Biology subjects

Bhattacharya, D.

Publications and source records attributed to Bhattacharya, D..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

Repurposing Melatonin in dual-mode for Wilson disease therapy as a Copper Chelator and an antioxidant agent

Loss-of-function mutations in copper-ATPase ATP7B underlie Wilson disease (WD), a disorder characterized by hepatic copper accumulation and severe hepato-neuropathology. Existing chelation therapeutics remove excess copper but lack intrinsic antioxidant capacity and frequently cause systemic toxicity. Here we evaluate melatonin, an FDA-approved indoleamine with antioxidant and putative metal-chelating activity, as a candidate therapeutic for WD. In ATP7B-/- hepatocytes, melatonin restored copper-induced reactive oxygen species (ROS) to basal levels, reduced apoptosis twofold, and attenuated Nrf2 nuclear translocation leading to reduction of Hemoxygenase-1 abundance. Live-cell ratiometric analysis of GSSG/GSH using GRX1-roGFP2 expressed in melatonin-treated ATP7B-/- hepatocytes revealed a significant reduction in intensity-ratio, indicating an effective mitigation of copper-induced glutathione oxidation. Isothermal calorimetric titration revealed moderate Cu2+ affinity (K ITC=4.54 x 103 M-{superscript 1}), rationalized by MD-simulations showing an interaction energy of 18.5 x 10-3 kcal{middle dot}mol-{superscript 1} via amide-Cu{superscript 2} coordination. In-cellulo studies also revealed that copper-induced vesicularized ATP7B reinstates to Golgi in melatonin-treated hepatocytes. In vivo, melatonin treatment reduced copper-induced oxidative stress in zebrafish embryos and lowered copper burden in Caenorhabditis elegans WD model. Our studies revealed that encapsulation of melatonin within an engineered polymeric nanocapsules having dithiol linkers, susceptible to cleavage by GSH, extended melatonins circulatory half-life ten-fold and enhanced its ROS-scavenging efficacy three-fold relative to free melatonin. This work introduces a unique dual-function therapeutic strategy that integrates antioxidant activity with copper chelation, simultaneously addressing copper overload and redox imbalance. Repurposing melatonin, with its established clinical safety, offers rapid and cost-effective translational pathway toward WD-therapy while providing a generalizable platform for redox- and metal-associated disorders.

cell biology↗

bioRxiv2025

Comparative genome analysis of tea rhizosphere dwelling Paenarthrobacter nicotinovorans AB444: Uncovering Physiological Resilience and Ecological Adaptability

Plant growth-promoting rhizobacteria (PGPR) can be considered a promising tool for sustainable agriculture. The recent scenario of growing demand for higher crop yields, with declining soil fertility and impacts of climate change, promotes the global shift towards eco-friendly agricultural practices, emphasising the significance of PGPR as a sustainable solution. In this study, a PGPR Paenarthrobacter sp. AB444 was isolated from the rhizosphere of tea plants at the Longview and Makaibari tea estates in the Darjeeling District of West Bengal. Based on the draft genome sequence along with comprehensive chemotaxonomic analyses, strain AB444 was identified as Paenarthrobacter nicotinovorans. The pangenomic analysis with phylogenetically close strains revealed the gene clusters that are common and unique to the isolate. The plant growth-promoting attributes of AB444 were explored with different assays like phosphate solubilisation, IAA and siderophore production, ACC deaminase, nitrogen fixation, and protease activity. The colonization of the isolate to the plant root and in-planta growth were also assessed. The presence of biosynthetic gene clusters of AB444 related to plant growth was also extensively studied, highlighting the unmapped disposition of Paenarthrobacter nicotinovorans.

microbiology↗

bioRxiv2025

Early, adjuvant-responsive epigenetic programs in B cells imprint subsequent plasma cell survival and the duration of humoral immunity

