scholarly journals The cell cycle regulator GpsB functions as cytosolic adaptor for multiple cell wall enzymes

2018 ◽  
Author(s):  
Robert M. Cleverley ◽  
Zoe J. Rutter ◽  
Jeanine Rismondo ◽  
Federico Corona ◽  
Ho-Ching Tiffany Tsui ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Wall ◽  
Bacterial Cell ◽  
Pathogenic Bacteria ◽  
Structural Features ◽  
Subcellular Localisation ◽  
Dependent Manner ◽  
Cell Wall Synthesis ◽  
Starting Point ◽  
Bacterial Cell Cycle

AbstractBacterial growth and cell division requires precise spatiotemporal regulation of the synthesis and remodelling of the peptidoglycan layer that surrounds the cytoplasmic membrane. GpsB is a cytosolic protein that affects cell wall synthesis by binding to the cytoplasmic mini-domains of peptidoglycan synthases to ensure their correct subcellular localisation. Here we have discovered critical structural features for the interaction of GpsB with peptidoglycan synthases from three different bacteria and demonstrated their importance for cell wall growth and viability. We have used these structural motifs to predict and confirm novel partners of GpsB in Bacillus subtilis, illuminating the role of this key regulator of peptidoglycan synthesis. GpsB thus functions as an adaptor, to mediate the interaction between membrane proteins, scaffolding proteins, signalling proteins and enzymes to generate larger protein complexes at specific sites in a bacterial cell cycle-dependent manner. Given the importance of GpsB in pathogenic bacteria, this study has not only revealed mechanistic details of how cell wall synthesis is co-ordinated with the bacterial cell cycle but could also represent a starting point for the design of much needed new antibiotics.

scholarly journals The chaperonin GroESL facilitates Caulobacter crescentus cell division by supporting the function of the actin homologue FtsA

2020 ◽  
Author(s):  
Kristen Schroeder ◽  
Kristina Heinrich ◽  
Ines Neuwirth ◽  
Kristina Jonas
Keyword(s):  
Cell Cycle ◽  
Cell Wall ◽  
Cell Division ◽  
Bacterial Cell ◽  
Antimicrobial Agents ◽  
Caulobacter Crescentus ◽  
Bacterial Cell Division ◽  
Growing Cell ◽  
Bacterial Cell Cycle

AbstractThe highly conserved chaperonin GroESL performs a crucial role in protein folding, however the essential cellular pathways that rely on this chaperone are underexplored. Loss of GroESL leads to severe septation defects in diverse bacteria, suggesting the folding function of GroESL may be integrated with the bacterial cell cycle at the point of cell division. Here, we describe new connections between GroESL and the bacterial cell cycle, using the model organism Caulobacter crescentus. Using a proteomics approach, we identify candidate GroESL client proteins that become insoluble or are degraded specifically when GroESL folding is insufficient, revealing several essential proteins that participate in cell division and peptidoglycan biosynthesis. We demonstrate that other cell cycle events such as DNA replication and chromosome segregation are able to continue when GroESL folding is insufficient, and find that deficiency of the bacterial actin homologue FtsA function mediates the GroESL-dependent block in cell division. Our data suggest that a GroESL-FtsA interaction is required to maintain normal dynamics of the FtsZ scaffold and divisome functionality in C. crescentus. In addition to supporting FtsA function, we show that GroESL is required to maintain the flow of peptidoglycan precursors into the growing cell wall. Linking a chaperone to cell division may be a conserved way to coordinate environmental and internal cues that signal when it is safe to divide.ImportanceAll organisms depend on mechanisms that protect proteins from misfolding and aggregation. GroESL is a highly conserved molecular chaperone that functions to prevent protein aggregation in organisms ranging from bacteria to humans. Despite detailed biochemical understanding of GroESL function, the in vivo pathways that strictly depend on this chaperone remain poorly defined in most species. This study provides new insights into how GroESL is linked to the bacterial cell division machinery, a crucial target of current and future antimicrobial agents. We identify a functional interaction between GroESL and FtsA, a conserved bacterial actin homologue, suggesting that as in eukaryotes, some bacteria exhibit a connection between cytoskeletal actin proteins and chaperonins. Our work further defines how GroESL is integrated with cell wall synthesis, and illustrates how highly conserved folding machines ensure the functioning of fundamental cellular processes during stress.

scholarly journals A comprehensive evolutionary scenario of cell division and associated processes in the Firmicutes

2021 ◽  
Author(s):  
Pierre S Garcia ◽  
Wandrille Duchemin ◽  
Jean-Pierre Flandrois ◽  
Simonetta Gribaldo ◽  
Christophe Grangeasse ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Wall ◽  
Cell Division ◽  
Experimental Studies ◽  
In Silico Analysis ◽  
Cell Wall Synthesis ◽  
Cellular Processes ◽  
Phylogenetic Profiles ◽  
Phylogenetic Reconciliation ◽  
Bacterial Cell Cycle

