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Abstract: Tuberculosis is a major health problem in Portugal. To begin characterizing the population structure of Mycobacterium tuberculosis, spoligotyping was used for the systematic typing, through consecutive sampling, of patient isolates from the Amadora-Sintra area of Greater Lisbon. Distribution amongst major spoligotype families, including the Latin American Mediterranean (LAM), T, Haarlem and Beijing, was compared to that of the international spoligotype database SpolDB4 and to the European countries of traditional Portuguese immigration represented in SpolDB4. Spoligotypes from 665 isolates were analyzed and 97 shared international types (SITs) identified. In SpolDB4 Portugal is represented by part of the spoligotypes from this study explaining the reduced number of unidentified patterns. The importance of the LAM family, and especially of LAM1 and LAM9 sub-families that alone represented 38% of all the isolates in this study as compared to 8% relative to the European sub group, led us to believe that at least in this respect the population structure was closer to that of Africa and South America than to Europe. Spoligotypes characteristic of Portugal or Portuguese related settings were identified. These included SIT244 a T1 sub-family predominant in Portugal and Bangladesh, SIT64 a LAM 6 sub-family common to Portugal and Brazil, and SIT1106 a LAM 9 sub-family. These studies were the first in Portugal stressing the importance of monitoring the population structure of M. tuberculosis isolates, an important step towards gaining an understanding of tuberculosis and the dynamics of this disease. [Copyright &y& Elsevier]

Abstract: In mycobacteria, the study of inhibition by metal ions has been limited by the absence of suitable molecular vectors. Recently, we reported on the inhibitory activity of a family of chelators, macrocyclic compounds (MCC), against Mycobacterium tuberculosis. In this study equimolar concentrations of the free cations vanadium(IV), arsenic(III), iron(III), indium(III) and bismuth(III), and as 1:1 complexes with the MCC 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetra-acetic acid (TETA) were tested in vitro against M. tuberculosis using the Bactec™ 460 TB radiometric technology (Becton-Dickinson, MD, USA). Radiometric inhibition above 80% was obtained with free indium(III) and bismuth(III), and ranged from 80% to 99%, with the complexes of TETA with vanadium(IV), bismuth(III) and indium(III), in the order of increasing activity. The highest radiometric inhibition levels were obtained with the [In(TETA)]− complex, which caused drops of up to 4log units in cellular viability. The minimal inhibitory concentration of this compound was evaluated at 3μM. [Copyright &y& Elsevier]