The duration of antibody production varies across different infections and vaccines. To define molecular programs that promote durable humoral immunity, we used mice deficient in ZBTB20, a transcription factor that is highly expressed by plasma cells and required to maintain antibody production in vivo. However, genetic deletion of Zbtb20 in long-lived plasma cells had no impact on the duration of antibody production. Instead, deletion of Zbtb20 in B cells only within the first week after immunization caused a subsequent failure to maintain plasma cells. Through single cell ATAC-sequencing, we observed elevated IRF8- and Ets-dependent epigenetic programs in ZBTB20-deficient B cells at 7 days post-immunization, whereas the corresponding transcriptional changes manifested ~1 week later. Switching from alum to an oil-in-water adjuvant suppressed Ets-dependent epigenetic programs and rescued ZBTB20-deficient antibody responses. Deletion of Irf8 also rescued ZBTB20-deficient antibody responses. Thus, B cell-intrinsic epigenetic programs imprint durable antibody production at a very early stage, prior to major transcriptional consequences and weeks before most long-lived plasma cells are formed.

immunology↗

bioRxiv2025

High Cross Pollination Frequency in Rice Landraces in Field Condition

Flower opening time (FOT) and the duration of florets remaining open (= flower exposure duration, FED) are crucially important for successful cross pollination between neighbouring rice plants. When the florets of the ovary parent (or pollen recipient) open even a few seconds after the closure of all the florets of the the pollen parent of a rice cultivar, the chances of cross pollination (CP) would obviously be zero. Conversely, as shown by our previous study, cross pollination frequency (CPF) would be very high (>80%) if the overlap of FEDs of the PP and OP is considerably long. In continuation of our previous study conducted in 2019, we subsequently conducted crossing experiments with 19 pairs of rice landraces during short-day flowering season and 8 pairs during long-day flowering season. The results show that with a long (>20 min) duration of FED overlap between OP and PP, the CPF tends to exceed 60%, often reaching 100%, although in some cases successful CP resulted in variable degrees of F1 sterility. These data confirm our previous report; and contradict the century-old received wisdom based on a series of crossing experiments, that CP in rice rarely exceeds 2%, as widely published in all textbooks and official literature in rice biology. Our experimental evidence show the actuality of naturally high CPF in rice under circumstances of considerable FED overlap between parental cultivars, and indicates the necessity of further exploration into genetic interactions of sterile grain production and assortments of polygenic traits in the offspring from crosses between different varietal genotypes.

plant biology↗

bioRxiv2025

Cannabinoid Receptor 2 Activating Antibodies: A Promising Therapeutic Strategy for Macrophage-Driven Fibro-Inflammatory Diseases

Fibrotic diseases, often fueled by chronic inflammation, represent a major unmet medical need. A critical driver of this process is the activation of macrophages, which secrete pro-inflammatory cytokines and chemokines, leading to immune cell recruitment and collagen deposition by myofibroblasts. Agonizing the cannabinoid receptor 2 (CB2), expressed on macrophages, offers a potential therapeutic avenue to suppress this activation. Despite widespread interest in CB2 modulation, challenges remain in the development of small molecule agonists, including insufficient specificity and poor drug-like properties. Antibodies are highly specific with favorable pharmacokinetics and bioavailability, but GPCR agonist antibodies have been difficult to discover. Here we present first-in-class CB2 agonist antibodies, AB120 and AB150. These antibodies are CB2 specific, G-alpha biased, and effectively decrease the expression of macrophage activation markers and key pro-inflammatory cytokines, including IL-6, IL-1{beta} and TNF-. Furthermore, using an ex vivo human precision-cut liver slice (hPCLS) model of liver fibrosis, we observe that treatment with these CB2 agonist antibodies not only reduces inflammatory markers but also decreases collagen expression, indicating a potential to halt or reverse fibrosis. These novel CB2-specific agonist antibodies hold promise as therapeutics for a range of fibrotic and inflammatory conditions driven by chronic macrophage activation and demonstrate the potential of GPCR antibody agonists to drug this challenging class of targets. Significance StatementFibrotic diseases driven by chronic inflammation lack effective treatments. CB2 agonism modulates macrophage activation to reduce pro-inflammatory cytokines suggesting a novel avenue of treatment, but small molecule CB2 agonists have faced substantial limitations due to off-target effects. We introduce two novel CB2-specific agonist antibodies with potent anti-inflammatory and anti-fibrotic effects in vitro and in a human ex vivo liver fibrosis model. These antibodies provide a promising new therapeutic strategy and highlight the advantages of antibodies as GPCR agonist drugs.

