the fbpasapm double knock out strain of mycobacterium tuberculosis is highly attenuated and immunogenic in macrophagesfbpasapm双敲除株结核分枝杆菌高度减毒和巨噬细胞的免疫原性.pdf

The fbpA/sapM Double Knock Out Strain of Mycobacterium tuberculosis Is Highly Attenuated and Immunogenic in Macrophages 1 2 1 2 2 Sankaralingam Saikolappan , Jaymie Estrella , Smitha J. Sasindran , Arshad Khan , Lisa Y. Armitige , 2 1 Chinnaswamy Jagannath *, Subramanian Dhandayuthapani * 1 Regional Academic Health Center and Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, Edinburg, Texas, United States of America, 2 Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at Houston, Houston, Texas, United States of America Abstract Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is the leading cause of death due to bacterial infections in mankind, and BCG, an attenuated strain of Mycobacterium bovis, is an approved vaccine. BCG sequesters in immature phagosomes of antigen presenting cells (APCs), which do not fuse with lysosomes, leading to decreased antigen processing and reduced Th1 responses. However, an Mtb derived DfbpA attenuated mutant underwent limited phagosome maturation, enhanced immunogenicity and was as effective as BCG in protecting mice against TB. To facilitate phagosome maturation of DfbpA, we disrupted an additional gene sapM, which encodes for an acid phosphatase. Compared to the wild type Mtb, the DfbpADsapM (double knock out; DKO) strain was attenuated for growth in mouse macrophages and PMA activated human THP1 macrophages. Attenuation correlated with increased oxidants in macrophages in response to DKO infection and enhanced labeling of