OpgH is an essential regulator of Caulobacter morphology.

Bacterial growth and division rely on intricate regulation of morphogenetic complexes to remodel the cell envelope without compromising envelope integrity. Significant progress has been made in recent years towards understanding the regulation of cell wall metabolic enzymes. However, other cell envelope components play a role in morphogenesis as well. A primary factor required to protect envelope integrity in low osmolarity environments is OpgH, the synthase of osmoregulated periplasmic glucans (OPGs). Here, we demonstrate that OpgH is essential in the α-proteobacterium Caulobacter crescentus. Unexpectedly, depletion of OpgH or attempted complementation with a catalytically dead OpgH variant results in striking asymmetric bulging and cell lysis. These shape defects are accompanied by reduced cell wall synthesis and mislocalization of morphogenetic complexes. Interestingly, overactivation of the CenKR two-component system that has been implicated in cell envelope stress homeostasis in α-proteobacteria phenocopies the morphogenetic defects associated with OpgH depletion. Each of these perturbations leads to an increase in the levels of the elongasome protein, MreB, and decreases in the levels of divisome proteins FtsZ and MipZ as well as OpgH, itself. Constitutive production of OpgH during CenKR overactivation prevents cell bulging, but cells still exhibit morphogenetic defects. We propose that OPG depletion activates CenKR, leading to changes in the expression of cell envelope-related genes, but that OPGs also exert CenKR-independent effects on morphogenesis. Our data establish a surprising function for an OpgH homolog in morphogenesis and reveal an essential role of OpgH in maintaining cell morphology in Caulobacter.IMPORTANCEBacteria must synthesize and fortify the cell envelope in a tightly regulated manner to orchestrate growth and adaptation. Osmoregulated periplasmic glucans (OPGs) are important, but poorly understood, constituents of Gram-negative cell envelopes that contribute to envelope integrity and protect against osmotic stress. Here, we determined that the OPG synthase OpgH plays a surprising, essential role in morphogenesis in Caulobacter crescentus. Loss of OpgH causes asymmetric cell bulging and lysis via misregulation of the localization and activity of morphogenetic complexes. Overactivation of the CenKR two-component system involved in envelope homeostasis phenocopies OpgH depletion, suggesting that depletion of OpgH activates CenKR. Because cell envelope integrity is critical for bacterial survival, understanding how OpgH activity contributes to morphogenesis and maintenance of envelope integrity could aid in the development of antibiotic therapies.

Building the Bacterial Divisome at the Septum.

Across living organisms, division is necessary for cell survival and passing heritable information to the next generation. For this reason, cell division is highly conserved among eukaryotes and prokaryotes. Among the most highly conserved cell division proteins in eukaryotes are tubulin and actin. Tubulin polymerizes to form microtubules, which assemble into cytoskeletal structures in eukaryotes, such as the mitotic spindle that pulls chromatids apart during mitosis. Actin polymerizes to form a morphological framework for the eukaryotic cell, or cytoskeleton, that undergoes reorganization during mitosis. In prokaryotes, two of the most highly conserved cell division proteins are the tubulin homolog FtsZ and the actin homolog FtsA. In this chapter, the functions of the essential bacterial cell division proteins FtsZ and FtsA and their roles in assembly of the divisome at the septum, the site of cell division, will be discussed. In most bacteria, including Escherichia coli, the tubulin homolog FtsZ polymerizes at midcell, and this step is crucial for recruitment of many other proteins to the division site. For this reason, both FtsZ abundance and polymerization are tightly regulated by a variety of proteins. The actin-like FtsA protein polymerizes and tethers FtsZ polymers to the cytoplasmic membrane. Additionally, FtsA interacts with later stage cell division proteins, which are essential for division and for building the new cell wall at the septum. Recent studies have investigated how actin-like polymerization of FtsA on the lipid membrane may impact division, and we will discuss this and other ways that division in bacteria is regulated through FtsZ and FtsA.

Modulation of the lytic apparatus by the FtsEX complex within the bacterial division machinery.

The FtsEX membrane complex constitutes an essential component of the ABC transporter superfamily, widely distributed among bacterial species. It governs peptidoglycan degradation for cell division, acting as a signal transmitter rather than a substrate transporter. Through the ATPase activity of FtsE, it facilitates signal transmission from the cytosol across the membrane to the periplasm, activating associated peptidoglycan hydrolases. This review concentrates on the latest structural advancements elucidating the architecture of the FtsEX complex and its interplay with lytic enzymes or regulatory counterparts. The revealed three-dimensional structures unveil a landscape wherein a precise array of intermolecular interactions, preserved across diverse bacterial species, afford meticulous spatial and temporal control over the cell division process.

