scholarly journals An essential Staphylococcus aureus cell division protein directly regulates FtsZ dynamics

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Prahathees J Eswara ◽  
Robert S Brzozowski ◽  
Marissa G Viola ◽  
Gianni Graham ◽  
Catherine Spanoudis ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Division ◽  
Cell Lysis ◽  
Regulatory Proteins ◽  
Binary Fission ◽  
Gtpase Activity ◽  
Human Pathogen ◽  
The Core ◽  
Z Ring ◽  
Cell Division Protein

Binary fission has been well studied in rod-shaped bacteria, but the mechanisms underlying cell division in spherical bacteria are poorly understood. Rod-shaped bacteria harbor regulatory proteins that place and remodel the division machinery during cytokinesis. In the spherical human pathogen Staphylococcus aureus, we found that the essential protein GpsB localizes to mid-cell during cell division and co-constricts with the division machinery. Depletion of GpsB arrested cell division and led to cell lysis, whereas overproduction of GpsB inhibited cell division and led to the formation of enlarged cells. We report that S. aureus GpsB, unlike other Firmicutes GpsB orthologs, directly interacts with the core divisome component FtsZ. GpsB bundles and organizes FtsZ filaments and also stimulates the GTPase activity of FtsZ. We propose that GpsB orchestrates the initial stabilization of the Z-ring at the onset of cell division and participates in the subsequent remodeling of the divisome during cytokinesis.

scholarly journals High-resolution crystal structures of Escherichia coli FtsZ bound to GDP and GTP

2020 ◽  
Vol 76 (2) ◽  
pp. 94-102 ◽  
Author(s):  
Maria A. Schumacher ◽  
Tomoo Ohashi ◽  
Lauren Corbin ◽  
Harold P. Erickson
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Cell Division ◽  
High Resolution ◽  
Crystal Structures ◽  
Bacterial Cell ◽  
Model System ◽  
E Coli ◽  
Z Ring ◽  
Main Model

Bacterial cytokinesis is mediated by the Z-ring, which is formed by the prokaryotic tubulin homolog FtsZ. Recent data indicate that the Z-ring is composed of small patches of FtsZ protofilaments that travel around the bacterial cell by treadmilling. Treadmilling involves a switch from a relaxed (R) state, favored for monomers, to a tense (T) conformation, which is favored upon association into filaments. The R conformation has been observed in numerous monomeric FtsZ crystal structures and the T conformation in Staphylococcus aureus FtsZ crystallized as assembled filaments. However, while Escherichia coli has served as a main model system for the study of the Z-ring and the associated divisome, a structure has not yet been reported for E. coli FtsZ. To address this gap, structures were determined of the E. coli FtsZ mutant FtsZ(L178E) with GDP and GTP bound to 1.35 and 1.40 Å resolution, respectively. The E. coli FtsZ(L178E) structures both crystallized as straight filaments with subunits in the R conformation. These high-resolution structures can be employed to facilitate experimental cell-division studies and their interpretation in E. coli.

scholarly journals Daptomycin Exerts Bactericidal Activity without Lysis of Staphylococcus aureus

2008 ◽  
Vol 52 (6) ◽  
pp. 2223-2225 ◽  
Author(s):  
Nicole Cotroneo ◽  
Robert Harris ◽  
Nancy Perlmutter ◽  
Terry Beveridge ◽  
Jared A. Silverman
Keyword(s):  
Electron Microscopy ◽  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Cell Division ◽  
Bactericidal Activity ◽  
Membrane Integrity ◽  
Cell Lysis

ABSTRACT The ability of daptomycin to produce bactericidal activity against Staphylococcus aureus while causing negligible cell lysis has been demonstrated using electron microscopy and the membrane integrity probes calcein and ToPro3. The formation of aberrant septa on the cell wall, suggestive of impairment of the cell division machinery, was also observed.

scholarly journals The Cell Division Protein FtsZ fromStreptococcus pneumoniaeExhibits a GTPase Activity Delay

