The <it>Bacillus anthracis </it>cholesterol-dependent cytolysin, Anthrolysin O, kills human neutrophils, monocytes and macrophages
<p>Abstract</p> <p>Background</p> <p><it>Bacillus anthracis </it>is an animal and human pathogen whose virulence is characterized by lethal and edema toxin, as well as a poly-glutamic acid capsule. In addition to these well characterized toxins, <it>B....
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| Format: | Article |
| Language: | English |
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BMC
2006-06-01
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| Series: | BMC Microbiology |
| Online Access: | http://www.biomedcentral.com/1471-2180/6/56 |
| _version_ | 1811315385700450304 |
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| author | Rest Richard F Mosser Elise M |
| author_facet | Rest Richard F Mosser Elise M |
| author_sort | Rest Richard F |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p><it>Bacillus anthracis </it>is an animal and human pathogen whose virulence is characterized by lethal and edema toxin, as well as a poly-glutamic acid capsule. In addition to these well characterized toxins, <it>B. anthracis </it>secretes several proteases and phospholipases, and a newly described toxin of the cholesterol-dependent cytolysin (CDC) family, Anthrolysin O (ALO).</p> <p>Results</p> <p>In the present studies we show that recombinant ALO (rALO) or native ALO, secreted by viable <it>B. anthracis</it>, is lethal to human primary polymorphonuclear leukocytes (PMNs), monocytes, monocyte-derived macrophages (MDMs), lymphocytes, THP-1 monocytic human cell line and ME-180, Detroit 562, and A549 epithelial cells by trypan blue exclusion or lactate dehydrogenase (LDH) release viability assays. ALO cytotoxicity is dose and time dependent and susceptibility to ALO-mediated lysis differs between cell types. In addition, the viability of monocytes and hMDMs was assayed in the presence of vegetative Sterne strains 7702 (ALO+), UT231 (ALO-), and a complemented strain expressing ALO, UT231 (pUTE544), and was dependent upon the expression of ALO. Cytotoxicity of rALO is seen as low as 0.070 nM in the absence of serum. All direct cytotoxic activity is inhibited by the addition of cholesterol or serum concentration as low as 10%.</p> <p>Conclusion</p> <p>The lethality of rALO and native ALO on human monocytes, neutrophils, macrophages and lymphocytes supports the idea that ALO may represent a previously unidentified virulence factor of <it>B. anthracis</it>. The study of other factors produced by <it>B. anthracis</it>, along with the major anthrax toxins, will lead to a better understanding of this bacterium's pathogenesis, as well as provide information for the development of antitoxin vaccines for treating and preventing anthrax.</p> |
| first_indexed | 2024-04-13T11:29:23Z |
| format | Article |
| id | doaj.art-255eb24bccc145738491c8ea54c3e09b |
| institution | Directory Open Access Journal |
| issn | 1471-2180 |
| language | English |
| last_indexed | 2024-04-13T11:29:23Z |
| publishDate | 2006-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Microbiology |
| spelling | doaj.art-255eb24bccc145738491c8ea54c3e09b2022-12-22T02:48:36ZengBMCBMC Microbiology1471-21802006-06-01615610.1186/1471-2180-6-56The <it>Bacillus anthracis </it>cholesterol-dependent cytolysin, Anthrolysin O, kills human neutrophils, monocytes and macrophagesRest Richard FMosser Elise M<p>Abstract</p> <p>Background</p> <p><it>Bacillus anthracis </it>is an animal and human pathogen whose virulence is characterized by lethal and edema toxin, as well as a poly-glutamic acid capsule. In addition to these well characterized toxins, <it>B. anthracis </it>secretes several proteases and phospholipases, and a newly described toxin of the cholesterol-dependent cytolysin (CDC) family, Anthrolysin O (ALO).</p> <p>Results</p> <p>In the present studies we show that recombinant ALO (rALO) or native ALO, secreted by viable <it>B. anthracis</it>, is lethal to human primary polymorphonuclear leukocytes (PMNs), monocytes, monocyte-derived macrophages (MDMs), lymphocytes, THP-1 monocytic human cell line and ME-180, Detroit 562, and A549 epithelial cells by trypan blue exclusion or lactate dehydrogenase (LDH) release viability assays. ALO cytotoxicity is dose and time dependent and susceptibility to ALO-mediated lysis differs between cell types. In addition, the viability of monocytes and hMDMs was assayed in the presence of vegetative Sterne strains 7702 (ALO+), UT231 (ALO-), and a complemented strain expressing ALO, UT231 (pUTE544), and was dependent upon the expression of ALO. Cytotoxicity of rALO is seen as low as 0.070 nM in the absence of serum. All direct cytotoxic activity is inhibited by the addition of cholesterol or serum concentration as low as 10%.</p> <p>Conclusion</p> <p>The lethality of rALO and native ALO on human monocytes, neutrophils, macrophages and lymphocytes supports the idea that ALO may represent a previously unidentified virulence factor of <it>B. anthracis</it>. The study of other factors produced by <it>B. anthracis</it>, along with the major anthrax toxins, will lead to a better understanding of this bacterium's pathogenesis, as well as provide information for the development of antitoxin vaccines for treating and preventing anthrax.</p>http://www.biomedcentral.com/1471-2180/6/56 |
| spellingShingle | Rest Richard F Mosser Elise M The <it>Bacillus anthracis </it>cholesterol-dependent cytolysin, Anthrolysin O, kills human neutrophils, monocytes and macrophages BMC Microbiology |
| title | The <it>Bacillus anthracis </it>cholesterol-dependent cytolysin, Anthrolysin O, kills human neutrophils, monocytes and macrophages |
| title_full | The <it>Bacillus anthracis </it>cholesterol-dependent cytolysin, Anthrolysin O, kills human neutrophils, monocytes and macrophages |
| title_fullStr | The <it>Bacillus anthracis </it>cholesterol-dependent cytolysin, Anthrolysin O, kills human neutrophils, monocytes and macrophages |
| title_full_unstemmed | The <it>Bacillus anthracis </it>cholesterol-dependent cytolysin, Anthrolysin O, kills human neutrophils, monocytes and macrophages |
| title_short | The <it>Bacillus anthracis </it>cholesterol-dependent cytolysin, Anthrolysin O, kills human neutrophils, monocytes and macrophages |
| title_sort | it bacillus anthracis it cholesterol dependent cytolysin anthrolysin o kills human neutrophils monocytes and macrophages |
| url | http://www.biomedcentral.com/1471-2180/6/56 |
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