ABSTRACT
SecA2 is an ATPase present in some pathogenic Gram-positive bacteria, is required for translocation of a limited set of proteins across the cytosolic membrane, and plays an important role in virulence in several bacteria, including mycobacteria that cause diseases such as tuberculosis and leprosy. However, the mechanisms by which SecA2 affects virulence are incompletely understood. To investigate whether SecA2 modulates host immune responses in vivo, we studied Mycobacterium marinum infection in two different hosts: an established zebrafish model and a recently described mouse model. Here we show that M. marinum ΔsecA2 was attenuated for virulence in both host species and SecA2 was needed for normal granuloma numbers and for optimal tumor necrosis factor alpha response in both zebrafish and mice. M. marinum ΔsecA2 was more sensitive to SDS and had unique protrusions from its cell envelope when examined by cryo-electron tomography, suggesting that SecA2 is important for bacterial cell wall integrity. These results provide evidence that SecA2 induces granulomas and is required for bacterial modulation of the host response because it affects the mycobacterial cell envelope.
Subject(s)
Adenosine Triphosphatases/metabolism , Bacterial Proteins/metabolism , Granuloma/microbiology , Membrane Transport Proteins/metabolism , Mycobacterium Infections, Nontuberculous/microbiology , Mycobacterium marinum/metabolism , Tumor Necrosis Factor-alpha/metabolism , Adenosine Triphosphatases/genetics , Animals , Bacterial Proteins/genetics , Cells, Cultured , Female , Humans , Inflammation/metabolism , Macrophages , Membrane Transport Proteins/genetics , Mice , Mice, Inbred C57BL , Mycobacterium Infections, Nontuberculous/immunology , Mycobacterium Infections, Nontuberculous/metabolism , Mycobacterium marinum/genetics , Mycobacterium marinum/pathogenicity , Reverse Transcriptase Polymerase Chain Reaction , Tumor Necrosis Factor-alpha/genetics , Virulence , ZebrafishABSTRACT
As improvements in antiretroviral therapy continue to extend lifespans and enhance quality of life, more people living with HIV are hoping and planning to become parents. Roughly three-quarters of HIV positive people in the United States are of reproductive age, and multiple recent studies have found that an HIV diagnosis does little to dampen the desire to have a child.