2015 ◽  
Vol 290 (41) ◽  
pp. 25081-25089 ◽  
Author(s):  
Estefanía Salvarelli ◽  
Marcin Krupka ◽  
Germán Rivas ◽  
Jesus Mingorance ◽  
Paulino Gómez-Puertas ◽  
...  
Keyword(s):  
Cell Division ◽  
Gtpase Activity ◽  
Cell Division Protein

scholarly journals Bacterial SOS Checkpoint Protein SulA Inhibits Polymerization of Purified FtsZ Cell Division Protein

1998 ◽  
Vol 180 (15) ◽  
pp. 3946-3953 ◽  
Author(s):  
Dorina Trusca ◽  
Solomon Scott ◽  
Chris Thompson ◽  
David Bramhill
Keyword(s):  
Escherichia Coli ◽  
Dna Damage ◽  
Control System ◽  
Cell Division ◽  
Gtpase Activity ◽  
Checkpoint Control ◽  
Checkpoint Protein ◽  
Point Mutant ◽  
Reversible Inhibition ◽  
Cell Division Protein

ABSTRACT Cell division of Escherichia coli is inhibited when the SulA protein is induced in response to DNA damage as part of the SOS checkpoint control system. The SulA protein interacts with the tubulin-like FtsZ division protein. We investigated the effects of purified SulA upon FtsZ. SulA protein inhibits the polymerization and the GTPase activity of FtsZ, while point mutant SulA proteins show little effect on either of these FtsZ activities. SulA did not inhibit the polymerization of purified FtsZ2 mutant protein, which was originally isolated as insensitive to SulA. These studies define polymerization assays for FtsZ which respond to an authentic cellular regulator. The observations presented here support the notion that polymerization of FtsZ is central to its cellular role and that direct, reversible inhibition of FtsZ polymerization by SulA may account for division inhibition.

scholarly journals SosA inhibits cell division inStaphylococcus aureusin response to DNA damage

2018 ◽  
Author(s):  
Martin S. Bojer ◽  
Katarzyna Wacnik ◽  
Peter Kjelgaard ◽  
Clement Gallay ◽  
Amy L. Bottomley ◽  
...  
Keyword(s):  
Amino Acids ◽  
Staphylococcus Aureus ◽  
Dna Damage ◽  
Cell Division ◽  
Inhibitory Activity ◽  
Cell Swelling ◽  
Bacterial Cells ◽  
Human Pathogen ◽  
Cell Division Inhibition ◽  
Cell Division Inhibitor

AbstractInhibition of cell division is critical for cell viability under DNA damaging conditions. In bacterial cells, DNA damage induces the SOS response, a process that inhibits cell division while repairs are being made. In coccoid bacteria, such as the human pathogenStaphylococcus aureus, the process remains poorly understood. Here we have characterized an SOS-induced cell-division inhibitor, SosA, inS. aureus. We find that in contrast to the wildtype,sosAmutant cells continue division under DNA damaging conditions with decreased viability as a consequence. Conversely, overproduction of SosA leads to cell division inhibition and reduced growth. The SosA protein is localized in the bacterial membrane and mutation of an extracellular amino acid, conserved between homologs of other staphylococcal species, abolished the inhibitory activity as did truncation of the C-terminal 30 amino acids. In contrast, C-terminal truncation of 10 amino acids lead to SosA accumulation and a strong cell division inhibitory activity. A similar phenotype was observed upon expression of wildtype SosA in a mutant lacking the membrane protease, CtpA. Thus, the extracellular C-terminus of SosA is required both for cell-division inhibition and for turnover of the protein. Functional studies showed that SosA is likely to interact with one or more divisome components and, without interfering with early cell-division events, halts cell division at a point where septum formation is initiated yet being unable to progress to septum closure. Our findings provide important insights into cell-division regulation in staphylococci that may foster development of new classes of antibiotics targeting this essential process.ImportanceStaphylococcus aureusis a serious human pathogen and a model organism for cell-division studies in spherical bacteria. We show that SosA is the DNA-damage-inducible cell-division inhibitor inS. aureusthat upon expression causes cell swelling and cessation of the cell cycle at a characteristic stage post septum initiation but prior to division plate completion. SosA appears to function via an extracellular activity and is likely to do so by interfering with the essential membrane-associated division proteins, while at the same time being negatively regulated by the membrane protease CtpA. This report represents the first description of the process behind cell-division inhibition in coccoid bacteria. As several pathogens are included in this category, uncovering the molecular details of SosA activity and control can lead to identification of new targets for development of valuable anti-bacterial drugs.

