In vitro synergic effect of ²-lapachone and isoniazid on the growth of Mycobacterium fortuitum and Mycobacterium smegmatis

Silva, Joás Lucas da; Mesquita, Amanda Rafaela Carneiro de; Ximenes, Eulália Azevedo

doi:10.1590/s0074-02762009000400008

Cited by 11 publications

(7 citation statements)

References 14 publications

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“…By REMA we observed that the minimum inhibitory concentration (MIC) of INH against M. smegmatis was 8 µg/mL, as reported earlier (13). To test if modified INH inhibits M. smegmatis, the bacteria were treated with the reaction mixture (INH acetylated with Rv2170 in vitro) to analyze its sensitivity towards acetylated INH.…”

Section: Isoniazid Treated With Rv2170 Protein Failed To Kill M Smegsupporting

confidence: 61%

“…Thus LCMS and HPLC analyses prove our hypothesis that Rv2170 effectively acetylates INH nullifying the drug toxicity. The breakdown products INA and AH were found to be non-toxic to the bacterium.INH has an MIC of 8 µg/mL against M. smegmatis [the surrogate organism for virulent MTB](13,14,29); employing REMA we have also obtained the same MIC value. We reasoned that if INH is rendered inactive by acetylation in vitro, treatment of the bacterium with this modified INH would not affect the viability of the bacteria at this concentration.…”

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confidence: 60%

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Acetylation of isoniazid - a novel mechanism of isoniazid resistance inMycobacterium tuberculosis

Arun

Madhavan

Abraham

et al. 2020

Preprint

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Section: Isoniazid Treated With Rv2170 Protein Failed To Kill M Smegsupporting

confidence: 61%

mentioning

confidence: 60%

Acetylation of isoniazid - a novel mechanism of isoniazid resistance inMycobacterium tuberculosis

Arun

Madhavan

Abraham

et al. 2020

Preprint

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“…The interaction between β-lap and antimicrobial drugs has been characterized in other organisms, such as Mycobacterium sp. [33] and Fig. 8 The influence of β-lapachone alone or in combination with fluconazole on PDR5 mRNA expression of Pdr5p+ cells was assessed by RT-PCR.…”

Section: Discussionmentioning

confidence: 99%

β-Lapachone enhances the antifungal activity of fluconazole against a Pdr5p-mediated resistant Saccharomyces cerevisiae strain

et al. 2020

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Objectives The aim of this study was to evaluate the ability of lapachones in disrupting the fungal multidrug resistance (MDR) phenotype, using a model of study which an azole-resistant Saccharomyces cerevisiae mutant strain that overexpresses the ATPbinding cassette (ABC) transporter Pdr5p. Methods The evaluation of the antifungal activity of lapachones and their possible synergism with fluconazole against the mutant S. cerevisiae strain was performed through broth microdilution and spot assays. Reactive oxygen species (ROS) and efflux pump activity were assessed by fluorometry. ATPase activity was evaluated by the Fiske and Subbarow method. The effect of βlapachone on PDR5 mRNA expression was assessed by RT-PCR. The release of hemoglobin was measured to evaluate the hemolytic activity of β-lapachone. Results α-nor-Lapachone and β-lapachone inhibited S. cerevisiae growth at 100 μg/ml. Only β-lapachone enhanced the antifungal activity of fluconazole, and this combined action was inhibited by ascorbic acid. β-Lapachone induced the production of ROS, inhibited Pdr5p-mediated efflux, and impaired Pdr5p ATPase activity. Also, β-lapachone neither affected the expression of PDR5 nor exerted hemolytic activity. Conclusions Data obtained indicate that β-lapachone is able to inhibit the S. cerevisiae efflux pump Pdr5p. Since this transporter is homologous to fungal ABC transporters, further studies employing clinical isolates that overexpress these proteins will be conducted to evaluate the effect of β-lapachone on pathogenic fungi.

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“…Euclea species (Ebenaceae) have been found to be inhibitors of M. tuberculosis growth (189)(190). The activity of 2-hydroxynaphthoquinone (lawsone) has already been discussed earlier in this review.…”

Section: Several Naphthoquinones Isolated Mainly Frommentioning

confidence: 92%

Antimycobacterials from natural sources: ancient times, antibiotic era and novel scaffolds

et al. 2012

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Mycobacteria are a group of aerobic, non-motile, acid fast bacteria that have a characteristic cell wall composed of a mycolyl-arabinogalactan-peptidoglycan complex. They display different phenotypic attributes in their growth, color and biochemistry. Tuberculosis (TB) is defined as the infection with Mycobacterium tuberculosis complex and was declared a global health emergency principally because of the appearance of multidrug-resistant strains and the associated risk of infection in immune-compromised population. There is an urgent clinical need for novel, potent and safe anti-TB drugs. Natural products have been used since antiquity for treating diverse complaints and novel pharmacophores are discovered every year. Two of the most potent used antimycobacterials, the rifamycins and streptomycin, were first detected in Streptomyces bacteria. Plants are also the source of an exquisite variety of antimicrobials that can lead to useful therapeutics in the future. In this review, natural preparations used since antiquity for treating tuberculosis are described, together with a rapid view of the 20th century antibiotic development against TB. Finally a summary of the most potent recent natural antimycobacterials is displayed.

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In vitro synergic effect of ²-lapachone and isoniazid on the growth of Mycobacterium fortuitum and Mycobacterium smegmatis

Cited by 11 publications

References 14 publications

Acetylation of isoniazid - a novel mechanism of isoniazid resistance inMycobacterium tuberculosis

Acetylation of isoniazid - a novel mechanism of isoniazid resistance inMycobacterium tuberculosis

β-Lapachone enhances the antifungal activity of fluconazole against a Pdr5p-mediated resistant Saccharomyces cerevisiae strain

Antimycobacterials from natural sources: ancient times, antibiotic era and novel scaffolds

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