FtsZ Interactions and Biomolecular Condensates as Potential Targets for New Antibiotics

FtsZ is an essential and central protein for cell division in most bacteria. Because of its ability to organize into dynamic polymers at the cell membrane and recruit other protein partners to form a “divisome”, FtsZ is a leading target in the quest for new antibacterial compounds. Strategies to pot...

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Main Authors: Silvia Zorrilla, Begoña Monterroso, Miguel-Ángel Robles-Ramos, William Margolin, Germán Rivas
Format: Article
Language:English
Published: MDPI AG 2021-03-01
Series:Antibiotics
Subjects:
Online Access:https://www.mdpi.com/2079-6382/10/3/254
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author Silvia Zorrilla
Begoña Monterroso
Miguel-Ángel Robles-Ramos
William Margolin
Germán Rivas
author_facet Silvia Zorrilla
Begoña Monterroso
Miguel-Ángel Robles-Ramos
William Margolin
Germán Rivas
author_sort Silvia Zorrilla
collection DOAJ
description FtsZ is an essential and central protein for cell division in most bacteria. Because of its ability to organize into dynamic polymers at the cell membrane and recruit other protein partners to form a “divisome”, FtsZ is a leading target in the quest for new antibacterial compounds. Strategies to potentially arrest the essential and tightly regulated cell division process include perturbing FtsZ’s ability to interact with itself and other divisome proteins. Here, we discuss the available methodologies to screen for and characterize those interactions. In addition to assays that measure protein-ligand interactions in solution, we also discuss the use of minimal membrane systems and cell-like compartments to better approximate the native bacterial cell environment and hence provide a more accurate assessment of a candidate compound’s potential in vivo effect. We particularly focus on ways to measure and inhibit under-explored interactions between FtsZ and partner proteins. Finally, we discuss recent evidence that FtsZ forms biomolecular condensates in vitro, and the potential implications of these assemblies in bacterial resistance to antibiotic treatment.
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spelling doaj.art-615b018d76f74ef4a25db48fc7196cf12023-12-03T12:25:29ZengMDPI AGAntibiotics2079-63822021-03-0110325410.3390/antibiotics10030254FtsZ Interactions and Biomolecular Condensates as Potential Targets for New AntibioticsSilvia Zorrilla0Begoña Monterroso1Miguel-Ángel Robles-Ramos2William Margolin3Germán Rivas4Centro de Investigaciones Biológicas Margarita Salas, Consejo Superior de Investigaciones Científicas (CSIC), 28040 Madrid, SpainCentro de Investigaciones Biológicas Margarita Salas, Consejo Superior de Investigaciones Científicas (CSIC), 28040 Madrid, SpainCentro de Investigaciones Biológicas Margarita Salas, Consejo Superior de Investigaciones Científicas (CSIC), 28040 Madrid, SpainDepartment of Microbiology and Molecular Genetics, McGovern Medical School, University of Texas, Houston, TX 77030, USACentro de Investigaciones Biológicas Margarita Salas, Consejo Superior de Investigaciones Científicas (CSIC), 28040 Madrid, SpainFtsZ is an essential and central protein for cell division in most bacteria. Because of its ability to organize into dynamic polymers at the cell membrane and recruit other protein partners to form a “divisome”, FtsZ is a leading target in the quest for new antibacterial compounds. Strategies to potentially arrest the essential and tightly regulated cell division process include perturbing FtsZ’s ability to interact with itself and other divisome proteins. Here, we discuss the available methodologies to screen for and characterize those interactions. In addition to assays that measure protein-ligand interactions in solution, we also discuss the use of minimal membrane systems and cell-like compartments to better approximate the native bacterial cell environment and hence provide a more accurate assessment of a candidate compound’s potential in vivo effect. We particularly focus on ways to measure and inhibit under-explored interactions between FtsZ and partner proteins. Finally, we discuss recent evidence that FtsZ forms biomolecular condensates in vitro, and the potential implications of these assemblies in bacterial resistance to antibiotic treatment.https://www.mdpi.com/2079-6382/10/3/254bacterial cell divisionFtsZ association statesprotein interactionsbiomolecular condensatesmacromolecular crowdingphase separation
spellingShingle Silvia Zorrilla
Begoña Monterroso
Miguel-Ángel Robles-Ramos
William Margolin
Germán Rivas
FtsZ Interactions and Biomolecular Condensates as Potential Targets for New Antibiotics
Antibiotics
bacterial cell division
FtsZ association states
protein interactions
biomolecular condensates
macromolecular crowding
phase separation
title FtsZ Interactions and Biomolecular Condensates as Potential Targets for New Antibiotics
title_full FtsZ Interactions and Biomolecular Condensates as Potential Targets for New Antibiotics
title_fullStr FtsZ Interactions and Biomolecular Condensates as Potential Targets for New Antibiotics
title_full_unstemmed FtsZ Interactions and Biomolecular Condensates as Potential Targets for New Antibiotics
title_short FtsZ Interactions and Biomolecular Condensates as Potential Targets for New Antibiotics
title_sort ftsz interactions and biomolecular condensates as potential targets for new antibiotics
topic bacterial cell division
FtsZ association states
protein interactions
biomolecular condensates
macromolecular crowding
phase separation
url https://www.mdpi.com/2079-6382/10/3/254
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AT miguelangelroblesramos ftszinteractionsandbiomolecularcondensatesaspotentialtargetsfornewantibiotics
AT williammargolin ftszinteractionsandbiomolecularcondensatesaspotentialtargetsfornewantibiotics
AT germanrivas ftszinteractionsandbiomolecularcondensatesaspotentialtargetsfornewantibiotics