Preserving the Lifesaving Power of Antimicrobial Agents

Infectious Diseases Society of America, Arlington, Virginia, USA.
JAMA The Journal of the American Medical Association (Impact Factor: 29.98). 02/2011; 305(10):1027-8. DOI: 10.1001/jama.2011.279
Source: PubMed
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    ABSTRACT: A computational, comparative genomics workflow was defined for the identification of novel therapeutic candidates against Salmonella Typhimurium LT2, with the aim that the selected targets should be essential to the pathogen, and have no homology with the human host. Bioinformatics analysis identified 43 proteins as non-host essential, which could serve as potential drug and vaccine targets. Additional prioritization parameters characterized 13 proteins as vaccine candidates while druggability of each of the identified proteins was evaluated by the Drug Bank database prioritized same number proteins suitable for drug targets. As a case study we built a homology model of one of the potential drug targets MurD ligase using MODELLER (9v12) software. The model has been further explored for in silico docking study with the inhibitors having druggability potential from the Drug Bank database. Results from this study could facilitate selective S. Typhimurium LT2 proteins for drug design and vaccine production pipelines. Copyright © 2015. Published by Elsevier Ltd.
    Journal of Theoretical Biology 01/2015; 369. DOI:10.1016/j.jtbi.2015.01.022 · 2.35 Impact Factor
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    ABSTRACT: This study was in continuation of our earlier efforts in identifying phyto-derived agents as potential source for curing plasmid-mediated antibiotic resistance. Aqueous and methanol extracts of Alpinia galanga rhizomes were tried against multiple drug resistant (MDR) clinical isolates of Enterococcus faecalis, Staphylococcus aureus, Salmonella typhi, Shigella sonnei, as well as reference plasmid-harboring strains of Escherichia coli (RP4) and Bacillus subtilis (pUB110). Methanol extract exhibited bactericidal activities against reference plasmid harboring strains E. coli, B. subtilis and clinical isolate S. sonnei at 1200, 800 and 1200 μg/ml, respectively. Aqueous extract could not inhibit the growth of any pathogenic strain up to 1200 μg/ml concentrations. However, both the extracts were highly effective in curing plasmid-encoded antibiotic resistance in bacterial strains of clinical origin. Methanol extract showed plasmid curing at a much lower (400 μg/ml) concentration as compared to the aqueous extract (1200 μg/ml) and against wider range of clinical isolates. Methanol extracts showed a very high (98%) plasmid curing efficiency against S. typhi, followed by 50, 42 and 22 percent curing efficiencies against E. faecalis, S. aureus and S. sonnei respectively. Aqueous extract also showed noticeable antibiotic resistance reversal activities against R-plasmid harboring strains of clinical origin- E. faecalis, S. aureus and S. typhi with curing efficiencies of 72%, 70% and 12% respectively. The elimination of R-plasmids reversed the multiple antibiotic resistances in cured derivatives making them sensitive to low concentrations of antibiotics. Both the extracts seem to be potential source for controlling the development and spread of plasmid-borne multiple antibiotic resistance.
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    ABSTRACT: Since their development over 60 years ago, antimicrobials have become an integral part of healthcare practice worldwide. Recently, this has been put in jeopardy by the emergence of widespread antimicrobial resistance, which is one of the major problems facing modern medicine. In the past, the development of new antimicrobials kept us one step ahead of the problem of resistance, but only three new classes of antimicrobials have reached the market in the last thirty years. A time is therefore approaching when we may not have effective treatment against bacterial infections, particularly for those that are caused by Gram-negative organisms. An important strategy to reduce the development of antimicrobial resistance is to use antimicrobials more appropriately, in ways that will prevent resistance. This involves a consideration of the pharmacokinetic and pharmacodynamics properties of antimicrobials, the possible use of combinations, and more appropriate choice of antimicrobials, which may include rapid diagnostic testing and antimicrobial cycling. Examples given in this review include Mycobacterium tuberculosis, Gram-negative and Gram-positive organisms. We shall summarise the current evidence for these strategies and outline areas for future development.

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May 30, 2014