Indeed, M. tuberculosis, M. bovis and/or M. marinum mutants lacking an intact ESX-1 secretion system or its substrates have been shown to be attenuated in cultured macrophages and animal models of infection, thereby exhibiting defects in cell to cell spread, altered cytokine profiles [23], [26], [40]–[42] or phagosome maturation arrest [43]. Here, ESX1 is linked to infection.