Mycobacterium abscessus subsp. massiliense mycma_0076 and mycma_0077 Genes Code for Ferritins That Are Modulated by Iron Concentration

• Published in: Frontiers in microbiology Vol. 9; p. 1072
• Main Authors: Oliveira, Fábio M, Da Costa, Adeliane C, Procopio, Victor O, Garcia, Wanius, Araújo, Juscemácia N, Da Silva, Roosevelt A, Junqueira-Kipnis, Ana Paula, Kipnis, André
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 01.06.2018
• Subjects: ferritin; ferroxidase center; iron homeostasis; iron storage protein; Microbiology; pathogenic; rapid growing mycobacteria; rapid growing mycobacteria; ferritin; iron storage protein; iron homeostasis; pathogenic; ferroxidase center
• ISSN: 1664-302X; 1664-302X
• DOI: 10.3389/fmicb.2018.01072

complex has been characterized in the last decade as part of a cluster of mycobacteria that evolved from an opportunistic to true human pathogen; however, the factors responsible for pathogenicity are still undefined. It appears that the success of mycobacterial infection is intrinsically related with the capacity of the bacteria to regulate intracellular iron levels, mostly using iron storage proteins. This study evaluated two potential subsp. genes involved in iron storage. Unlike other opportunist or pathogenic mycobacteria studied, complex has two genes similar to ferritins from (Rv3841), and in subsp. , those genes are annotated as and . Molecular dynamic analysis of the predicted expressed proteins showed that they have a ferroxidase center. The expressions of and genes were modulated by the iron levels in both cultures as well as infected macrophages. Structural studies using size-exclusion chromatography, circular dichroism spectroscopy and dynamic light scattering showed that r0076 protein has a structure similar to those observed in the ferritin family. The r0076 forms oligomers in solution most likely composed of 24 subunits. Functional studies with recombinant proteins, obtained from heterologous expression of and genes in , showed that both proteins were capable of oxidizing Fe into Fe , demonstrating that these proteins have a functional ferroxidase center. In conclusion, two ferritins proteins were shown, for the first time, to be involved in iron storage in subsp. and their expressions were modulated by the iron levels.