Lytic transglycosylase Slt of Pseudomonas aeruginosa as a periplasmic hub protein.

Peptidoglycan is a major constituent of the bacterial cell wall. Its integrity as a polymeric edifice is critical for bacterial survival and, as such, it is a preeminent target for antibiotics. The peptidoglycan is a dynamic crosslinked polymer that undergoes constant biosynthesis and turnover. The soluble lytic transglycosylase (Slt) of Pseudomonas aeruginosa is a periplasmic enzyme involved in this dynamic turnover. Using amber-codon-suppression methodology in live bacteria, we incorporated a fluorescent chromophore into the structure of Slt. Fluorescent microscopy shows that Slt populates the length of the periplasmic space and concentrates at the sites of septation in daughter cells. This concentration persists after separation of the cells. Amber-codon-suppression methodology was also used to incorporate a photoaffinity amino acid for the capture of partner proteins. Mass-spectrometry-based proteomics identified 12 partners for Slt in vivo. These proteomics experiments were complemented with in vitro pulldown analyses. Twenty additional partners were identified. We cloned the genes and purified to homogeneity 22 identified partners. Biophysical characterization confirmed all as bona fide Slt binders. The identities of the protein partners of Slt span disparate periplasmic protein families, inclusive of several proteins known to be present in the divisome. Notable periplasmic partners (KD < 0.5 µM) include PBPs (PBP1a, KD = 0.07 µM; PBP5 = 0.4 µM); other lytic transglycosylases (SltB2, KD = 0.09 µM; RlpA, KD = 0.4 µM); a type VI secretion system effector (Tse5, KD = 0.3 µM); and a regulatory protease for alginate biosynthesis (AlgO, KD < 0.4 µM). In light of the functional breadth of its interactome, Slt is conceptualized as a hub protein within the periplasm.

The divergent early divisome: is there a functional core?

The bacterial divisome is a complex nanomachine that drives cell division and separation. The essentiality of these processes leads to the assumption that proteins with core roles will be strictly conserved across all bacterial genomes. However, recent studies in diverse proteobacteria have revealed considerable variation in the early divisome compared with Escherichia coli. While some proteins are highly conserved, their specific functions and interacting partners vary. Meanwhile, different subphyla use clade-specific proteins with analogous functions. Thus, instead of focusing on gene conservation, we must also explore how key functions are maintained during early division by diverging protein networks. An enhanced awareness of these complex genetic networks will clarify the physical and evolutionary constraints of bacterial division.

Plasticity in the cell division processes of obligate intracellular bacteria.

Most bacteria divide through a highly conserved process called binary fission, in which there is symmetric growth of daughter cells and the synthesis of peptidoglycan at the mid-cell to enable cytokinesis. During this process, the parental cell replicates its chromosomal DNA and segregates replicated chromosomes into the daughter cells. The mechanisms that regulate binary fission have been extensively studied in several model organisms, including Eschericia coli, Bacillus subtilis, and Caulobacter crescentus. These analyses have revealed that a multi-protein complex called the divisome forms at the mid-cell to enable peptidoglycan synthesis and septation during division. In addition, rod-shaped bacteria form a multi-protein complex called the elongasome that drives sidewall peptidoglycan synthesis necessary for the maintenance of rod shape and the lengthening of the cell prior to division. In adapting to their intracellular niche, the obligate intracellular bacteria discussed here have eliminated one to several of the divisome gene products essential for binary fission in E. coli. In addition, genes that encode components of the elongasome, which were mostly lost as rod-shaped bacteria evolved into coccoid organisms, have been retained during the reductive evolutionary process that some coccoid obligate intracellular bacteria have undergone. Although the precise molecular mechanisms that regulate the division of obligate intracellular bacteria remain undefined, the studies summarized here indicate that obligate intracellular bacteria exhibit remarkable plasticity in their cell division processes.

The roles of GpsB and DivIVA in Staphylococcus aureus growth and division.

The spheroid bacterium Staphylococcus aureus is often used as a model of morphogenesis due to its apparently simple cell cycle. S. aureus has many cell division proteins that are conserved across bacteria alluding to common functions. However, despite intensive study, we still do not know the roles of many of these components. Here, we have examined the functions of the paralogues DivIVA and GpsB in the S. aureus cell cycle. Cells lacking gpsB display a more spherical phenotype than the wild-type cells, which is associated with a decrease in peripheral cell wall peptidoglycan synthesis. This correlates with increased localization of penicillin-binding proteins at the developing septum, notably PBPs 2 and 3. Our results highlight the role of GpsB as an apparent regulator of cell morphogenesis in S. aureus.

