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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Main Authors: Abbass Haydar, Seav-Ly Tran, Elisabeth Guillemet, Claire Darrigo, Stéphane Perchat, Didier Lereclus, Laurent Coquet, Thierry Jouenne, Nalini Ramarao
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-05-01
Series:Frontiers in Microbiology
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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.
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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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