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Role of Plant-Based Bioflavonoids in Combating Tuberculosis
Published in Megh R. Goyal, Durgesh Nandini Chauhan, Assessment of Medicinal Plants for Human Health, 2020
Alka Pawar, Yatendra Kumar Satija
Ethambutol (EMB) mainly targets the synthesis of MTB cell wall by inhibiting polymerization of arabinogalactan, which is an essential constituent of cell wall. Additionally, it also impedes the consumption of the arabinose donor via hindering both the catalytic action of arabinosyl transferase and by forming the arabinose acceptor, or any of them.81 In MTB, the embCAB operon has demonstrated to be responsible for EMB resistance.74
Clinical Pharmacology of the Anti-Tuberculosis Drugs
Published in Lloyd N. Friedman, Martin Dedicoat, Peter D. O. Davies, Clinical Tuberculosis, 2020
Gerry Davies, Charles Peloquin
Ethambutol (ETH) is a water-soluble weak acid (log P −0.14, pKa 6.35/9.35, MW 204.31). The d-isomer is an inhibitor of mycobacterial cell wall arabinotransylferases leading to depletion of arabinogalactan and lipoarabinomannan. In vitro MIC99 for wild-type strains ranges from 0.5 to 4 μg/mL.3 The spontaneous rate of mutations conferring resistance is 1 in 107.4 Resistance is most commonly associated with mutations in the embB gene which codes for the major arabinosyltransferase enzyme and also embR and ubiA which modulate the activity of the arabinosyltransferase pathway.5
Mycobacterium tuberculosis – The Organism
Published in Peter D O Davies, Stephen B Gordon, Geraint Davies, Clinical Tuberculosis, 2014
This agent inhibits the enzyme arabinosyl transferase, which is involved in the synthesis of the major cell wall polysaccharide arabinogalactan. Acquisition of resistance is a multi step mutational process involving several genes in the embA, embB and embC gene cluster (principally embB), which code for this enzyme. A rather bizarre finding is that mutations in codon 306 of the embB gene not only impart resistance to ethambutol but predispose the bacterial cell to develop resistance to a range of anti-tuberculosis agents, thereby generating multidrug resistant strains [76]. There is only a weak association between resistance to isoniazid and ethambutol, although isoniazid-resistant strains with one particular mutation in the katG gene are more likely to acquire high-level resistance to ethambutol [77].
Ethambutol-induced optic neuropathy: Functional and structural changes in the retina and optic nerve
Published in Seminars in Ophthalmology, 2022
Sagnik Sen, Sohini Mandal, Mousumi Banerjee, Ranjitha Gk, Abhyuday Saxena, Swati Phuljhele Aalok, Rohit Saxena
A number of hypotheses have been postulated behind the ocular neurotoxic effect of EMB. The drug inhibits mycobacterial cell-wall synthesis by blocking arabinosyl-transferase.19 It interferes with the iron-containing complex I and copper-containing complex IV of mammalian mitochondrial DNA, resulting in the disruption of oxidative phosphorylation and mitochondrial dysfunction, with generation of reactive oxygen species (ROS) and resulting in tissue injury and cellular apoptosis.2,19 Increase in the mitochondrial membrane potential due to decrease in cytosolic calcium and increase in mitochondrial calcium has been also reported as a possible mechanism .20
The Genetics of Ethambutol-Induced Optic Neuropathy: A Narrative Review
Published in Neuro-Ophthalmology, 2022
Prabhjit Kaur, Sofia Singh, Kirandeep Kaur, Karthik Vinay Mahesh, Basavaraj Tigari, Vineet Sehgal, Aastha Takkar, Sahil Mehta, Ramandeep Singh, Samir Malhotra
As per the WHO guidelines, ethambutol is a first-line antimycobacterial drug and has been used for the treatment of tuberculosis in combination with rifampicin, isoniazid, and pyrazinamide since the 1960s. Being a bacteriostatic agent, ethambutol interferes with the arabinogalactan biosynthesis in the cell wall of multiplying bacilli and hence halts its growth.35 It is postulated that ethambutol inhibitis the embCAB operon of bacteria which encodes the arabinosyl transferase enzyme (involved in arabinogalactan biosynthesis).35,36 However, the underlying molecular mechanisms are still unclear.37
A Protective Role of Coenzyme Q10 in Ethambutol-Induced Retinal Ganglion Cell Toxicity: A Randomised Controlled Trial in Mice
Published in Neuro-Ophthalmology, 2022
Josiah Irma, Antonia Kartika, Mayang Rini, Bambang Setiohadji, Jonathan Salim
Ethambutol is a necessary treatment for TB. It enters the bacteria and acts as bacteriostatic agent by inhibiting arabinosyltransferase synthesis and function.20–22 Accumulated mycolic acid and trehalose isomers from this inhibition interfere with MTB cell wall and cell division and tag the bacteria for destruction by immune cells.20,23