pharmacology and toxicology↗

bioRxiv2025

Stony coral tissue loss disease (SCTLD) destabilizes the coral microbiome

Stony coral tissue loss disease (SCTLD) is a rapidly spreading lethal coral disease, the etiology of which remains poorly understood. In this study, using deep metagenomic sequencing, we investigate microbial and viral community dynamics associated with SCTLD progression in the Caribbean stony coral Diploria labyrinthiformis. We assembled 264 metagenome-assembled genomes (MAGs) and correlated their abundance with disease phenotypes, revealing significant shifts in both the prokaryotic microbiome and virome. Our results provide clear evidence of microbial destabilization in diseased corals, suggesting that microbial dysbiosis is an outcome of SCTLD progression. We identified DNA viruses that increase in abundance in infected corals and are present in SCTLD-affected corals at other sites. In addition, we identify the first putative instance of asymptomatic/resistant SCTLD-affected colonies, suggesting potential microbial induced resilience (i.e., beneficial microbiome). Finally, we propose a mechanistic model of SCTLD progression, in which viral dynamics may contribute to a microbiome collapse. These findings provide novel insights into SCTLD pathogenesis and offer consistent molecular signals of disease across diverse geographic sites, presenting new opportunities for disease monitoring and mitigation.

microbiology↗

bioRxiv2025

WNT signaling in human pluripotent stem cells promotes HDAC2-dependent epigenetic programs and development of retinoic acid-responsive mesoderm

Human pluripotent stem cells (hPSCs) can be used as a scalable source of lymphocytes for adoptive cell therapies, contingent on the robust generation of definitive hematopoietic intermediates. Early WNT activation with CHIR99021 during mesoderm induction promoted the formation of KDR+ ALDH1A2+ mesodermal progenitors and subsequent generation of T cells in a retinoic acid (RA)-dependent manner. Integrated scRNA-seq and ATAC-seq defined a WNT-dependent developmental trajectory from hPSCs to KDR+ ALDH1A2+ mesoderm. Gene regulatory network modeling predicted HDAC2 and E-box transcription factors as regulators of RA-responsive mesodermal differentiation downstream of WNT. HDAC2 knockout impaired, while HDAC2 overexpression enhanced, KDR+ ALDH1A2+ progenitor formation. E-box factor manipulation had no discernible effect. An orthogonal chemical screen confirmed that HDAC2 inhibition suppressed KDR+ ALDH1A2+ mesodermal progenitors, whereas modulating histone methylation enhanced their formation. These findings reveal mechanisms by which WNT signaling promotes RA-responsive mesoderm and suggest methods to improve the generation of lymphocytes from hPSCs.

developmental biology↗

bioRxiv2025

Metaproteome analysis of the coral holobiont demonstrates algal symbiont dampening under thermal stress

The accelerating loss of coral reefs worldwide due to anthropogenic climate change has led to a myriad of studies aimed at understanding the basis of coral resilience to support reef conservation. Here, we integrate physiological measurements with proteomic and metabolomic profiles to examine species-specific responses to increased temperature in three sympatric reef-building corals from the Great Barrier Reef: Acropora hyacinthus, Porites lobata, and Stylophora pistillata. We find species-specific stress response strategies with A. hyacinthus, a thermally sensitive species, exhibiting rapid decline in endosymbiont physiology, coupled with a one-third reduction in protein abundance. In contrast, P. lobata displayed a delayed physiological response to stress and a muted proteome response, suggesting greater resilience. S. pistillata initially showed minor shifts in the proteome followed by colony "bail-out". Overall, we observed markedly different responses in most biochemical pathways in the three coral species. Nonetheless, some known biomarkers of stress, including heat-shock proteins, showed conserved responses to thermal stress with differences in temporal abundance reflecting bleaching resistance. Our results underscore the species-specific nature of coral responses to thermal stress and highlight proteomic signatures associated with symbiosis breakdown, offering mechanistic insights into coral bleaching susceptibility and resilience.

microbiology↗

bioRxiv2025

A genome wide CRISPR screen reveals novel determinants of long-lived plasma cell secretory capacity

