Mycobacteria, killing

Lysol consists of a mixture of the three cresol isomers solubilized using a soap prepared from linseed oil and potassium hydroxide, to form a clear solution on dilution. Most vegetative pathogens, including mycobacteria, are killed in 15 minutes by 0.3—0.6% lysol. Lysol has a phenol coefficient of 2. Bacterial spores are very resistant. Lysol is also the name of a proprietary product, the formula of which has changed over the years other phenols have been substituted for the cresols. 

Mycobacteria are also killed in vitro, as expected from an antibiotic sharing the properties of the rifamycin family [24], In a study by Soro et al. [25], the MIC of rifaximin was determined for five Mycobacterium tuberculosis isolates from patients with tuberculosis. MIC concentrations were studied at 6, 20, 90 and 270 pg/ml, respectively. No resistant organisms were found. Growing M. tuberculosis in the presence of varying doses of rifaximin did not induce the occurrence of rifampicin-resistant strains [25]. In addition to this, experimental tubercular infection in the guinea pig was found not to be affected by an oral treatment course with rifaximin, therefore confirming the lack of absorption of the molecule after oral administration [26],... 

Figure 17.33 Killing of myobacteria within a macrophage. Cytokines from ThI cells stimulate fusion of the phagosome, in which myobacteria thrive, with the lysosome, so that the mycobacteria are killed within the phagolysosome by the agents described above.

Rifampin binds to the 3 subunit of bacterial DNA-dependent RNA polymerase and thereby inhibits RNA synthesis. Resistance results from any one of several possible point mutations in rpoB, the gene for the 3 subunit of RNA polymerase. These mutations result in reduced binding of rifampin to RNA polymerase. Human RNA polymerase does not bind rifampin and is not inhibited by it. Rifampin is bactericidal for mycobacteria. It readily penetrates most tissues and penetrates into phagocytic cells. It can kill organisms that are poorly accessible to many other drugs, such as intracellular organisms and those sequestered in abscesses and lung cavities. 

Iodophors are complexes of iodine with a surface-active agent such as polyvinyl pyrrolidone (PVP povidone-iodine). Iodophors retain the activity of iodine. They kill vegetative bacteria, mycobacteria, fungi, and lipid-containing viruses. They may be sporicidal upon prolonged exposure. Iodophors can be used as antiseptics or disinfectants, the latter containing more iodine. The amount of free iodine is low, but it is released as the solution is diluted. An iodophor solution must be diluted according to the manufacturer s directions to obtain full activity. 

Most popular adjuvants are the incomplete and the complete forms of Freund. The incomplete adjuvant is a water-in-oil emulsion by which the antigen is slowly released, providing a long period of contact between antigen and immune system. The complete adjuvant contains heat-killed Mycobacteria that causes a local injury and granuloma formation, thus providing a nonspecific stimulus. 

Mycobacteria. Most mycobacterial species seem to be harmless saprophytic soil bacteria of the grampositive group. However, tuberculosis (caused by Mycobacterium tuberculosis) may infect one-third of the inhabitants of the earth603 and kills about three million... 

Disinfectants are used in industrial establishments, hospitals, and homes to prevent infection. Common disinfectants can kill some fungi, lipid-containing viruses, gram-negative bacteria, and mycobacteria, but bacterial spores are resistant to disinfectants. Factors affecting the effectiveness of disinfectants are contact line, concentration, pH, and the presence of interfering substances such as lipids, rubber, or plastics. 

The presence of heat-killed mycobacteria in Freund s complete adjuvant serves to generally stimulate the entire reticuloendothelial system of the test animal. In addition, there is some evidence these dead celts also stimulate T lymphocyte proliferation and their production of B cell-stimulating factors. Use of the complete adjuvant is recommended for the first dose of immunogen but incomplete adjuvant is adequate for subsequent injections. 

