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A Rapid Assay to Screen for Resistance Modifying Activities of DNA Gyrase Inhibitors from Manure Compost Actinomycete Extracts
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| Author:
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ANIS MUHAMMAD, ROZAINI MOHD ZOHDI, SHARIFAH AMINAH SYED MOHAMAD, MOHD FAIZ FOONG ABDULLAH
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| Abstract:
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Bacteria have evolved rapidly especially in terms of defensive machineries to ensure their survival against therapeutic drugs. Alternative regimes are necessary to manage the rising multidrug-resistant superbugs. Drug synergism targeting bacterial resistant mechanism is an attractive strategy to address the global issue. In view of this, a rapid and targeted assay incorporating resazurin was developed to screen potential enhancers of first generation DNA gyrase inhibitors (nalidixic acid and novobiocin) from microbial extracts. The antibacterial activities of 191 manure compost actinomycete extracts were evaluated against three novobiocin and nalidixic acid resistant strains, Staphylococcus saprophyticus, Staphylococcus cohnii subsp. urealyticum and Staphylococcus xylosus ATCC 29971. The inactive extracts (90.1%) were further tested in combination with DNA gyrase inhibitors. Three extracts (G2B2, C2B6 and G2C32) exhibited consistent nalidixic acid enhancing potential while none was able to restore the activity of novobiocin. At a concentration of 1mg/ml, the extracts enhanced the inhibitory activity of nalidixic acid with a 100-fold reduction of the antibiotic’s MIC (0.1mg/ml). Furthermore, the stable reduction of resazurin to resorufin suggests the absence of an efflux pump activity, thus hinting a specific modifying action towards the mutated DNA gyrase. The results indicated the presence of resistant modifying agents from manure compost actinomycetes that can potentially restore the primary function of first generation DNA gyrase inhibitor
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| Keyword:
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Resistance modifying agents, DNA gyrase, Manure compost, actinomycetes
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| EOI:
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-
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| DOI:
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https://doi.org/10.31838/ijpr/2018.10.04.007
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| Download:
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