Plasma cell subsets vary in their lifespans and ability to sustain humoral immunity. We conducted a genome-wide CRISPR-Cas9 screen in myeloma cells for factors that promote surface expression of CD98, a marker of longevity in mouse plasma cells. A large fraction of genes found to promote CD98 expression in this screen are involved in secretory and other vesicles, including subunits of the V-type ATPase complex. Genetic ablation and chemical inhibition of V-type ATPases in myeloma cells and primary plasma cells, respectively, reduced antibody secretion. Mouse and human long-lived plasma cells had greater numbers of acidified vesicles than their short-lived counterparts, and this correlated with increased antibody secretory capacity. The screen also revealed a requirement for the signaling adapter MYD88 in CD98 expression. Plasma cell-specific deletion of Myd88 led to reduced survival and antibody secretion by antigen-specific cells in vivo and unresponsiveness to BAFF and APRIL ex vivo. These data reveal novel regulators that link plasma cell secretory capacity and lifespan. SummaryLong-lived plasma cells rely on V-type ATPases, PI4K, DDX3X, and MYD88 signals for maximal secretory capacity and survival

immunology↗

bioRxiv2025

To pack or not to pack: revisiting protein side-chain packing in the post-AlphaFold era

MotivationProtein side-chain packing (PSCP), the problem of predicting side-chain conformation given a fixed backbone structure, has important implications in modeling of structures and interactions. However, despite the groundbreaking progress in protein structure prediction pioneered by AlphaFold, the existing PSCP methods still rely on experimental inputs, and do not leverage AlphaFold-predicted backbone coordinates to enable PSCP at scale. ResultsHere, we perform a large-scale benchmarking of the predictive performance of various PSCP methods on public datasets from multiple rounds of the Critical Assessment of Structure Prediction (CASP) challenges using a diverse set of evaluation metrics. Empirical results demonstrate that the PSCP methods perform well in packing the side-chains with experimental inputs, but they fail to generalize in repacking AlphaFold-generated structures. We additionally explore the effectiveness of leveraging the self-assessment confidence scores from AlphaFold by implementing a backbone confidence-aware integrative approach. While such a protocol often leads to performance improvement by attaining modest yet statistically significant accuracy gains over the AlphaFold baseline, it does not yield consistent and pronounced improvements. Our study highlights the recent advances and remaining challenges in PSCP in the post-AlphaFold era. AvailabilityThe code and raw data are freely available at https://github.com/Bhattacharya-Lab/PackBench.

bioinformatics↗

bioRxiv2025

RNAbpFlow: Base pair-augmented SE(3)-flow matching for conditional RNA 3D structure generation

Despite the groundbreaking advances in deep learning-enabled methods for biomolecular modeling, predicting accurate three-dimensional (3D) structures of RNA remains challenging due to the highly flexible nature of RNA molecules combined with the limited availability of evolutionary sequences or structural homology. Here we introduce RNAbpFlow, a novel sequence- and base-pair-conditioned SE(3)-equivariant flow matching model for generating RNA 3D structural ensemble. Leveraging a nucleobase center representation, RNAbpFlow enables end-to-end generation of all-atom RNA structures without the explicit or implicit use of evolutionary information or homologous structural templates. Experimental results show that base pairing conditioning leads to broadly generalizable performance improvements over current approaches for RNA topology sampling and predictive modeling in large-scale benchmarking. RNAbpFlow is freely available at https://github.com/Bhattacharya-Lab/RNAbpFlow.

bioinformatics↗

bioRxiv2024

THE FAM53C/DYRK1A axis regulates the G1/S transition of the cell cycle

A growing number of therapies are being developed to target the cell cycle machinery for the treatment of cancer and other human diseases. Consequently, a greater understanding of the factors regulating cell cycle progression becomes essential to help enhance the response to these new therapies. Here, using data from the Cancer Dependency Map, we identified FAM53C as a new regulator of cell cycle progression. We found that FAM53C is critical for this cell cycle transition and that it acts upstream of the CyclinD-CDK4/6-RB axis and of p53 in the regulation of the G1/S transition. By mass spectrometry, biochemical, and cellular assays, we identified and validated DYRK1A as a cell cycle kinase that is inhibited by and directly interacts with FAM53C. Consistent with the role for FAM53C identified in cells in culture, FAM53C knockout human cortical organoids display increased cell cycle arrest and growth defects. Fam53C knockout mice show minor behavioral phenotypes. Because DYRK1A dysregulation contributes to developmental disorders such as Down syndrome as well as tumorigenesis, future strategies aiming at regulating FAM53C activity may benefit a broad range of patients.

