Protection of
            <i>Escherichia coli</i>
            from Isoniazid Inhibition

Tritz, Gerald J.

doi:10.1128/aac.5.3.217

Cited by 3 publications

(2 citation statements)

References 26 publications

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“…Although the MOA is still unclear, the peroxidative activation of isoniazid by the mycobacterial enzyme KatG forms potent inhibitors of lipid and nucleic acid biosynthesis, as well as inducing oxidative stress [53]. Regardless, its inhibitory effect on E. coli has long been reported as being dependent on the initial cell concentration, antibiotic concentration, and medium composition [54], and experimentally confirmed (Table 1). Apparently, the metabolic fingerprint detected with FTIR spectroscopy more closely reflects the inhibition of DNA biosynthesis; however, further validation of this observation is required.…”

Section: Differentiating the Other Metabolic Fingerprintsmentioning

confidence: 95%

Metabolic Fingerprinting with Fourier-Transform Infrared (FTIR) Spectroscopy: Towards a High-Throughput Screening Assay for Antibiotic Discovery and Mechanism-of-Action Elucidation

2020

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The discovery of antibiotics has been slowing to a halt. Phenotypic screening is once again at the forefront of antibiotic discovery, yet Mechanism-Of-Action (MOA) identification is still a major bottleneck. As such, methods capable of MOA elucidation coupled with the high-throughput screening of whole cells are required now more than ever, for which Fourier-Transform Infrared (FTIR) spectroscopy is a promising metabolic fingerprinting technique. A high-throughput whole-cell FTIR spectroscopy-based bioassay was developed to reveal the metabolic fingerprint induced by 15 antibiotics on the Escherichia coli metabolism. Cells were briefly exposed to four times the minimum inhibitory concentration and spectra were quickly acquired in the high-throughput mode. After preprocessing optimization, a partial least squares discriminant analysis and principal component analysis were conducted. The metabolic fingerprints obtained with FTIR spectroscopy were sufficiently specific to allow a clear distinction between different antibiotics, across three independent cultures, with either analysis algorithm. These fingerprints were coherent with the known MOA of all the antibiotics tested, which include examples that target the protein, DNA, RNA, and cell wall biosynthesis. Because FTIR spectroscopy acquires a holistic fingerprint of the effect of antibiotics on the cellular metabolism, it holds great potential to be used for high-throughput screening in antibiotic discovery and possibly towards a better understanding of the MOA of current antibiotics.Metabolites 2020, 10, 145 2 of 15 of finding compounds with unique biological and/or chemical properties and limited insight in the pharmacological target. Additionally, phenotypic screening does not explore the chemical grey matter, i.e., compounds capable of inducing some level of phenotypic modulation, but without sufficient potency to induce cell death or growth inhibition, which can be a source of compounds suitable for lead optimization with medicinal chemistry techniques [5,6]. Antibiotic discovery is a very challenging task, but identifying the MOA has proven equally challenging [7]. Currently, determining the MOA of antibiotics is still a bottleneck of the phenotypic screening discovery process, for which metabolomics holds great potential. As such, the ability to rapidly infer MOA and, if possible, the biomolecular target of antibiotics is increasingly important given the pressing need for new antibiotics. Currently, screening hundreds of thousands of compounds is a reasonable throughput of a drug discovery program, in part due to the ease in synthetizing bioactive compounds, and in part given the increasing availability of natural product libraries [8]. Two concepts are relevant when discussing MOA identification. One is determining the molecular pathways affected by a given compound:the drug effects. The second is the specific compound-substrate interactions:the drug target [9]. Although both concepts are very important in antibiotic discovery, given the exploratory purpo...

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Section: Differentiating the Other Metabolic Fingerprintsmentioning

confidence: 95%

Metabolic Fingerprinting with Fourier-Transform Infrared (FTIR) Spectroscopy: Towards a High-Throughput Screening Assay for Antibiotic Discovery and Mechanism-of-Action Elucidation

2020

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“…The activity of the isoniazid reported here disagrees a bit with that of Ladishav et al, though different strains of organisms were used. There has been some activity of isoniazid previously reported against E. coli and Staphylococcus aureus [27,28].…”

mentioning

confidence: 99%

In Silico Studies, Comparative Synthesis and Antibacterial Activity of Some Imine Derivatives of Isonicotinic Hydrazide

Agwom

2019

OMCIJ

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Reflux Method: A 0.005moles (0.6857g) of Isoniazid was completely dissolved in 15ml absolute ethanol and 0.005mole of the Aldehyde (Vanillin, Piperonaldehyde and 4-dimethylaminobenzaldehyde) was dissolved in another 15ml of absolute ethanol and added in drop wise to the Isoniazid solution. Then 4-6 drops of acetic acid were added, and the mixture was refluxed for 3hours at 95⁰C. The reaction was monitored using TLC. The solid crystals obtained was filtered and washed with ethanol.Stirring Method at Room Temperature: A 0.005moles (0.6857g) of Isoniazid was completely dissolved in 10ml 98% methanol and 0.005mole of the Aldehydes was dissolved in another 10ml of 98% methanol and added in drop wise to the Isoniazid solution with stirring. Then 4-6 drops of acetic acid were

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Preparation and In vitro Evaluation of Isoniazid-Containing Dex-HEMA-Co-PNIPAAm Nanogels

Jafari¹,

Kaffashi²

2015

CeN

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Protection of Escherichia coli from Isoniazid Inhibition

Cited by 3 publications

References 26 publications

Metabolic Fingerprinting with Fourier-Transform Infrared (FTIR) Spectroscopy: Towards a High-Throughput Screening Assay for Antibiotic Discovery and Mechanism-of-Action Elucidation

Metabolic Fingerprinting with Fourier-Transform Infrared (FTIR) Spectroscopy: Towards a High-Throughput Screening Assay for Antibiotic Discovery and Mechanism-of-Action Elucidation

In Silico Studies, Comparative Synthesis and Antibacterial Activity of Some Imine Derivatives of Isonicotinic Hydrazide

Preparation and In vitro Evaluation of Isoniazid-Containing Dex-HEMA-Co-PNIPAAm Nanogels

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