The fbpA/sapM double knock out strain of Mycobacterium tuberculosis is highly attenuated and immunogenic in macrophages.

PloS One
Sankaralingam SaikolappanSubramanian Dhandayuthapani

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 ΔfbpA attenuated mutant underwent limited phagosome maturation, enhanced immunogenicity and was as effective as BCG in protecting mice against TB. To facilitate phagosome maturation of ΔfbpA, we disrupted an additional gene sapM, which encodes for an acid phosphatase. Compared to the wild type Mtb, the ΔfbpAΔsapM (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 lysosomal markers (CD63 and rab7) on DKO phagosomes. An in vitro Antigen 85B peptide presentation assay was used to determine antigen presentation to T cells by APCs infected with DKO or other mycobacterial strains. This revealed that DKO infected APCs showed the strongest ability to p...Continue Reading

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Citations

Oct 31, 2012·Expert Review of Anti-infective Therapy·Rajesh JayachandranJean Pieters
Sep 15, 2015·Expert Review of Vaccines·Tony W NgSteven A Porcelli
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Apr 8, 2021·Microbiology·Leah Isobella Rankine-WilsonYossef Av-Gay

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Datasets Mentioned

BETA
GM-CSF

Methods Mentioned

BETA
PCR
ELISA
PMA
Assay

Software Mentioned

Metaview
Elispot

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