, compared to each MBA alone. Furthermore, most of the MBA combinations inhibited the recovery of bacteria; for instance, the combination of silver nitrate-tetrachloroaurate against P. aeruginosa inhibited the recovery of bacteria, while three-fold higher concentration of silver nitrate and two-fold higher concentration of tetrachloroaurate were required for inhibition of recovery when used individually. Overall, higher synergism was typically obtained in simulated wound fluid (SWF) rather than laboratory media. Unexpectedly, the combination of A silver nitrate-potassium tellurite had antagonistic bacteriostatic effects in Luria broth (LB) media for all three strains, while the combination of silver nitrate-potassium tellurite had the highest bacteriostatic and bactericidal synergism in SWF. Here, we identify the most effective antibacterial MBAs formulated against each of the Gram-positive and Gram-negative pathogen indicator strains.

SUBMITTER: Pormohammad A

PROVIDER: S-EPMC7760997 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Silver Antibacterial Synergism Activities with Eight Other Metal(loid)-Based Antimicrobials against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus.

Pormohammad Ali A Turner Raymond J RJ

Antibiotics (Basel, Switzerland) 20201128 12

The present study surveys potential antibacterial synergism effects of silver nitrate with eight other metal or metalloid-based antimicrobials (MBAs), including silver nitrate, copper (II) sulfate, gallium (III) nitrate, nickel sulfate, hydrogen tetrachloroaurate (III) trihydrate (gold), aluminum sulfate, sodium selenite, potassium tellurite, and zinc sulfate. Bacteriostatic and bactericidal susceptibility testing explored antibacterial synergism potency of 5760 combinations of MBAs against thre ...[more]

PMID: 33260495

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Project description:Bald's eyesalve is an Anglo-Saxon medicinal remedy that has been used through ancient times to treat eye sty infections and may represent a source of ancientbiotics. This study assessed the efficacy of Bald's eyesalve against several strains of Staphylococcus aureus and Pseudomonas aeruginosa, including a multi-drug resistant phenotype, and identified the principal compound conveying antibacterial activity. Bald's eyesalve formulations were produced by combining garlic, onion or leek, wine, bovine bile, and brass, with specific ingredient omissions in several formulations, followed by incubation at 4 °C for 9 days. Bald's eyesalve formulation ES-GBBr exhibited the greatest antibacterial activity against S. aureus and P. aeruginosa. Fractionation of ES-GBBr using molecular size exclusion and organic solvent partitioning isolated its antibacterial activity to the small molecule nonpolar fraction, and 1D 1H NMR revealed the identity of the antibacterial agent to be allicin. Depletion of allicin from this fraction by addition of exogenous cysteine established that all observable growth inhibition originated from allicin. Quantification of allicin demonstrated that its concentration was significantly greater in ES-GBBr compared to the ES-O formulation; however, this was not due to greater yield. The antibacterial activity of allicin against S. aureus was antagonized by other ingredients within Bald's eyesalve, whereas they were additive or synergistic against P. aeruginosa. These results suggest that neither leek nor onion is necessary for the antibacterial efficacy of Bald's eyesalve against S. aureus or P. aeruginosa, and while allicin was identified as the principal antibacterial agent present, its activity is influenced differentially in the presence of additional Bald's eyesalve ingredients when used against S. aureus compared to P. aeruginosa. Ancientbiotics may provide a source of promising antibacterials; however, identifying the source of activity and assessing distinct formulations for cooperative effects are essential to using ancient remedies, such as Bald's eyesalve, effectively against drug resistant pathogens.

Project description:Novel classes of antimicrobials are needed to address the emergence of multidrug-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). We have recently identified pyruvate kinase (PK) as a potential novel drug target based upon it being an essential hub in the MRSA interactome (Cherkasov, A., Hsing, M., Zoraghi, R., Foster, L. J., See, R. H., Stoynov, N., Jiang, J., Kaur, S., Lian, T., Jackson, L., Gong, H., Swayze, R., Amandoron, E., Hormozdiari, F., Dao, P., Sahinalp, C., Santos-Filho, O., Axerio-Cilies, P., Byler, K., McMaster, W. R., Brunham, R. C., Finlay, B. B., and Reiner, N. E. (2011) J. Proteome Res. 10, 1139-1150; Zoraghi, R., See, R. H., Axerio-Cilies, P., Kumar, N. S., Gong, H., Moreau, A., Hsing, M., Kaur, S., Swayze, R. D., Worrall, L., Amandoron, E., Lian, T., Jackson, L., Jiang, J., Thorson, L., Labriere, C., Foster, L., Brunham, R. C., McMaster, W. R., Finlay, B. B., Strynadka, N. C., Cherkasov, A., Young, R. N., and Reiner, N. E. (2011) Antimicrob. Agents Chemother. 55, 2042-2053). Screening of an extract library of marine invertebrates against MRSA PK resulted in the identification of bis-indole alkaloids of the spongotine (A), topsentin (B, D), and hamacanthin (C) classes isolated from the Topsentia pachastrelloides as novel bacterial PK inhibitors. These compounds potently and selectively inhibited both MRSA PK enzymatic activity and S. aureus growth in vitro. The most active compounds, cis-3,4-dihyrohyrohamacanthin B (C) and bromodeoxytopsentin (D), were identified as highly potent MRSA PK inhibitors (IC(50) values of 16-60 nM) with at least 166-fold selectivity over human PK isoforms. These novel anti-PK natural compounds exhibited significant antibacterial activities against S. aureus, including MRSA (minimal inhibitory concentrations (MIC) of 12.5 and 6.25 ?g/ml, respectively) with selectivity indices (CC(50)/MIC) >4. We also report the discrete structural features of the MRSA PK tetramer as determined by x-ray crystallography, which is suitable for selective targeting of the bacterial enzyme. The co-crystal structure of compound C with MRSA PK confirms that the latter is a target for bis-indole alkaloids. It elucidates the essential structural requirements for PK inhibitors in "small" interfaces that provide for tetramer rigidity and efficient catalytic activity. Our results identified a series of natural products as novel MRSA PK inhibitors, providing the basis for further development of potential novel antimicrobials.

Dataset Information

Silver Antibacterial Synergism Activities with Eight Other Metal(loid)-Based Antimicrobials against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus.

Publications

Silver Antibacterial Synergism Activities with Eight Other Metal(loid)-Based Antimicrobials against <i>Escherichia coli</i>, <i>Pseudomonas aeruginosa</i>, and <i>Staphylococcus aureus</i>.

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