scholarly journals LocZ Is a New Cell Division Protein Involved in Proper Septum Placement in Streptococcus pneumoniae

mBio ◽  
2014 ◽  
Vol 6 (1) ◽  
Author(s):  
Nela Holečková ◽  
Linda Doubravová ◽  
Orietta Massidda ◽  
Virginie Molle ◽  
Karolína Buriánková ◽  
...  
Keyword(s):  
Cell Division ◽  
Streptococcus Pneumoniae ◽  
Protein Kinase ◽  
Bacterial Cell Division ◽  
Content Type ◽  
Daughter Cells ◽  
Division Site ◽  
Z Ring ◽  
Specific Shape ◽  
Cell Division Protein

ABSTRACTHow bacteria control proper septum placement at midcell, to guarantee the generation of identical daughter cells, is still largely unknown. Although different systems involved in the selection of the division site have been described in selected species, these do not appear to be widely conserved. Here, we report that LocZ (Spr0334), a newly identified cell division protein, is involved in proper septum placement inStreptococcus pneumoniae. We show thatlocZis not essential but that its deletion results in cell division defects and shape deformation, causing cells to divide asymmetrically and generate unequally sized, occasionally anucleated, daughter cells. LocZ has a unique localization profile. It arrives early at midcell, before FtsZ and FtsA, and leaves the septum early, apparently moving along with the equatorial rings that mark the future division sites. Consistently, cells lacking LocZ also show misplacement of the Z-ring, suggesting that it could act as a positive regulator to determine septum placement. LocZ was identified as a substrate of the Ser/Thr protein kinase StkP, which regulates cell division in S. pneumoniae. Interestingly, homologues of LocZ are found only in streptococci, lactococci, and enterococci, indicating that this close phylogenetically related group of bacteria evolved a specific solution to spatially regulate cell division.IMPORTANCEBacterial cell division is a highly ordered process regulated in time and space. Recently, we reported that the Ser/Thr protein kinase StkP regulates cell division in Streptococcus pneumoniae, through phosphorylation of several key proteins. Here, we characterized one of the StkP substrates, Spr0334, which we named LocZ. We show that LocZ is a new cell division protein important for proper septum placement and likely functions as a marker of the cell division site. Consistently, LocZ supports proper Z-ring positioning at midcell. LocZ is conserved only among streptococci, lactococci, and enterococci, which lack homologues of the Min and nucleoid occlusion effectors, indicating that these bacteria adapted a unique mechanism to find their middle, reflecting their specific shape and symmetry.

scholarly journals Influence of CrgA on Assembly of the Cell Division Protein FtsZ during Development of Streptomyces coelicolor

2006 ◽  
Vol 188 (4) ◽  
pp. 1540-1550 ◽  
Author(s):  
Ricardo Del Sol ◽  
Jonathan G. L. Mullins ◽  
Nina Grantcharova ◽  
Klas Flärdh ◽  
Paul Dyson
Keyword(s):  
Cell Division ◽  
Streptomyces Coelicolor ◽  
Orthologous Gene ◽  
Integral Membrane Protein ◽  
Origin Of Replication ◽  
Small Proteins ◽  
Aerial Hyphae ◽  
Z Ring ◽  
Cell Division Protein ◽  
Conserved Gene

