The mycma_1113 Gene from Mycobacterium abscessus subsp. massiliense is Related to Siderophore Synthesis

Abstract

Iron (Fe) homeostasis control is important for both pathogen and the host. During infection, the host reduces the access of microorganisms to iron, however, studies have shown that virulent pathogens are capable to sequester Fe from host proteins, and establish the infection. M. abscessus subsp. massiliense (Mycma), that is resistant to most drugs used against tuberculosis, was responsible for outbreaks around the world showing increased virulence when compared to other rapidly growing mycobacteria. The goal of this study was to determine whether Mycma produce siderophores and if the mycma_1113 gene expression, a putative homolog of M. tuberculosis mbtB gene located in the mbt gene cluster, is related to the synthesis of these molecules. For that, the effect of different iron concentrations on the growth of Mycma, the expression of mycma_1113 gene, and the production of siderophores was evaluated in vitro and in vivo. It is shown that Mycma produce siderophores under iron deprivation conditions and mycma_1113 gene expression was influenced by iron availability. The mycma_1113 gene expression was also increased after macrophage or in vivo infection indicating that mycobactin synthesis by Mycma could participate in the Fe sequestration from the host during infection. In conclusion, we show that Mycma produces siderophores under iron deprivation conditions and that the mycma_1113 gene is involved in this process, furthermore, this gene expression is induced during infection.

Targeting Siderophore-Mediated Iron Uptake in M. abscessus: A New Strategy to Limit the Virulence of Non-Tuberculous Mycobacteria

“…In light of these considerations, there is a great interest in deciphering the mechanisms of siderophore assembly in Mab , with the goal of targeting selected steps for the development of new drugs. Despite these mechanisms being still poorly characterized in NTM, many research works have been focused on gathering new data, especially in the last years [ 44 , 45 , 46 ]. These preliminary studies seem to support the role of siderophores during Mab infection and suggest a conservation of the enzymes involved in their production.…”