Abstract The cell cycle is a fundamental process that has been extensively studied in bacteria. However, many of its components and their interactions with machineries involved in other cellular processes are poorly understood. Furthermore, most knowledge relies on the study of a few models, but the real diversity of the cell division apparatus and its evolution are largely unknown. Here, we present a massive in-silico analysis of cell division and associated processes in around 1,000 genomes of the Firmicutes, a major bacterial phylum encompassing models (i.e. Bacillus subtilis, Streptococcus pneumoniae, and Staphylococcus aureus), as well as many important pathogens. We analyzed over 160 proteins by using an original approach combining phylogenetic reconciliation, phylogenetic profiles, and gene cluster survey. Our results reveal the presence of substantial differences among clades and pinpoints a number of evolutionary hotspots. In particular, the emergence of Bacilli coincides with an expansion of the gene repertoires involved in cell wall synthesis and remodeling. We also highlight major genomic rearrangements at the emergence of Streptococcaceae. We establish a functional network in Firmicutes that allows identifying new functional links inside one same process such as between FtsW (peptidoglycan polymerase) and a previously undescribed PBP or between different processes, such as replication and cell wall synthesis. Finally, we identify new candidates involved in sporulation and cell wall synthesis. Our results provide a previously undescribed view on the diversity of the bacterial cell cycle, testable hypotheses for further experimental studies, and a methodological framework for the analysis of any other biological system.

scholarly journals The DUF1013 protein TrcR tracks with RNA polymerase to control the bacterial cell cycle and protect against antibiotics

2021 ◽  
Vol 118 (8) ◽  
pp. e2010357118
Author(s):  
Marie Delaby ◽  
Lydia M. Varesio ◽  
Laurence Degeorges ◽  
Sean Crosson ◽  
Patrick H. Viollier
Keyword(s):  
Cell Cycle ◽  
Rna Polymerase ◽  
Bacterial Cell ◽  
Efflux Pump ◽  
Caulobacter Crescentus ◽  
Transcription Elongation ◽  
Dependent Manner ◽  
Multidrug Efflux Pump ◽  
Bacterial Cell Cycle

How DNA-dependent RNA polymerase (RNAP) acts on bacterial cell cycle progression during transcription elongation is poorly investigated. A forward genetic selection for Caulobacter crescentus cell cycle mutants unearthed the uncharacterized DUF1013 protein (TrcR, transcriptional cell cycle regulator). TrcR promotes the accumulation of the essential cell cycle transcriptional activator CtrA in late S-phase but also affects transcription at a global level to protect cells from the quinolone antibiotic nalidixic acid that induces a multidrug efflux pump and from the RNAP inhibitor rifampicin that blocks transcription elongation. We show that TrcR associates with promoters and coding sequences in vivo in a rifampicin-dependent manner and that it interacts physically and genetically with RNAP. We show that TrcR function and its RNAP-dependent chromatin recruitment are conserved in symbiotic Sinorhizobium sp. and pathogenic Brucella spp. Thus, TrcR represents a hitherto unknown antibiotic target and the founding member of the DUF1013 family, an uncharacterized class of transcriptional regulators that track with RNAP during the elongation phase to promote transcription during the cell cycle.

scholarly journals The Chaperonin GroESL Facilitates Caulobacter crescentus Cell Division by Supporting the Functions of the Z-Ring Regulators FtsA and FzlA

mBio ◽  
2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Kristen Schroeder ◽  
Kristina Heinrich ◽  
Ines Neuwirth ◽  
Kristina Jonas
Keyword(s):  
Cell Cycle ◽  
Cell Wall ◽  
Cell Division ◽  
Bacterial Cell ◽  
Antimicrobial Agents ◽  
Caulobacter Crescentus ◽  
Content Type ◽  
Growing Cell ◽  
Z Ring ◽  
Bacterial Cell Cycle

ABSTRACT The highly conserved chaperonin GroESL performs a crucial role in protein folding; however, the essential cellular pathways that rely on this chaperone are underexplored. Loss of GroESL leads to severe septation defects in diverse bacteria, suggesting the folding function of GroESL may be integrated with the bacterial cell cycle at the point of cell division. Here, we describe new connections between GroESL and the bacterial cell cycle using the model organism Caulobacter crescentus. Using a proteomics approach, we identify candidate GroESL client proteins that become insoluble or are degraded specifically when GroESL folding is insufficient, revealing several essential proteins that participate in cell division and peptidoglycan biosynthesis. We demonstrate that other cell cycle events, such as DNA replication and chromosome segregation, are able to continue when GroESL folding is insufficient. We further find that deficiency of two FtsZ-interacting proteins, the bacterial actin homologue FtsA and the constriction regulator FzlA, mediate the GroESL-dependent block in cell division. Our data show that sufficient GroESL is required to maintain normal dynamics of the FtsZ scaffold and divisome functionality in C. crescentus. In addition to supporting divisome function, we show that GroESL is required to maintain the flow of peptidoglycan precursors into the growing cell wall. Linking a chaperone to cell division may be a conserved way to coordinate environmental and internal cues that signal when it is safe to divide. IMPORTANCE All organisms depend on mechanisms that protect proteins from misfolding and aggregation. GroESL is a highly conserved molecular chaperone that functions to prevent protein aggregation in organisms ranging from bacteria to humans. Despite detailed biochemical understanding of GroESL function, the in vivo pathways that strictly depend on this chaperone remain poorly defined in most species. This study provides new insights into how GroESL is linked to the bacterial cell division machinery, a crucial target of current and future antimicrobial agents. We identify a functional interaction between GroESL and the cell division proteins FzlA and FtsA, which modulate Z-ring function. FtsA is a conserved bacterial actin homologue, suggesting that as in eukaryotes, some bacteria exhibit a connection between cytoskeletal actin proteins and chaperonins. Our work further defines how GroESL is integrated with cell wall synthesis and illustrates how highly conserved folding machines ensure the functioning of fundamental cellular processes during stress.

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