Mycobacterium abscessus (M. abs) is an emerging pathogen causing lung infections in cystic fibrosis patients. Although the environmental reservoir of M. abs is currently unknown, M. abs possesses a gene pool dedicated to a life at the water-plant interface. Amoebae are an integral part of this environment, especially those of the genus Acanthamoeba. We recently demonstrated that coculture of M. abs within amoebae confers to this mycobacterial strains an increased virulence, observed with our aerosol mouse model of infection (Bakala N’Goma et al., 2015). A complete RNAseq experiment should help us to better understand the underlying mechanisms, by comparing the messenger RNAs produce by M. abs in contact with amoeba or not. We think indeed that the increased infectivity of M. abs in mice is linked to the accumulation of a “virulence” capital acquired during its intra-amoeba life.