Amber-codon suppression for spatial localization and in vivo photoaffinity capture of the interactome of the Pseudomonas aeruginosa rare lipoprotein A lytic transglycosylase.

The 11 lytic transglycosylases of Pseudomonas aeruginosa have overlapping activities in the turnover of the cell-wall peptidoglycan. Rare lipoprotein A (RlpA) is distinct among the 11 by its use of only peptidoglycan lacking peptide stems. The spatial localization of RlpA and its interactome within P. aeruginosa are unknown. We employed suppression of introduced amber codons at sites in the rlpA gene for the introduction of the unnatural-amino-acids Νζ -[(2-azidoethoxy)carbonyl]-l-lysine (compound 1) and Nζ -[[[3-(3-methyl-3H-diazirin-3-yl)propyl]amino]carbonyl]-l-lysine (compound 2). In live P. aeruginosa, full-length RlpA incorporating compound 1 into its sequence was fluorescently tagged using strained-promoted alkyne-azide cycloaddition and examined by fluorescence microscopy. RlpA is present at low levels along the sidewall length of the bacterium, and at higher levels at the nascent septa of replicating bacteria. In intact P. aeruginosa, UV photolysis of full-length RlpA having compound 2 within its sequence generated a transient reactive carbene, which engaged in photoaffinity capture of neighboring proteins. Thirteen proteins were identified. Three of these proteins-PBP1a, PBP5, and MreB-are members of the bacterial divisome. The use of the complementary methodologies of non-canonical amino-acid incorporation, photoaffinity proximity analysis, and fluorescent microscopy confirm a dominant septal location for the RlpA enzyme of P. aeruginosa, as a divisome-associated activity. This accomplishment adds to the emerging recognition of the value of these methodologies for identification of the intracellular localization of bacterial proteins.

Molecular Cytology of 'Little Animals': Personal Recollections of Escherichia coli (and Bacillus subtilis).

This article relates personal recollections and starts with the origin of electron microscopy in the sixties of the previous century at the University of Amsterdam. Novel fixation and embedding techniques marked the discovery of the internal bacterial structures not visible by light microscopy. A special status became reserved for the freeze-fracture technique. By freeze-fracturing chemically fixed cells, it proved possible to examine the morphological effects of fixation. From there on, the focus switched from bacterial structure as such to their cell cycle. This invoked bacterial physiology and steady-state growth combined with electron microscopy. Electron-microscopic autoradiography with pulses of [3H] Dap revealed that segregation of replicating DNA cannot proceed according to a model of zonal growth (with envelope-attached DNA). This stimulated us to further investigate the sacculus, the peptidoglycan macromolecule. In particular, we focused on the involvement of penicillin-binding proteins such as PBP2 and PBP3, and their role in division. Adding aztreonam (an inhibitor of PBP3) blocked ongoing divisions but not the initiation of new ones. A PBP3-independent peptidoglycan synthesis (PIPS) appeared to precede a PBP3-dependent step. The possible chemical nature of PIPS is discussed.

SepT, a novel protein specific to multicellular cyanobacteria, influences peptidoglycan growth and septal nanopore formation in Anabaena sp. PCC 7120.

IMPORTANCE: Multicellular organization is a requirement for the development of complex organisms, and filamentous cyanobacteria such as Anabaena represent a paradigmatic case of bacterial multicellularity. The Anabaena filament can include hundreds of communicated cells that exchange nutrients and regulators and, depending on environmental conditions, can include different cell types specialized in distinct biological functions. Hence, the specific features of the Anabaena filament and how they are propagated during cell division represent outstanding biological issues. Here, we studied SepT, a novel coiled-coil-rich protein of Anabaena that is located in the intercellular septa and influences the formation of the septal specialized structures that allow communication between neighboring cells along the filament, a fundamental trait for the performance of Anabaena as a multicellular organism.

FtsE, the Nucleotide Binding Domain of the ABC Transporter Homolog FtsEX, Regulates Septal PG Synthesis in E. coli.

