The extracellular innate-immune effector HMGB1 limits pathogenic bacterial biofilm proliferation
Herein, we describe an extracellular function of the vertebrate high-mobility group box 1 protein (HMGB1) in the proliferation of bacterial biofilms. Within host cells, HMGB1 functions as a DNA architectural protein, similar to the ubiquitous DNABII family of bacterial proteins; despite that, these proteins share no amino acid sequence identity. Extracellularly, HMGB1 induces a proinflammatory immune response, whereas the DNABII proteins stabilize the extracellular DNA-dependent matrix that maintains bacterial biofilms. We showed that when both proteins converged on extracellular DNA within bacterial biofilms, HMGB1, unlike the DNABII proteins, disrupted biofilms both in vitro (including the high-priority ESKAPEE pathogens) and in vivo in 2 distinct animal models, albeit with induction of a strong inflammatory response that we attenuated by a single engineered amino acid change. We propose a model where extracellular HMGB1 balances the degree of induced inflammation and biofilm containment without excessive release of biofilm-resident bacteria.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:131 |
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| Enthalten in: |
The Journal of clinical investigation - 131(2021), 16 vom: 16. Aug. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Devaraj, Aishwarya [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 08.11.2021 Date Revised 17.11.2021 published: Print Citation Status MEDLINE |
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| doi: |
10.1172/JCI140527 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Devaraj, Aishwarya |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The extracellular innate-immune effector HMGB1 limits pathogenic bacterial biofilm proliferation |
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| 500 | |a Date Completed 08.11.2021 | ||
| 500 | |a Date Revised 17.11.2021 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Herein, we describe an extracellular function of the vertebrate high-mobility group box 1 protein (HMGB1) in the proliferation of bacterial biofilms. Within host cells, HMGB1 functions as a DNA architectural protein, similar to the ubiquitous DNABII family of bacterial proteins; despite that, these proteins share no amino acid sequence identity. Extracellularly, HMGB1 induces a proinflammatory immune response, whereas the DNABII proteins stabilize the extracellular DNA-dependent matrix that maintains bacterial biofilms. We showed that when both proteins converged on extracellular DNA within bacterial biofilms, HMGB1, unlike the DNABII proteins, disrupted biofilms both in vitro (including the high-priority ESKAPEE pathogens) and in vivo in 2 distinct animal models, albeit with induction of a strong inflammatory response that we attenuated by a single engineered amino acid change. We propose a model where extracellular HMGB1 balances the degree of induced inflammation and biofilm containment without excessive release of biofilm-resident bacteria | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Bacterial infections | |
| 650 | 4 | |a Drug therapy | |
| 650 | 4 | |a Immunology | |
| 650 | 4 | |a Immunotherapy | |
| 650 | 4 | |a Infectious disease | |
| 650 | 7 | |a Bacterial Proteins |2 NLM | |
| 650 | 7 | |a DNA, Bacterial |2 NLM | |
| 650 | 7 | |a HMGB1 Protein |2 NLM | |
| 700 | 1 | |a Novotny, Laura A |e verfasserin |4 aut | |
| 700 | 1 | |a Robledo-Avila, Frank H |e verfasserin |4 aut | |
| 700 | 1 | |a Buzzo, John R |e verfasserin |4 aut | |
| 700 | 1 | |a Mashburn-Warren, Lauren |e verfasserin |4 aut | |
| 700 | 1 | |a Jurcisek, Joseph A |e verfasserin |4 aut | |
| 700 | 1 | |a Tjokro, Natalia O |e verfasserin |4 aut | |
| 700 | 1 | |a Partida-Sanchez, Santiago |e verfasserin |4 aut | |
| 700 | 1 | |a Bakaletz, Lauren O |e verfasserin |4 aut | |
| 700 | 1 | |a Goodman, Steven D |e verfasserin |4 aut | |
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