ABSTRACT The product of the crgA gene of Streptomyces coelicolor represents a novel family of small proteins. A single orthologous gene is located close to the origin of replication of all fully sequenced actinomycete genomes and borders a conserved gene cluster implicated in cell growth and division. In S. coelicolor, CrgA is important for coordinating growth and cell division in sporogenic hyphae. In this study, we demonstrate that CrgA is an integral membrane protein whose peak expression is coordinated with the onset of development of aerial hyphae. The protein localizes to discrete foci away from growing hyphal tips. Upon overexpression, CrgA localizes to apical syncytial cells of aerial hyphae and inhibits the formation of productive cytokinetic rings of the bacterial tubulin homolog FtsZ, leading to proteolytic turnover of this major cell division determinant. In the absence of known prokaryotic cell division inhibitors in actinomycetes, CrgA may have an important conserved function influencing Z-ring formation in these bacteria.

scholarly journals Molecular dynamics simulation of GTPase activity in polymers of the cell division protein FtsZ

FEBS Letters ◽  
2012 ◽  
Vol 586 (8) ◽  
pp. 1236-1239 ◽  
Author(s):  
Fernando Martín-García ◽  
Estefanía Salvarelli ◽  
Jesús Ignacio Mendieta-Moreno ◽  
Miguel Vicente ◽  
Jesús Mingorance ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Cell Division ◽  
Molecular Dynamics Simulation ◽  
Dynamics Simulation ◽  
Gtpase Activity ◽  
Cell Division Protein

scholarly journals Author response: An essential Staphylococcus aureus cell division protein directly regulates FtsZ dynamics

2018 ◽  
Author(s):  
Prahathees J Eswara ◽  
Robert S Brzozowski ◽  
Marissa G Viola ◽  
Gianni Graham ◽  
Catherine Spanoudis ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Division ◽  
Author Response ◽  
Cell Division Protein

scholarly journals The Stress-Active Cell Division Protein ZapE Alters FtsZ Filament Architecture to Facilitate Division in Escherichia coli

2021 ◽  
Vol 12 ◽  
Author(s):  
Eric C. DiBiasio ◽  
Rebecca A. Dickinson ◽  
Catherine E. Trebino ◽  
Colby N. Ferreira ◽  
Josiah J. Morrison ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Cell Division ◽  
High Temperature ◽  
Environmental Stress ◽  
Atp Hydrolysis ◽  
Major Protein ◽  
Bacterial Cells ◽  
Z Ring ◽  
Cell Division Protein

During pathogenic infections, bacterial cells experience environmental stress conditions, including low oxygen and thermal stress. Bacterial cells proliferate during infection and divide by a mechanism characterized by the assembly of a large cytoskeletal structure at the division site called the Z-ring. The major protein constituting the Z-ring is FtsZ, a tubulin homolog and GTPase that utilizes the nucleotide to assemble into dynamic polymers. In Escherichia coli, many cell division proteins interact with FtsZ and modulate Z-ring assembly, while others direct cell wall insertion and peptidoglycan remodeling. Here, we show that ZapE, an ATPase that accumulates during late constriction, directly interacts with FtsZ and phospholipids in vitro. In the presence of adenosine triphosphate (ATP), ZapE induces bundling of GTP-induced FtsZ polymers; however, ZapE also binds FtsZ in the absence of GTP. The ZapE mutant protein ZapE(K84A), which is defective for ATP hydrolysis, also interacts with FtsZ and induces FtsZ filament bundling. In vivo, cultures of zapE deletion cells contain a low percentage of filamentous cells, suggesting that they have a modest division defect; however, they are able to grow when exposed to stress, such as high temperature and limited oxygen. When combined with the chromosomal deletion of minC, which encodes an FtsZ disassembly factor, ΔzapE ΔminC cells experience growth delays that slow proliferation at high temperature and prevent recovery. This synthetic slow growth phenotype after exposure to stress suggests that ZapE may function to ensure proliferation during and after stress, and this is exacerbated when cells are also deleted for minC. Expression of either ZapE or ZapE(K84A) complements the aberrant growth phenotypes in vivo suggesting that the division-associated role of ZapE does not require ZapE ATP hydrolysis. These results support that ZapE is a stress-regulated cell division protein that interacts directly with FtsZ and phospholipids, promoting growth and division after exposure to environmental stress.

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