The peptidoglycan (PG) layer, a crucial component of the tripartite E.coli envelope, is required to maintain cellular integrity, protecting the cells from mechanical stress resulting from intracellular turgor pressure. Thus, coordinating synthesis and hydrolysis of PG during cell division (septal PG) is crucial for bacteria. The FtsEX complex directs septal PG hydrolysis through the activation of amidases; however, the mechanism and regulation of septal PG synthesis are unclear. In addition, how septal PG synthesis and hydrolysis are coordinated has remained unclear. Here, we have shown that overexpression of FtsE leads to a mid-cell bulging phenotype in E.coli, which is different from the filamentous phenotype observed during overexpression of other cell division proteins. Silencing of the common PG synthesis genes murA and murB reduced bulging, confirming that this phenotype is due to excess PG synthesis. We further demonstrated that septal PG synthesis is independent of FtsE ATPase activity and FtsX. These observations and previous results suggest that FtsEX plays a role during septal PG hydrolysis, whereas FtsE alone coordinates septal PG synthesis. Overall, our study findings support a model in which FtsE plays a role in coordinating septal PG synthesis with bacterial cell division. IMPORTANCE The peptidoglycan (PG) layer is an essential component of the E.coli envelope that is required to maintain cellular shape and integrity. Thus, coordinating PG synthesis and hydrolysis at the mid-cell (septal PG) is crucial during bacterial division. The FtsEX complex directs septal PG hydrolysis through the activation of amidases; however, its role in regulation of septal PG synthesis is unclear. Here, we demonstrate that overexpression of FtsE in E.coli leads to a mid-cell bulging phenotype due to excess PG synthesis. This phenotype was reduced upon silencing of common PG synthesis genes murA and murB. We further demonstrated that septal PG synthesis is independent of FtsE ATPase activity and FtsX. These observations suggest that the FtsEX complex plays a role during septal PG hydrolysis, whereas FtsE alone coordinates septal PG synthesis. Our study indicates that FtsE plays a role in coordinating septal PG synthesis with bacterial cell division.

The structural integrity of the membrane-embedded bacterial division complex FtsQBL studied with molecular dynamics simulations.

The FtsQBL is an essential molecular complex sitting midway through bacterial divisome assembly. To visualize and understand its structure, and the consequences of its membrane anchorage, we produced a model of the E. coli complex using the deep-learning prediction utility, AlphaFold 2. The heterotrimeric model was inserted into a 3-lipid model membrane and subjected to a 500-ns atomistic molecular dynamics simulation. The model is superb in quality and captures most experimentally derived structural features, at both the secondary structure and the side-chain levels. The model consists of a uniquely interlocking module contributed by the C-terminal regions of all three proteins. The functionally important constriction control domain residues of FtsB and FtsL are located at a fixed vertical position of ∼43-49 Å from the membrane surface. While the periplasmic domains of all three proteins are well-defined and rigid, the single transmembrane helices of each are flexible and their collective twisting and bending contribute to most structural variations, according to principal component analysis. Considering FtsQ only, the protein is more flexible in its free state relative to its complexed state-with the biggest structural changes located at the elbow between the transmembrane helix and the α-domain. The disordered N-terminal domains of FtsQ and FtsL associate with the cytoplasmic surface of the inner membrane instead of freely venturing into the solvent. Contact network analysis highlighted the formation of the interlocking trimeric module in FtsQBL as playing a central role in mediating the overall structure of the complex.

The SepF-like proteins SflA and SflB prevent ectopic localization of FtsZ and DivIVA during sporulation of Streptomyces coelicolor.

Bacterial cytokinesis starts with the polymerization of the tubulin-like FtsZ, which forms the cell division scaffold. SepF aligns FtsZ polymers and also acts as a membrane anchor for the Z-ring. While in most bacteria cell division takes place at midcell, during sporulation of Streptomyces many septa are laid down almost simultaneously in multinucleoid aerial hyphae. The genomes of streptomycetes encode two additional SepF paralogs, SflA and SflB, which can interact with SepF. Here we show that the sporogenic aerial hyphae of sflA and sflB mutants of Streptomyces coelicolor frequently branch, a phenomenon never seen in the wild-type strain. The branching coincided with ectopic localization of DivIVA along the lateral wall of sporulating aerial hyphae. Constitutive expression of SflA and SflB largely inhibited hyphal growth, further correlating SflAB activity to that of DivIVA. SflAB localized in foci prior to and after the time of sporulation-specific cell division, while SepF co-localized with active septum synthesis. Foci of FtsZ and DivIVA frequently persisted between adjacent spores in spore chains of sflA and sflB mutants, at sites occupied by SflAB in wild-type cells. Taken together, our data show that SflA and SflB play an important role in the control of growth and cell division during Streptomyces development.

