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

Koo, Ingrid Chou; Ohol, Yamini M.; Wu, Ping; Morisaki, J. Hiroshi; Cox, Jeffery S.; Brown, Eric J.

doi:10.1073/pnas.0708110105

Cited by 77 publications

(75 citation statements)

References 35 publications

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“…The effect of FUCA2 on H. pylori was examined by 2 studies: RNA interference-mediated depletion of FUCA2 and treatment of H. pylori-infected cells with FNJ, both of which effectively prevented adherence of H. pylori to host cells The aforementioned host defense mechanism to exploit ␣-Lfucosidase for removal of L-fucose residues was not unexpected. ␤-Hexosaminidase, for instance, was characterized as a peptidoglycan hydrolase that exerts its mycobactericidal effect at the macrophage plasma membrane when secretion from host lysosomes is induced by mycobacteria (32). Moreover, our findings indicate that H. pylori adhesion to host cells is related to the presence of FUCA2.…”

Section: Discussionmentioning

confidence: 48%

Role for α- l -fucosidase in the control of Helicobacter pylori -infected gastric cancer cells

Liu

Huang

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Infecting about one-half of the global human population, Helicobacter pylori is well established as the primary cause of gastritis, duodenal ulcer, and gastric cancer. Currently there is no clear information regarding if and how host cells interact with H. pylori, and if such interactions are dependent on the type of gastric disease. Using fluorescently labeled fucose-containing glycoconjugates, we provide evidence observing both the uptake of L-fucose from gastric cancer cells to H. pylori and that human ␣-L-fucosidase 2 (FUCA2) is secreted only under coculture conditions (i.e., host cells infected with H. pylori). Upon depletion of FUCA2 by RNA interference and detection of translocated CagA (a virulence factor of H. pylori) in host cells, FUCA2 was found to be essential for H. pylori adhesion, in particular to the gastric cancer-and duodenal ulcer-specific strains. Additionally FUCA2 was shown to significantly enhance the expression of Lewis x antigen in H. pylori, which is critical for bacterial cell adhesion in the pathogenesis and defense strategy to escape host surveillance. These findings not only demonstrate an important connection between FUCA2 and the adhesion, growth, and pathogenicity of H. pylori, but also support the idea that FUCA2 is a potential target for clinical diagnosis and therapeutic intervention of H. pylori-related diseases.

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Section: Discussionmentioning

confidence: 48%

Role for α- l -fucosidase in the control of Helicobacter pylori -infected gastric cancer cells

Liu

Huang

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…Striker et al (45) suggested that degradation of gonococcal PGN is mediated by b-hexosaminidase released from neutrophil granules. Additionally, Koo et al (46) reported that b-hexosaminidase exerts mycobactericidal activity in the lysosome of macrophages. Bacterial cell wall PGN is a polymer composed of sugars and amino acids.…”

Section: Discussionmentioning

confidence: 99%

Does β-Hexosaminidase Function Only as a Degranulation Indicator in Mast Cells? The Primary Role of β-Hexosaminidase in Mast Cell Granules

Fukuishi

Murakami

Ohno

et al. 2014

The Journal of Immunology

100

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β-Hexosaminidase, which is generally present in the lysosome, is essential for glycoprotein metabolism in the maintenance of cell homeostasis. In mast cells (MCs), large amounts of β-hexosaminidase are present in the granules as opposed to the lysosome, and the biological role of MC β-hexosaminidase has yet to be fully elucidated. Therefore, we investigated the biological role of β-hexosaminidase in MC granules. Bone marrow-derived MCs from C57BL/6 (BL/6-BMMC) or β-hexosaminidase gene–deficient (hexb−/−-BMMC) mice were transplanted into MC-deficient (WBB6F1/J-KitW/KitW-v [W/Wv]) mice to generate MC-reconstituted models. In asthma model experiments, no differences were observed in the symptoms of BL/6, W/Wv, BL/6-BMMC–reconstituted W/Wv, or hexb−/−-BMMC–reconstituted W/Wv mice. In Staphylococcus epidermidis experimental infection model experiments, the severity of symptoms and frequency of death were markedly higher in W/Wv and hexb−/−-BMMC–reconstituted W/Wv mice than in BL/6 and BL/6-BMMC–reconstituted W/Wv mice. The growth of S. epidermidis in an in vitro study was clearly inhibited by addition of BL/6-BMMC lysate, but not by addition of hexb−/−-BMMC lysate. Moreover, suppression of bacterial proliferation was completely recovered when bacteria were incubated with hexb−/−-BMMC lysate plus β-hexosaminidase. Transmission electron microscopy indicated that the cell wall of S. epidermidis was heavily degraded following coincubation of bacteria with BL/6-BMMC lysate, but not following coincubation with hexb−/−-BMMC lysate. These findings strongly suggest that MC granule β-hexosaminidase is crucial for defense against bacterial invasion, but is not involved in the allergic response. Our results also suggest that the bactericidal mechanism of β-hexosaminidase involves degradation of bacterial cell wall peptidoglycan.