The antimicrobial properties of silver and its salts have been discussed in various books [14, 16-18] and particular reference must be made to Grier s review in 1983 [15]. Ag usually used in the form of silver nitrate, is bacteriostatic or bactericidal [19-29], antifungal [30-32], protozoicidal [33] and lethal to herpes simplex virus [34]. However, bacterial spores [19], cysts of Entamoeba histolytica [19] and mycobacteria [35] are not killed by Ag. Brown and Anderson [20] observed a non-linear order of death in Pseudomonas aeruginosa exposed to Ag, whereas Ricketts et al. [22] reported a rapid bactericidal action of Ag in water, but not in broth, at concentrations of silver nitrate of 0.5 and 1 pg/ml (2.9 x 10 and 5.8 x 10 M, respectively) with inactivation at concentrations above 1 p.g/ml being too fast for measurement. 

Pyrazinamide is a derivative of nicotinamide and is included in first-choice combination regimens because of its particular ability to kill intracellular persisters, i.e. mycobacteria that are dividing or semidormant, often within cells. Its action is dependent on the activity of intrabacterial pyrazinami-dase which converts pyrazinamide to the active pyrazinoic acid this eirzyme is most effective in an acidic environment such as the interior of cells. It is inactive against Mycobacterium bovis. Pyrazinamide is well absorbed from the gastrointestinal tract and metabolised in the liver, very little imchanged drug... 

Figure 3. Model for the Activity of Coronin 1 in Macrophages. In resting macrophages, coronin 1 (coronin 1 A) is distributed between the cytoplasm as well as the cell cortex. Upon the entry of pathogenic mycobacteria, coronin 1 is recruited and actively retained at the phagosomal membrane, thereby ensuring the activation of calcineurin. Activation of calcineurin results in a block in the fusion of mycobacterial phagosomes with lysosomes. As a consequence, deletion of coronin 1 or inhibiting calcineurin activity results in the induction of phagosome lysosome fusion and mycobacterial killing.

Anes E, KuKnel MP, Bos E cc al. Selected lipids activate phagosome actin assembly and maturation resulting in killing of pathogenic mycobacteria. Nat Cell Biol 2003 5(9) 793-802. 

Freund s adjuvant, consisting of a water-oil emulsion containing killed Mycobacteria in the oil phase and the antigen in the aqueous phase, has been widely used by immunologists Freund has reviewed our knowledge of the mode of action of this type of adjuvant. 

ManLAM and PILAM seem to have opposite effects on the immune response [262,264]. Man-LAM was shown to inhibit macrophage activation, the production of the pro-inflammatory cytokines IL-12 and TNF-o and, M. tuberculosis -induced macrophage apoptosis. PILAM, in contrast, induces the release of pro-inflammatory cytokines. By suppressing the immune response, ManLAM thus promotes survival of pathogenic mycobacteria, while PILAM promotes killing of non-pathogenic mycobacteria. ManLAM and PILAM were also shown to interact with different cell-surface receptors on phagocytic cells [262,264]. 

Complete Freund s adjuvant (CFA) This is composed of an oil-in-water emulsion containing killed mycobacteria, and exhibits a strong adjuvant effect but also severe toxic side-effects [31]. 

Several techniques have been used to produce the reaction, but basically the arthritic syndrome can be elicited by injecting killed mycobacteria in mineral oil into the plantar surface of the foot or intradermally into the tail. From the tenth day onwards the joints of one or all of the feet gradually become inflamed and are painful, particularly when pressure is applied other inflammatory lesions occur in the ears, tail and lungs. These reactions are present in a severe form up to about the thirtieth day, after which they begin to subside . The degree of inflammation can be assessed visually or by measuring the swelling with a micrometer. 

Streptomycin is bactericidal for the tubercle bacillus in vitro. The vast majority of strains of M. tuberculosis are sensitive. M. kansasii is frequently sensitive, but other mycobacteria are only occasionally susceptible. Streptomycin in vivo does not eradicate the tubercle bacillus, probably because the drug does not readily enter living cells and thus cannot kill intracellular microbes. 

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