MipZ caps the plus-end of FtsZ polymers to promote their rapid disassembly.

The spatiotemporal regulation of cell division is a fundamental issue in cell biology. Bacteria have evolved a variety of different systems to achieve proper division site placement. In many cases, the underlying molecular mechanisms are still incompletely understood. In this study, we investigate the function of the cell division regulator MipZ from Caulobacter crescentus, a P-loop ATPase that inhibits the polymerization of the treadmilling tubulin homolog FtsZ near the cell poles, thereby limiting the assembly of the cytokinetic Z ring to the midcell region. We show that MipZ interacts with FtsZ in both its monomeric and polymeric forms and induces the disassembly of FtsZ polymers in a manner that is not dependent but enhanced by the FtsZ GTPase activity. Using a combination of biochemical and genetic approaches, we then map the MipZ-FtsZ interaction interface. Our results reveal that MipZ employs a patch of surface-exposed hydrophobic residues to interact with the C-terminal region of the FtsZ core domain. In doing so, it sequesters FtsZ monomers and caps the (+)-end of FtsZ polymers, thereby promoting their rapid disassembly. We further show that MipZ influences the conformational dynamics of interacting FtsZ molecules, which could potentially contribute to modulating their assembly kinetics. Together, our findings show that MipZ uses a combination of mechanisms to control FtsZ polymerization, which may be required to robustly regulate the spatiotemporal dynamics of Z ring assembly within the cell.

Enzyme 1 of the phosphoenolpyruvate:sugar phosphotransferase system is involved in resistance to MreB disruption in wild-type and ∆envC cells.

Cell wall synthesis in bacteria is determined by two protein complexes: the elongasome and divisome. The elongasome is coordinated by the actin homolog MreB while the divisome is organized by the tubulin homolog FtsZ. While these two systems must coordinate with each other to ensure that elongation and division are coregulated, this cross talk has been understudied. Using the MreB depolymerizing agent, A22, we found that multiple gene deletions result in cells exhibiting increased sensitivity to MreB depolymerization. One of those genes encodes for EnvC, a part of the divisome that is responsible for splitting daughter cells after the completion of cytokinesis through the activation of specific amidases. Here we show this increased sensitivity to A22 works through two known amidase targets of EnvC: AmiA and AmiB. In addition, suppressor analysis revealed that mutations in enzyme 1 of the phosphoenolpyruvate:sugar phosphotransferase system (PTS) can suppress the effects of A22 in both wild-type and envC deletion cells. Together this work helps to link elongation, division, and metabolism.

Regulation of Lytic Machineries by the FtsEX Complex in the Bacterial Divisome.

The essential membrane complex FtsE/FtsX (FtsEX), belonging to the ABC transporter superfamily and widespread among bacteria, plays a relevant function in some crucial cell wall remodeling processes such as cell division, elongation, or sporulation. FtsEX plays a double role by recruiting proteins to the divisome apparatus and by regulating lytic activity of the cell wall hydrolases required for daughter cell separation. Interestingly, FtsEX does not act as a transporter but uses the ATPase activity of FtsE to mechanically transmit a signal from the cytosol, through the membrane, to the periplasm that activates the attached hydrolases. While the complete molecular details of such mechanism are not yet known, evidence has been recently reported that clarify essential aspects of this complex system. In this chapter we will present recent structural advances on this topic. The three-dimensional structure of FtsE, FtsX, and some of the lytic enzymes or their cognate regulators revealed an unexpected scenario in which a delicate set of intermolecular interactions, conserved among different bacterial genera, could be at the core of this regulatory mechanism providing exquisite control in both space and time of this central process to assist bacterial survival.

A proteolytic pathway coordinates cell division and heterocyst differentiation in the cyanobacterium Anabaena sp. PCC 7120.

