scholarly journals Rifampin Induces Hydroxyl Radical Formation in Mycobacterium tuberculosis

2014 ◽  
Vol 58 (12) ◽  
pp. 7527-7533 ◽  
Author(s):  
Giovanni Piccaro ◽  
Donatella Pietraforte ◽  
Federico Giannoni ◽  
Alessandro Mustazzolu ◽  
Lanfranco Fattorini

ABSTRACTThe antituberculosis (anti-TB) drug rifampin (RIF) binds to the beta subunit of the RNA polymerase (RpoB) ofMycobacterium tuberculosis, but the bactericidal responses triggered after target interaction are not known. To evaluate whether RIF induced an oxidative burst, lysates of RIF-treatedM. tuberculosiswere tested for determination of reactive oxygen species (ROS) by the electron paramagnetic resonance (EPR) technique using 1-hydroxy-3-carboxy-pyrrolidine (CPH) and 5,5-dimethyl-1-pyrrolidine-N-oxide (DMPO) as spin traps.M. tuberculosiskilling by RIF stimulated an increase in the rate of formation of the CPH radical (CP·). Lysate pretreatment with the O2·−and ·OH scavengers superoxide dismutase (SOD) and thiourea (THIO), respectively, or with the metal chelator diethylene triamine pentaacetic acid (DTPA) inhibited CP· formation, arguing in favor of a metal-catalyzed ROS response. Formation of CP· did not increase following treatment of RIF-resistant strains with RIF, indicating that the ROS were induced after RpoB binding. To identify the ROS formed, lysates of RIF-treated bacilli were incubated with DMPO, a spin trap specific for ·OH and O2·−, with or without pretreatment with SOD, catalase, THIO, or DTPA. Superoxide dismutase, catalase, and THIO decreased formation of the DMPO-OH adduct, and SOD plus DTPA completely suppressed it, suggesting that RIF activated metal-dependent O2·−-mediated mechanisms producing ·OH inside tubercle bacilli. The finding that the metal chelator DTPA reduced the bactericidal activity of RIF supported the possibility that ·OH was generated through these mechanisms and that it participated at least in part inM. tuberculosiskilling by the drug.

1973 ◽  
Vol 51 (10) ◽  
pp. 1530-1534 ◽  
Author(s):  
J. B. Farmer ◽  
F. G. Herring ◽  
R. L. Tapping

The stoichiometry of the adducts formed between copper(II) bis(diethyldithiocarbamate) and pyridine in benzene, toluene, and chloroform and between 3-picoline, 4-picoline, and 3,4-lutidine in benzene are shown to be 1:1. The method employed is that of Scatchard using electron paramagnetic resonance studies.


Type I (a) diamonds contain high concentrations of nitrogen, almost all of which is in an aggregated form. The two main aggregates are recognized by characteristic absorption features in the infrared region of the spectrum. These are called A and B features; usually a peak designated B' is also present. When such diamonds were heated at 1960 °C and above under a stabilizing pressure of 85kbar (8.5 GPa) the nitrogen aggregates partially dissociated, producing single substitutional atoms which were identified by electron paramagnetic resonance (e.p.r.) measurements. Experiments with selected diamonds, showing wide variations in their characteristic infrared absorption, determined the relative stability of the A and B centres. Optical measurements led to the determination of a general relation between the strengths of the A, B and B' features. The experimental observations suggest a scheme for the occurrence of type I (a) diamonds containing nitrogen atoms which have aggregated into A centres; type I (b) diamonds can also be included in this scheme.


2012 ◽  
Vol 79 (2) ◽  
pp. 722-724 ◽  
Author(s):  
Yuan Yan ◽  
Joy G. Waite-Cusic ◽  
Periannan Kuppusamy ◽  
Ahmed E. Yousef

ABSTRACTIntracellular free iron ofEscherichia coliwas determined by whole-cell electron paramagnetic resonance spectrometry. Ultrahigh pressure (UHP) increased both intracellular free iron and cell lethality in a pressure-dose-dependent manner. The iron chelator 2,2′-dipyridyl protected cells against UHP treatments. A mutation that produced iron overload conditions sensitizedE. colito UHP treatment.


Sign in / Sign up

Export Citation Format

Share Document