cell biology↗

bioRxiv2024

NEFFy: A Versatile Tool for Computing the Number of Effective Sequences

SummaryA Multiple Sequence Alignment (MSA) contains fundamental evolutionary information that is useful in the prediction of structure and function of proteins and nucleic acids. The "Number of Effective Sequences" (NEFF) quantifies the diversity of sequences of an MSA. Several tools can compute the NEFF of an MSA, each offering various options. NEFFy is the first software package to integrate all these options and calculate NEFF across diverse MSA formats for proteins, RNAs, and DNAs. It surpasses existing tools in functionality without compromising computational efficiency and scalability. NEFFy also offers per-residue NEFF calculation and supports NEFF computation for MSAs of multimeric proteins, with the capability to be extended to nucleic acids (DNA and RNA). Availability and ImplementationNEFFy is released as open-source software under the GNU General Public License v3.0. The source code in C++ and a Python wrapper are available on GitHub at https://github.com/Maryam-Haghani/NEFFy. To ensure users can fully leverage these capabilities, comprehensive documentation and examples are provided at https://Maryam-Haghani.github.io/NEFFy

bioinformatics↗

bioRxiv2024

RNF20-mediated H2B monoubiquitination protects stalled forks and promotes fork restart

Chromatin modifications play an important role in transcription, DNA replication and repair. Nonetheless, whether histone modifications regulate replication stress responses remains obscure. Here, we show that RNF20 localizes to and promotes H2B monoubiquitination (H2Bub) at replicating sites. Knockdown of RNF20 leads to degradation of stalled forks by MRE11 nuclease, which can be rescued by inhibition of MRE11 and co-depletion of SMARCAL1/HLTF/ZRANB3 fork remodelers. RNF20 facilitates the loading of RAD51 and RAD51C at the stalled fork sites and participates in the same pathway of RAD51/RAD51C-mediated fork protection and restart. Analyses with the RING domain and phosphorylation-deficient mutants of RNF20 showed that its catalytic activity and ATR/ATM-mediated phosphorylation are essential for its role in replication stress responses. Notably, treatment of RNF20-depleted cells with chromatin relaxing agents rescue the fork protection and restart defects. Collectively, our studies uncover the role of RNF20-mediated H2Bub in regulating the chromatin dynamics to safeguard the replicating genomes.

molecular biology↗

bioRxiv2024

Transcriptional landscape of the archaeal cell cycle is broadly conserved in eukaryotes

The cell cycle is a series of events that occur from the moment of cell birth to cell division. In eukaryotes, cell growth, genome replication, genome segregation, and cytokinesis are strictly coordinated, defining discrete cell cycle phases. In contrast, these key processes may occur concurrently in bacteria. Thermoacidophilic archaea in the genus Saccharolobus follow a defined cell cycle program, with the first pre-replicative growth (G1) phase, followed by the chromosome replication (S) phase, the second growth (G2) phase, and rapid genome segregation (M) and cytokinesis (D) phases. However, whether other processes, such as metabolism, catabolism, protein translation, and antiviral defense also occur at specific cell cycle phases, as in eukaryotes, or are active throughout the cell cycle, as in bacteria, remains unclear. To address this question, we synchronized cultures of S. islandicus and performed an in-depth transcriptomic analysis of samples enriched in cells undergoing the M-G1, S, and G2 phases. Differential gene expression and consensus gene co-expression network analyses provided a holistic view of the S. islandicus cell cycle. In addition to the core transcriptome network, which is expressed throughout the cell cycle, we show that diverse metabolic pathways, protein synthesis, cell motility and even antiviral defense systems, are expressed in a cell cycle dependent fashion. Our data also refines understanding of the processes previously known to be linked to the cell cycle, such as DNA replication. We show that most DNA replication genes are expressed prior to the S phase, during the M-G1, whereas expression of the major chromatin genes, and accordingly, chromatinization are concomitant with replication. A statistical model was used to define sets of signature genes characteristic of each of the analyzed cell cycle phases, emphasizing transcriptional stratification of the phases. Signature genes are more conserved across Thermoproteota than non-signature genes and their peak expression, especially for the M-G1 and G2 specific genes, matches that of homologs in yeast. Collectively, our data elucidate the complexity of the S. islandicus cell cycle and suggest that it more closely resembles the cell cycle of eukaryotes than previously appreciated.

