Role for lysosomal enzyme β-hexosaminidase in the control of mycobacteria infection

The pathogenic mycobacteria that cause tuberculosis (TB) and TB-like diseases in humans and animals elude sterilizing immunity by residing within an intracellular niche in host macrophages, where they are protected from microbicidal attack. Recent studies have emphasized microbial mechanisms for eva...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2008-01, Vol.105 (2), p.710-715
Main Authors: Koo, Ingrid Chou, Ohol, Yamini M, Wu, Ping, Morisaki, J. Hiroshi, Cox, Jeffery S, Brown, Eric J
Format: Article
Language:English
Subjects:
Animals
Bacteria
beta-N-Acetylhexosaminidases - chemistry
beta-N-Acetylhexosaminidases - physiology
Biological Sciences
Cell growth
Cell Line
Cells
Dimerization
Drosophila
Drosophila - microbiology
Enzymes
Humans
Infections
Lysosomes
Lysosomes - enzymology
Macrophages
Macrophages - metabolism
Macrophages - microbiology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Microscopy, Phase-Contrast
Mycobacterium
Mycobacterium Infections - enzymology
Mycobacterium Infections - pathology
Mycobacterium marinum
Phagosomes
RNA Interference
Secretion
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Summary:The pathogenic mycobacteria that cause tuberculosis (TB) and TB-like diseases in humans and animals elude sterilizing immunity by residing within an intracellular niche in host macrophages, where they are protected from microbicidal attack. Recent studies have emphasized microbial mechanisms for evasion of host defense; less is known about mycobactericidal mechanisms that remain intact during initial infection. To better understand macrophage mechanisms for restricting mycobacteria growth, we examined Mycobacterium marinum infection of Drosophila S2 cells. Among [almost equal to]1,000 host genes examined by RNAi depletion, the lysosomal enzyme β-hexosaminidase was identified as an important factor in the control of mycobacterial infection. The importance of β-hexosaminidase for restricting mycobacterial growth during mammalian infections was confirmed in macrophages from β-hexosaminidase knockout mice. β-Hexosaminidase was characterized as a peptidoglycan hydrolase that surprisingly exerts its mycobactericidal effect at the macrophage plasma membrane during mycobacteria-induced secretion of lysosomes. Thus, secretion of lysosomal enzymes is a mycobactericidal mechanism that may have a more general role in host defense.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0708110105