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“…In particular, it has been successfully manipulated for the identification of genes involved in host-pathogen interactions. These pathogens include Listeria monocytogenes (1,2), Chlamydia trachomatis (20), Mycobacterium marinum (1,18,30,48), Francisella tularensis (51,64), and the protozoan parasite Plasmodium gallinaceum (8,53).…”

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confidence: 99%

Identification of Critical Host Mitochondrion-Associated Genes during Ehrlichia chaffeensis Infections

et al. 2012

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bEhrlichia chaffeensis is an obligate intracellular bacterium that causes human monocytic ehrlichiosis (HME). To determine what host components are important for bacterial replication, we performed microarray analysis on Drosophila melanogaster S2 cells by comparing host gene transcript levels between permissive and nonpermissive conditions for E. chaffeensis growth. Five-hundred twenty-seven genes had increased transcript levels unique to permissive growth conditions 24 h postinfection. We screened adult flies that were mutants for several of the "permissive" genes for the ability to support Ehrlichia replication. Three additional D. melanogaster fly lines with putative mutations in pyrimidine metabolism were also tested. Ten fly lines carrying mutations in the genes CG6479, separation anxiety, chitinase 11, CG6364 (Uck2), CG6543 (Echs1), withered (whd), CG15881 (Ccdc58), CG14806 (Apop1), CG11875 (Nup37), and dumpy (dp) had increased resistance to infection with Ehrlichia. Analysis of RNA by quantitative real-time reverse transcription-PCR (qRT-PCR) confirmed that the bacterial load was decreased in these mutant flies compared to wild-type infected control flies. Seven of these genes (san, Cht11, Uck2, Echs1, whd, Ccdc58, and Apop1) encoded proteins that had mitochondrial functions or could be associated with proteins with mitochondrial functions. Treatment of THP-1 cells with double-stranded RNA to silence the human UCK2 gene indicates that the disruption of the uridine-cytidine kinase affects E. chaffeensis replication in human macrophages. Experiments with cyclopentenyl cytosine (CPEC), a CTP synthetase inhibitor and cytosine, suggest that the nucleotide salvage pathway is essential for E. chaffeensis replication and that it may be important for the provision of CTP, uridine, and cytidine nucleotides. Ehrlichia chaffeensis is the causative agent of human monocytic ehrlichiosis (HME). There were 1,429 cases of HME in 2010 and 2011 (14). This represents a significant increase in the incidence of the disease since 2003 and qualifies HME as an emerging infectious disease (25). In addition to being reported in the United States, HME has also been documented in Africa, Europe, China, and Brazil (9,16,42,67). E. chaffeensis is an obligate intracellular bacterium. However, little is known about the parasitized-host requirements for bacterial replication.Drosophila melanogaster has been used to study a variety of intracellular pathogens. In particular, it has been successfully manipulated for the identification of genes involved in host-pathogen interactions. These pathogens include Listeria monocytogenes (1, 2), Chlamydia trachomatis (20), Mycobacterium marinum (1, 18, 30, 48), Francisella tularensis (51, 64), and the protozoan parasite Plasmodium gallinaceum (8,53).We previously demonstrated that E. chaffeensis is capable of infecting, completing its life cycle, and maintaining its pathogenicity in both Drosophila S2 cells (39) and adult flies (40). We have also identified growth conditions that were nonpermissiv...

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

Cited by 77 publications

References 35 publications

Role for α- l -fucosidase in the control of Helicobacter pylori -infected gastric cancer cells

Role for α- l -fucosidase in the control of Helicobacter pylori -infected gastric cancer cells

Does β-Hexosaminidase Function Only as a Degranulation Indicator in Mast Cells? The Primary Role of β-Hexosaminidase in Mast Cell Granules

Identification of Critical Host Mitochondrion-Associated Genes during Ehrlichia chaffeensis Infections

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