Structural Modeling of Cell Wall Peptidase CwpFM (EntFM) Reveals Distinct Intrinsically Disordered Extensions Specific to Pathogenic <i>Bacillus cereus</i> Strains
The emergence of <i>B. cereus</i> as an opportunistic food-borne pathogen has intensified the need to distinguish strains of public health concern. The heterogeneity of the diseases associated with <i>B. cereus</i> infections emphasizes the versatility of these bacteria strai...
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MDPI AG
2020-09-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/12/9/593 |
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| author | Seav-Ly Tran Delphine Cormontagne Jasmina Vidic Gwenaëlle André-Leroux Nalini Ramarao |
| author_facet | Seav-Ly Tran Delphine Cormontagne Jasmina Vidic Gwenaëlle André-Leroux Nalini Ramarao |
| author_sort | Seav-Ly Tran |
| collection | DOAJ |
| description | The emergence of <i>B. cereus</i> as an opportunistic food-borne pathogen has intensified the need to distinguish strains of public health concern. The heterogeneity of the diseases associated with <i>B. cereus</i> infections emphasizes the versatility of these bacteria strains to colonize their host. Nevertheless, the molecular basis of these differences remains unclear. Several toxins are involved in virulence, particularly in gastrointestinal disorders, but there are currently no biological markers able to differentiate pathogenic from harmless strains. We have previously shown that CwpFM is a cell wall peptidase involved in <i>B. cereus</i> virulence. Here, we report a sequence/structure/function characterization of 39 CwpFM sequences, chosen from a collection of <i>B. cereus</i> with diverse virulence phenotypes, from harmless to highly pathogenic strains. CwpFM is homology-modeled in silico as an exported papain-like endopeptidase, with an N-terminal end composed of three successive bacterial Src Homology 3 domains (SH3b<sub>1–3</sub>) likely to control protein–protein interactions in signaling pathways, and a C-terminal end that contains a catalytic NLPC_P60 domain primed to form a competent active site. We confirmed in vitro that CwpFM is an endopeptidase with a moderate peptidoglycan hydrolase activity. Remarkably, CwpFMs from pathogenic strains harbor a specific stretch of twenty residues intrinsically disordered, inserted between the SH3b<sub>3</sub> and the catalytic NLPC_P60 domain. This strongly suggests this linker as a marker of differentiation between <i>B. cereus</i> strains. We believe that our findings improve our understanding of the pathogenicity of <i>B. cereus</i> while advancing both clinical diagnosis and food safety. |
| first_indexed | 2024-03-10T16:20:22Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-10T16:20:22Z |
| publishDate | 2020-09-01 |
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| series | Toxins |
| spelling | doaj.art-2be741cc78e8490db8c48ee1b798db0a2023-11-20T13:39:54ZengMDPI AGToxins2072-66512020-09-0112959310.3390/toxins12090593Structural Modeling of Cell Wall Peptidase CwpFM (EntFM) Reveals Distinct Intrinsically Disordered Extensions Specific to Pathogenic <i>Bacillus cereus</i> StrainsSeav-Ly Tran0Delphine Cormontagne1Jasmina Vidic2Gwenaëlle André-Leroux3Nalini Ramarao4Micalis Institute, INRAE, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, FranceMicalis Institute, INRAE, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, FranceMicalis Institute, INRAE, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, FranceMaIAGE, INRAE, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, FranceMicalis Institute, INRAE, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, FranceThe emergence of <i>B. cereus</i> as an opportunistic food-borne pathogen has intensified the need to distinguish strains of public health concern. The heterogeneity of the diseases associated with <i>B. cereus</i> infections emphasizes the versatility of these bacteria strains to colonize their host. Nevertheless, the molecular basis of these differences remains unclear. Several toxins are involved in virulence, particularly in gastrointestinal disorders, but there are currently no biological markers able to differentiate pathogenic from harmless strains. We have previously shown that CwpFM is a cell wall peptidase involved in <i>B. cereus</i> virulence. Here, we report a sequence/structure/function characterization of 39 CwpFM sequences, chosen from a collection of <i>B. cereus</i> with diverse virulence phenotypes, from harmless to highly pathogenic strains. CwpFM is homology-modeled in silico as an exported papain-like endopeptidase, with an N-terminal end composed of three successive bacterial Src Homology 3 domains (SH3b<sub>1–3</sub>) likely to control protein–protein interactions in signaling pathways, and a C-terminal end that contains a catalytic NLPC_P60 domain primed to form a competent active site. We confirmed in vitro that CwpFM is an endopeptidase with a moderate peptidoglycan hydrolase activity. Remarkably, CwpFMs from pathogenic strains harbor a specific stretch of twenty residues intrinsically disordered, inserted between the SH3b<sub>3</sub> and the catalytic NLPC_P60 domain. This strongly suggests this linker as a marker of differentiation between <i>B. cereus</i> strains. We believe that our findings improve our understanding of the pathogenicity of <i>B. cereus</i> while advancing both clinical diagnosis and food safety.https://www.mdpi.com/2072-6651/12/9/593<i>Bacillus cereus</i>cell wall peptidasedisordered extensionshomology modeling |
| spellingShingle | Seav-Ly Tran Delphine Cormontagne Jasmina Vidic Gwenaëlle André-Leroux Nalini Ramarao Structural Modeling of Cell Wall Peptidase CwpFM (EntFM) Reveals Distinct Intrinsically Disordered Extensions Specific to Pathogenic <i>Bacillus cereus</i> Strains Toxins <i>Bacillus cereus</i> cell wall peptidase disordered extensions homology modeling |
| title | Structural Modeling of Cell Wall Peptidase CwpFM (EntFM) Reveals Distinct Intrinsically Disordered Extensions Specific to Pathogenic <i>Bacillus cereus</i> Strains |
| title_full | Structural Modeling of Cell Wall Peptidase CwpFM (EntFM) Reveals Distinct Intrinsically Disordered Extensions Specific to Pathogenic <i>Bacillus cereus</i> Strains |
| title_fullStr | Structural Modeling of Cell Wall Peptidase CwpFM (EntFM) Reveals Distinct Intrinsically Disordered Extensions Specific to Pathogenic <i>Bacillus cereus</i> Strains |
| title_full_unstemmed | Structural Modeling of Cell Wall Peptidase CwpFM (EntFM) Reveals Distinct Intrinsically Disordered Extensions Specific to Pathogenic <i>Bacillus cereus</i> Strains |
| title_short | Structural Modeling of Cell Wall Peptidase CwpFM (EntFM) Reveals Distinct Intrinsically Disordered Extensions Specific to Pathogenic <i>Bacillus cereus</i> Strains |
| title_sort | structural modeling of cell wall peptidase cwpfm entfm reveals distinct intrinsically disordered extensions specific to pathogenic i bacillus cereus i strains |
| topic | <i>Bacillus cereus</i> cell wall peptidase disordered extensions homology modeling |
| url | https://www.mdpi.com/2072-6651/12/9/593 |
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