The filamentous, multicellular cyanobacterium Anabaena sp. PCC 7120 (Anabaena) is a prokaryotic model for the study of cell differentiation and cell-cell interactions. Upon combined-nitrogen deprivation, Anabaena forms a particular cell type, heterocyst, for aerobic nitrogen fixation. Heterocysts are semiregularly spaced among vegetative cells. Heterocyst differentiation is coupled to cell division, but the underlying mechanism remains unclear. This mechanism could be mediated by the putative protease HetF, which is a divisome component and is necessary for heterocyst differentiation. In this study, by suppressor screening, we identified PatU3, as a negative regulator acting downstream of HetF for cell division and heterocyst development. The inactivation of patU3 restored the capacity of cell division and heterocyst differentiation in the ΔhetF mutant, and overexpression of patU3 inhibited both processes in the wild-type background. We demonstrated that PatU3 was a specific substrate of the protease activity of HetF. Consequently, PatU3 accumulated in the hetF-deficient mutant, which was responsible for the resultant mutant phenotype. The cleavage site of PatU3 by HetF was mapped after the Arg117 residue, whose mutation made PatU3 resistant to HetF processing, and mimicked the effect of hetF deletion. Our results provided evidence that HetF regulated cell division and heterocyst differentiation by controlling the inhibitory effects of PatU3. This proteolytic pathway constituted a mechanism for the coordination between cell division and differentiation in a prokaryotic model used for studies on developmental biology and multicellularity.

The structural dynamics of full-length divisome transmembrane proteins FtsQ, FtsB, and FtsL in FtsQBL complex formation.

FtsQBL is a transmembrane protein complex in the divisome of Escherichia coli that plays a critical role in regulating cell division. Although extensive efforts have been made to investigate the interactions between the three involved proteins, FtsQ, FtsB, and FtsL, the detailed interaction mechanism is still poorly understood. In this study, we used hydrogen-deuterium exchange mass spectrometry to investigate these full-length proteins and their complexes. We also dissected the structural dynamic changes and the related binding interfaces within the complexes. Our data revealed that FtsB and FtsL interact at both the periplasmic and transmembrane regions to form a stable complex. Furthermore, the periplasmic region of FtsB underwent significant conformational changes. With the help of computational modeling, our results suggest that FtsBL complexation may bring the respective constriction control domains (CCDs) in close proximity. We show that when FtsBL adopts a coiled-coil structure, the CCDs are fixed at a vertical position relative to the membrane surface; thus, this conformational change may be essential for FtsBL's interaction with other divisome proteins. In the FtsQBL complex, intriguingly, we show only FtsB interacts with FtsQ at its C-terminal region, which stiffens a large area of the ß-domain of FtsQ. Consistent with this, we found the connection between the α- and ß-domains in FtsQ is also strengthened in the complex. Overall, the present study provides important experimental evidence detailing the local interactions between the full-length FtsB, FtsL, and FtsQ protein, as well as valuable insights into the roles of FtsQBL complexation in regulating divisome activity.

FtsZ at mid-cell is essential in Escherichia coli until the late stage of constriction.

There has been recent debate as to the source of constriction force during cell division. FtsZ can generate a constriction force on tubular membranes in vitro, suggesting it may generate the constriction force in vivo. However, another study showed that mutants of FtsZ did not affect the rate of constriction, whereas mutants of the PG assembly did, suggesting that PG assembly may push the constriction from the outside. Supporting this model, two groups found that cells that have initiated constriction can complete septation while the Z ring is poisoned with the FtsZ targeting antibiotic PC190723. PC19 arrests treadmilling but leaves FtsZ in place. We sought to determine if a fully assembled Z ring is necessary during constriction. To do this, we used a temperature-sensitive FtsZ mutant, FtsZ84. FtsZ84 supports cell division at 30 °C, but it disassembles from the Z ring within 1 min upon a temperature jump to 42 °C. Following the temperature jump we found that cells in early constriction stop constricting. Cells that had progressed to the later stage of division finished constriction without a Z ring. These results show that in Escherichia coli, an assembled Z ring is essential for constriction except in the final stage, contradicting the simplest interpretation of previous studies using PC19.

Filamentous Thermosensitive Mutant Z: An Appealing Target for Emerging Pathogens and a Trek on Its Natural Inhibitors.

Antibiotic resistance is a major emerging issue in the health care sector, as highlighted by the WHO. Filamentous Thermosensitive mutant Z (Fts-Z) is gaining significant attention in the scientific community as a potential anti-bacterial target for fighting antibiotic resistance among several pathogenic bacteria. The Fts-Z plays a key role in bacterial cell division by allowing Z ring formation. Several in vitro and in silico experiments have demonstrated that inhibition of Fts-Z can lead to filamentous growth of the cells, and finally, cell death occurs. Many natural compounds that have successfully inhibited Fts-Z are also studied. This review article intended to highlight the structural-functional aspect of Fts-Z that leads to Z-ring formation and its contribution to the biochemistry and physiology of cells. The current trend of natural inhibitors of Fts-Z protein is also covered.