The ESX-3 Secretion System Is Necessary for Iron and Zinc Homeostasis in <i>Mycobacterium tuberculosis</i>

<div><p>ESX-3 is one of the five type VII secretion systems encoded by the <i>Mycobacterium tuberculosis</i> genome. We recently showed the essentiality of ESX-3 for <i>M. tuberculosis</i> viability and proposed its involvement in iron and zinc metabolism. In this study we confirmed the role of ESX-3 in iron uptake and its involvement in the adaptation to low zinc environment in <i>M. tuberculosis</i>. Moreover, we unveiled functional differences between the ESX-3 roles in <i>M. tuberculosis</i> and <i>M. smegmatis</i> showing that in the latter ESX-3 is only involved in the adaptation to iron and not to zinc restriction. Finally, we also showed that in <i>M. tuberculosis</i> this secretion system is essential for iron and zinc homeostasis not only in conditions in which the concentrations of these metals are limiting but also in metal sufficient conditions.</p>