Mycolic acid

Mycolic acid and arabinogalactan synthesis in mycobacteria 4.5 5-Fluorocytosine... 

Bacterial cell wall j3-Lactams Glyoopeptides Cycloserine Isoniazid Ethambutol Inhibit peptidoglycan synthesis Inhibit peptidoglycan synthesis Inhibits peptidoglycan synthesis Inhibits mycolic acid synthesis Inhibits arabinogalactan synthesis None in mammalian cells None in mammalian cells None in mammalian cells None in mammalian cells None in mammalian cells... 

The cell walls of mycobacteria contain three structures peptidoglycan, an arabinogalactan polysaccharide and long chain hydroxy fatty acids (mycolic acids) which are all covalently linked. Additional non-covalently attached lipid components found in the wall include glycolipids, various phospholipids and waxes. The lipid-rich nature of the mycobacterial wall is responsible for the characteristic acid-fastness on staining and serves as a penetration barrier to many antibiotics. Isoniazid and ethambutol have long been known as specific antimycobacterial agents but their mechanisms of action have only recently become more clearly understood. 

Characterization of individual mycolic acids in representative mycobacteria separation in 67... 

Kaneda, K. Molecular species analysis of mycolic acids in acid-fast bacteria. Iyo Masu Kenkyukai Koenshu 1987,12, 63-70. 

The answer is d. (Hardman, pp 1155-1159.) Only actively growing tubercle bacilli are susceptible to the bactericidal property of INI I. The major action of INI I is on the cell wall of the bacillus, where it prevents the synthesis of mycolic acid. 

Wick, L. Y., Wattiau, P. and Harms, H. (2002). Influence of the growth substrate on the mycolic acid profiles of mycobacteria, Environ. Microbiol., 4, 612-616. 

Bendinger, B., Rijnaarts, H. H. M., Altendorf, K. and Zehnder, A. J. B. (1993). Physicochemical cell-surface and adhesive properties of coryneform bacteria related to the presence and chain-length of mycolic acids, Appl. Environ. Microbiol., 59, 3973-3977. 

Gemaey, A. M., Minnikin, D. E., Copley, M. S., et al. (1999). Correlation of the occurrence of mycolic acids with tuberculosis prevalence in an archaeological population. In Tuberculosis Past and Present, eds. Palfi, G., Dutour, O., Deak, J., and Hutas, I., Szeged, Hungary, Golden Book Publisher Ltd. and Tuberculosis Foundation, pp. 275-282. 

Cyclopropyl fatty acids with C12, Cjg and C21 have been formed in many gram-negative and gram-positive bacteria [198]. The mycolic acid 142 (Cso) is a major component of the mycobacterial cell wall of the human strain of M. tuber-culosiSyEq. (57) [199]. 

Isoniazid, the hydrazide of isonicotinic acid was introduced into medical practice for treating tuberculosis in 1953. Isoniazid exhibits bactericidal action on Mycobacterium tuberculosis. It inhibits the synthesis of mycoUc acid, an important component of the cell membrane of mycobacteria. Mycolic acid is specific only to mycobacteria, and it is the cause of the selective toxicity of the drag with respect to these microorganisms. 

Isoniazid (INH) [Antitubercular Agent] Uses Rx prophylaxis of TB Action Bactericidal interferes w/ mycolic acid synth, disrupts cell wall Dose Adults. Active TB 5 mg/kg/24 h PO or IM (usually 300 mg/d) or DOT 15mg/kg... 

Fractionation of mycobacteria resulted in the identification of two cellular immunostimulatory components, trehalose dimycolate (TDM) and muramyl dipeptides (MDP). Both are normally found in association with the mycobacterial cell wall. TDM is composed of a molecule of trehalose (a disaccharide consisting of two molecules of a-D-glucose linked via an a 1-1 glycosidic bond), linked to two molecules of mycolic acid (a long-chain aliphatic hydrocarbon-based acid) found almost exclusively in association with mycobacteria. TDM, while retaining its adjuvanticity, is relatively non-toxic. 

Isoniazid (INH) is a synthetic derivative of isonico-tinic acid. It has bactericidal activity against both intra- and extra-cellular mycobacteria. It also displays anti-bacterial activity in caseous lesions, but only in proliferating cells. Losing genes which code for catalase and peroxidase is the major mechanism through which resistance occurs. Single mutations can rapidly result in such resistance if isoniazid is used alone. Its mechanism of action is presumably based on inhibition of the synthesis of mycolic acids, unique and essential components of the mycobacterial cell wall. 

Ethionamide is an analog of isoniazid and also inhibits mycolic acid synthesis. Its usefulness is limited by the rapid development of resistance. It can cause intense gastric pain and, like isoniazid, may also be neurotoxic. 

C) Inhibits KasA, a (3-ketoacyl carrier protein synthetase, thereby blocking mycolic acid synthesis... 

The most common mechanism of isoniazid resistance is the mycobacteria s formation of mutations in catalase-peroxidase KatG, the enzyme that is responsible for activation of isoniazid. Another resistance mechanism is through a missense mutation related to the inhA gene involved in mycolic acid biosynthesis. 

Ethionamide (Trecator) is a derivative of isonicotinic acid and is chemically related to isoniazid. It is a secondary agent used in combination when primary agents are ineffective or contraindicated it is a bacteriostatic antituberculosis agent. Its exact mechanism of action is unknown but is believed to involve inhibition of oxygen-dependent mycolic acid synthesis. It is thought that mutations in the region of the (tnhA) gene that are involved in mycolic acid synthesis can cause both isoniazid and ethionamide resistance. 

The answer is a. (Hardman, p 1157. Katzung, p 804.) Isoniazid inhibits mycobacterial cell-wall synthesis by inhibiting mycolic acid synthesis by a mechanism that is not fully understood. 

Isoniazid possibly exerts its action by inhibiting the synthesis of mycolic acid which is an essential component of mycobacterial cell wall. It is also postulated that the ability of isoniazid to suppress the formation of DNA and RNA and also inhibition of various oxidative mechanisms may be responsible for its action. 

It is chemically related to isoniazid and inhibit the synthesis of mycolic acids. It... 

Ethionamide is chemically related to isoniazid and also blocks the synthesis of mycolic acids. It is poorly water soluble and available only in oral form. It is metabolized by the liver. 

Isoniazid Inhibits synthesis of mycolic acids, an essential component of mycobacterial cell walls Bactericidal activity against susceptible strains of M tuberculosis First-line agent for tuberculosis treatment of latent infection less active against other mycobacteria Oral, IV hepatic clearance (half-life 1 h) reduces levels of phenytoin Toxicity Flepatotoxic, peripheral neuropathy (give pyridoxine to prevent)... 

Bacteria usually lack polyunsaturated fatty acids but often contain branched fatty acids, cyclopropane-containing acids, hydroxy fatty acids, and unesterified fatty acids. Mycobacteria, including the human pathogen Mycobacterium tuberculosis, contain mycolic acids. In these compounds the complex grouping R contains a variety of functional groups including -OH, -OCH3,... 

Clusters of arabinofuranosyl units at the nonreducing ends of the chains are esterified with mycolic acids (Section a,l).10 604 605 Mycobacteria also contain lipoarabinomannans that act as major antigens.603 606 Some mycobacterial species synthesize small glycopeptidolipids that may disrupt cell membranes of hosts.607 Mycobacteria don t produce toxins of usual types but cause slow, long-lasting infections. 

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