InhA1-Mediated Cleavage of the Metalloprotease NprA Allows Bacillus cereus to Escape From Macrophages
Bacillus cereus is a Gram-positive spore-forming bacterium causing food poisoning and serious opportunistic infections. These infections are characterized by bacterial accumulation in the host despite the induction of inflammation. To circumvent inflammation, bacteria must resist the bactericidal ac...
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Frontiers Media S.A.
2018-05-01
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Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2018.01063/full |
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author | Abbass Haydar Seav-Ly Tran Elisabeth Guillemet Claire Darrigo Stéphane Perchat Didier Lereclus Laurent Coquet Thierry Jouenne Nalini Ramarao |
author_facet | Abbass Haydar Seav-Ly Tran Elisabeth Guillemet Claire Darrigo Stéphane Perchat Didier Lereclus Laurent Coquet Thierry Jouenne Nalini Ramarao |
author_sort | Abbass Haydar |
collection | DOAJ |
description | Bacillus cereus is a Gram-positive spore-forming bacterium causing food poisoning and serious opportunistic infections. These infections are characterized by bacterial accumulation in the host despite the induction of inflammation. To circumvent inflammation, bacteria must resist the bactericidal activity of professional phagocytes, which constitute a first line of host defense against pathogens. Interactions between phagocytic cells and B. cereus are still poorly characterized and the mechanism of resistance to the host immune system is not known yet. We have previously shown that the spores are phagocytosed by macrophages but survive and escape from these cells. The metalloprotease InhA1 is a key effector involved in these processes. inhA1-deficient spores are retained intracellularly, in contrast to the wild type strain spores. NprA is also a B. cereus metalloprotease able to cleave tissue components such as fibronectin, laminin, and collagen. Here, we show that NprA, concomitantly secreted with InhA1 in the B. cereus secretome, is essential to promote bacterial escape from macrophages. We show that InhA1 cleaves NprA at specific sites. This cleavage allows liberation of the mature form of the NprA protein in the supernatant of the wild type strain. This mature form of NprA is actually the principal effector allowing bacterial escape from host macrophages. |
first_indexed | 2024-12-23T03:02:52Z |
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id | doaj.art-0d8386d2bca0490a8f05d6050bf261d1 |
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issn | 1664-302X |
language | English |
last_indexed | 2024-12-23T03:02:52Z |
publishDate | 2018-05-01 |
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series | Frontiers in Microbiology |
spelling | doaj.art-0d8386d2bca0490a8f05d6050bf261d12022-12-21T18:02:22ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2018-05-01910.3389/fmicb.2018.01063356857InhA1-Mediated Cleavage of the Metalloprotease NprA Allows Bacillus cereus to Escape From MacrophagesAbbass Haydar0Seav-Ly Tran1Elisabeth Guillemet2Claire Darrigo3Stéphane Perchat4Didier Lereclus5Laurent Coquet6Thierry Jouenne7Nalini Ramarao8INRA, Micalis Institute, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, FranceINRA, Micalis Institute, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, FranceINRA, Micalis Institute, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, FranceINRA, Micalis Institute, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, FranceINRA, Micalis Institute, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, FranceINRA, Micalis Institute, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, FranceCNRS, UMR 6270, Normandy University, UNIROUEN, Plate-forme PISSARO, Mont-Saint-Aignan, FranceCNRS, UMR 6270, Normandy University, UNIROUEN, Plate-forme PISSARO, Mont-Saint-Aignan, FranceINRA, Micalis Institute, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, FranceBacillus cereus is a Gram-positive spore-forming bacterium causing food poisoning and serious opportunistic infections. These infections are characterized by bacterial accumulation in the host despite the induction of inflammation. To circumvent inflammation, bacteria must resist the bactericidal activity of professional phagocytes, which constitute a first line of host defense against pathogens. Interactions between phagocytic cells and B. cereus are still poorly characterized and the mechanism of resistance to the host immune system is not known yet. We have previously shown that the spores are phagocytosed by macrophages but survive and escape from these cells. The metalloprotease InhA1 is a key effector involved in these processes. inhA1-deficient spores are retained intracellularly, in contrast to the wild type strain spores. NprA is also a B. cereus metalloprotease able to cleave tissue components such as fibronectin, laminin, and collagen. Here, we show that NprA, concomitantly secreted with InhA1 in the B. cereus secretome, is essential to promote bacterial escape from macrophages. We show that InhA1 cleaves NprA at specific sites. This cleavage allows liberation of the mature form of the NprA protein in the supernatant of the wild type strain. This mature form of NprA is actually the principal effector allowing bacterial escape from host macrophages.https://www.frontiersin.org/article/10.3389/fmicb.2018.01063/fullB. cereusprotein interactionmetalloproteasesmacrophagesspores |
spellingShingle | Abbass Haydar Seav-Ly Tran Elisabeth Guillemet Claire Darrigo Stéphane Perchat Didier Lereclus Laurent Coquet Thierry Jouenne Nalini Ramarao InhA1-Mediated Cleavage of the Metalloprotease NprA Allows Bacillus cereus to Escape From Macrophages Frontiers in Microbiology B. cereus protein interaction metalloproteases macrophages spores |
title | InhA1-Mediated Cleavage of the Metalloprotease NprA Allows Bacillus cereus to Escape From Macrophages |
title_full | InhA1-Mediated Cleavage of the Metalloprotease NprA Allows Bacillus cereus to Escape From Macrophages |
title_fullStr | InhA1-Mediated Cleavage of the Metalloprotease NprA Allows Bacillus cereus to Escape From Macrophages |
title_full_unstemmed | InhA1-Mediated Cleavage of the Metalloprotease NprA Allows Bacillus cereus to Escape From Macrophages |
title_short | InhA1-Mediated Cleavage of the Metalloprotease NprA Allows Bacillus cereus to Escape From Macrophages |
title_sort | inha1 mediated cleavage of the metalloprotease npra allows bacillus cereus to escape from macrophages |
topic | B. cereus protein interaction metalloproteases macrophages spores |
url | https://www.frontiersin.org/article/10.3389/fmicb.2018.01063/full |
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