Cumulatively, the results of this work may provide the basis for rational drug design – identifying numerous Mtb proteins, from essential kinases to products involved in metal regulation and cell wall remodeling, all present throughout the course of infection.
Thus, combinations of complementary methods will be required for a comprehensive view of cellular metal regulation.
We provide three recent examples from our laboratory and collaborations in which labile copper contributes to physiology to illustrate the breadth of dynamic transition metal regulation.
The metal homeostasis category contained many genes involved in metal transport or metal regulation assembled from studies reporting mainly their up-regulation in response to - Fe. From the observation that this category was found induced in wild type - vs. + Fe in roots and in leaves we can deduce that indeed the metal homeostasis category was an indicator for Fe deficiency responses.
Measurements in whole-liver tissue from ob/ob mice at an age when they have developed NAFLD/NASH, provide compelling evidence for factitious lowering of copper and all other essential metals by steatosis, and so cannot be used to study hepatic metal regulation in this model.
Our results unravel a complex metal-regulation system involving 3 distinct DMTs coordinately regulated by metal levels, and bear interesting implications on the modulation of the vertebrate DMT activities carried out by NRAMP1 and DMT1 isoforms.
Metallothioneins (MTs) are low-molecular weight, cysteine-rich proteins that bind to the biologically essential metals and perform these metals' homeostatic regulations; absorb the heavy metals and assist with their transportation and extraction.
Additionally, several samples contravene, in at least one heavy metal, current regulations; samples in this condition correspond to 0.5 (n = 2), 13.8 (n = 60), 4.1 (n = 18) and 2.5 % (n = 11) for As, Hg, Pb and Cd, respectively with mercury as the most frequent mineral to surpass, in the majority of cases, current thresholds.
Ultimately these WTRs are applied to land without exceeding metal leachability regulations, discounting concerns over WTR metal content.
Given the distribution of this RNA element, it may constitute a common mode for bacterial metal ion regulation, and its discovery suggests the possibility of additional RNA-based metal sensors in modern and primordial organisms.
