Mycobacterial strains

Amikacin is indicated for treatment of tuberculosis suspected to be caused by streptomycin-resistant or multidrag-resistant mycobacterial strains. To avoid emergence of resistance, amikacin should always be used in combination drug regimens. 

Capreomycin is a cyclic polypeptide complex antibiotic having a structure very much similar to viomycin, and produced by Streptomyces capreolus as a mixture of about four different components. It exerts its bacteriostatie aetion against certain mycobacterial strains, such as M. tuberculosis M. bovis M. kansasii, andM. avium by an unknown mechanism of action. However, its pharmacological and antibacterial activities are quite akin to the aminoglycosides. 

Fig. 6.23 The structure of mycolactone A/B. Mycolactone is an immunosuppressant toxin produced by selected pathogenic mycobacterial strains and is responsible for the formation of Buruli ulcers. A crucial role exists for a P450 in synthesis of the toxin. Mycolactone A/B is formed through the M. ulcerans CYP140A7-mediated C12 -...

Mycobacteria are generally considered to be of intermediate resistance to biocides, including aldehydes, between bacterial spores and other vegetative cells [90], Formalin, aqueous formaldehyde solution and glutaraldehyde are mycobactericidal, although some mycobacterial strains show increased resistance [90, 101, 236]. 

The advent of multidrug resistant strains of Mycobacterium tuberculosis (MDR-TB) has led to increased fears of untreatable infections by serious pathogens. Rifampicin, streptomycin and, occasionally, the quinolones are drugs used in the treatment of mycobacterial infections and resistance to those agents is as described previously. There... 

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]. 

Ethambutol is a water-soluble, heat-stable compound that acts by inhibition of arabinosyl transferase enzymes that are involved in cell wall biosynthesis. Nearly all strains of M tuberculosis and M. kansasii and most strains of Mycobacterium avium-intracellulare are sensitive to ethambutol. Drug resistance relates to point mutations in the gene (EmbB) that encodes the arabinosyl transferases that are involved in mycobacterial cell wall synthesis. 

A combination of trimethoprim-sulfamethoxazole is effective treatment for a wide variety of infections including P jiroveci pneumonia, shigellosis, systemic salmonella infections, urinary tract infections, prostatitis, and some nontuberculous mycobacterial infections. It is active against most Staphylococcus aureus strains, both methicillin-susceptible and methicillin-resistant, and against respiratory tract pathogens such as the pneumococcus, Haemophilus sp, Moraxella catarrhalis, and Klebsiella pneumoniae (but not Mycoplasma pneumoniae). However, the increasing prevalence of strains of E coli (up to 30% or more) and pneumococci that are resistant to trimethoprim-sulfamethoxazole must be considered before using this combination for empirical therapy of upper urinary tract infections or pneumonia. 

Rifampin, usually 600 mg/d (10 mg/kg/d) orally, must be administered with isoniazid or other antituberculous drugs to patients with active tuberculosis to prevent emergence of drug-resistant mycobacteria. In some short-course therapies, 600 mg of rifampin are given twice weekly. Rifampin 600 mg daily or twice weekly for 6 months also is effective in combination with other agents in some atypical mycobacterial infections and in leprosy. Rifampin, 600 mg daily for 4 months as a single drug, is an alternative to isoniazid prophylaxis for patients with latent tuberculosis only, who are unable to take isoniazid or who have had exposure to a case of active tuberculosis caused by an isoniazid-resistant, rifampin-susceptible strain. 

Susceptible strains of Mycobacterium tuberculosis and other mycobacteria are inhibited in vitro by ethambutol, 1-5 mcg/mL. Ethambutol inhibits mycobacterial arabinosyl transferases, which are encoded by the embCAB operon. Arabinosyl transferases are involved in the polymerization reaction of arabinoglycan, an essential component of the mycobacterial cell wall. Resistance to ethambutol is due to mutations resulting in overexpression of emb gene products or within the embB structural gene. 

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)... 

Detection of Rifampicin-Resistant Strains of Tuberculosis Rifampicin is an important antibiotic used to treat tuberculosis, as well as other mycobacterial diseases. 

Other monosaccharide components (of bacterial polysaccharides) that are structurally related to D-ribose include D-riburonic acid,232 identified in the exocellular polysaccharide produced by a strain of Rhizobium meliloti, and D-arabinose, frequently present as the furanose, in polysaccharides of mycobacterial cell-wall.233,234 L-Xylose235,236 should probably be included in the group, as it may be derived from D-arabinose through epimerization at C-4. Biosynthesis of these monosaccharides was not investigated. 

Susceptible strains of M tuberculosis and other mycobacteria are inhibited in vitro by ethambutol, 1-5 pgJmL. Ethambutol is an inhibitor of mycobacterial arabinosyl transferases, which are encoded... 

Other syntheses directed toward NGPs related to other mycobacterial glyco-lipids include those of the common inner-core trisaccharide fragment of the phenolic glycolipids of M. kansasii.154-155 In one of these syntheses,155 the tyramine moiety in the spacer-arm is suitable for conjugation to protein, and the trisaccharide segment in 112 has been prepared for the subsequent attachment of strain-specific terminal sugar residues.156-158... 

Multidrug-resistant M. tuberculosis (MDRTB) strains have become a problem. As pointed out previously, the mycobacterial cell wall presents a major barrier to the entry of chemotherapeutic drugs. Possible solutions are (i) to design drugs of increasing hydrophobicity that will pass through the cell wall, as with isoniazid derivatives [89, 90], (ii) to use a second antibiotic in combination with a known inhibitor of arabinogalactan or mycolic acid biosynthesis [238]. 

Microbiologists from Hong Kong have reported fonr cases of mycobacterial infections within 2 years (91). AH the patients had lesions at acnpnnctnre points. Acid-fast bacUh were present in two cases. Gene seqnencing identified the strain from two patients as Mycobacterium chelonae and from two patients as Mycobacterium nonchromogenium. 

Delipidated bacterial residues of human, bovine, avian, and saprophyte strains were active this can be explained by the fact that these residues contain, essentially, cell walls. It is known that mycobacterial cell-walls are mainly composed of three amino acids (alanine, glutamic acid, and a,e-diaminopimelic acid) linked to a polysaccharide containing arabinose, mannose, galactose, and muramic acid, -i and thus have an over-all composition very similar to that of the water-soluble part of the wax D of human strains. 

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