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Mycobacterium abscessus is an emerging pathogenic mycobacterium involved in pulmonary and mucocutaneous infections, presenting a serious threat for patients with cystic fibrosis (CF). The lack of an efficient treatment regimen and the emergence of multidrug resistance in clinical isolates require the development of new therapeutic strategies against this pathogen. Reverse genetics has revealed genes that are present inM. abscessus but absent from saprophytic mycobacteria and that are potentially involved in pathogenicity. Among them,MAB_3593 encodes MgtC, a known virulence factor involved in intramacrophage survival and adaptation to Mg2+ deprivation in several major bacterial pathogens. Here, we demonstrated a strong induction ofM. abscessus MgtC at both the transcriptional and translational levels when bacteria reside inside macrophages or upon Mg2+ deprivation. Moreover, we showed thatM. abscessus MgtC was recognized by sera fromM. abscessus -infected CF patients. The intramacrophage growth (J774 or THP1 cells) of aM. abscessus knockoutmgtC mutant was, however, not significantly impeded. Importantly, our results indicated that inhibition of MgtCin vivo through immunization withM. abscessus mgtC DNA, formulated with a tetrafunctional amphiphilic block copolymer, exerted a protective effect against an aerosolizedM. abscessus challenge in CF (ΔF508 FVB) mice. The formulated DNA immunization was likely associated with the production of specific MgtC antibodies, which may stimulate a protective effect by counteracting MgtC activity duringM. abscessus infection. These results emphasize the importance ofM. abscessus MgtCin vivo and provide a basis for the development of novel therapeutic tools against pulmonaryM. abscessus infections in CF patients.

MgtC as a Host-Induced Factor and Vaccine Candidate against Mycobacterium abscessus Infection