microbiology↗

bioRxiv2024

Community-wide interactions sustain life in geothermal spring habitats

We investigated an alga-dominated geothermal spring community in Yellowstone National Park, USA. Our goal was to determine how cells cope with abiotic stressors during diurnal sampling that spanned over two orders of magnitude in solar irradiance. We report a community level response to toxic metal resistance and energy cycling that spans the three domains of life. Arsenic detoxification is accomplished via complementary gene expression by different lineages. Photosynthesis is dominated by Cyanidioschyzon, with the mixotroph, Galdieria, relegated to nighttime heterotrophy. Many key functions, including the cell cycle, are strongly regulated by diurnal light fluctuations. These results demonstrate that biotic interactions are highly structured in extreme habitats. We suggest this was also the case on the early Earth when geothermal springs were cradles of microbial life, prior to the origin of eukaryotes.

evolutionary biology↗

bioRxiv2024

Single-sequence protein-RNA complex structure prediction by geometric attention-enabled pairing of biological language models

Ground-breaking progress has been made in structure prediction of biomolecular assemblies, including the recent breakthrough of AlphaFold 3. However, it remains challenging for AlphaFold 3 and other state-of-the-art deep learning-based methods to accurately predict protein-RNA complex structures, in part due to the limited availability of evolutionary and structural information related to protein-RNA interactions that are used as inputs to the existing approaches. Here, we introduce ProRNA3D-single, a new deep-learning framework for protein-RNA complex structure prediction with only single-sequence input. Using a novel geometric attention-enabled pairing of biological language models of protein and RNA, a previously unexplored avenue, ProRNA3D-single enables the prediction of interatomic protein-RNA interaction maps, which are then transformed into multi-scale geometric restraints for modeling 3D structures of protein-RNA complexes via geometry optimization. Benchmark tests show that ProRNA3D-single convincingly outperforms current state-of-the-art methods including AlphaFold 3, particularly when evolutionary information is limited; and exhibits remarkable robustness and performance resilience by attaining better accuracy with only single-sequence input than what most methods can achieve even with explicit evolutionary information. Freely available at https://github.com/Bhattacharya-Lab/ProRNA3D-single, ProRNA3D-single should be broadly useful for modeling 3D structures of protein-RNA complexes at scale, regardless of the availability of evolutionary information.

bioinformatics↗

bioRxiv2024

GpsB is an accessory Z-ring anchor

Bacterial cytokinesis is a well-coordinated process in which multiple proteins, collectively called the divisome, are recruited to the site of division. A key member of the divisome is FtsZ which forms a ring-like structure (Z-ring) to mark the division site through its association with Z-ring anchors. Synchronized movement of Z-ring filaments and peptidoglycan synthesis along the axis of division help generate a division septum to separate the daughter cells. Thus, FtsZ needs to be linked to the PG synthesis machinery. GpsB is a highly conserved protein among the members of the Firmicutes phylum which has been shown to regulate cell wall synthesis through interaction with penicillin binding proteins. Previously published data from our lab established GpsB as a member of the divisome which directly interacts with FtsZ in Staphylococcus aureus. More specifically, we showed that GpsB binds to FtsZ by recognizing the R-X-X-R sequence in its C- terminal tail (CTT) region. As the GpsB recognition sequence is also present in Bacillus subtilis, we speculated that GpsB-FtsZ interaction might occur in this organism as well. In support of our prediction, previous studies reported that disruption of gpsB and ezrA or gpsB and ftsA is deleterious. Given that both EzrA and FtsA are known Z-ring anchors, we hypothesized that in the absence of other FtsZ anchors, GpsB can fulfill this role in B. subtilis. Our data, taken together, conclusively shows that GpsB is a Z-ring anchor in B. subtilis and this role of GpsB only becomes apparent in the absence of other FtsZ anchoring proteins. Based on the conserved nature of the R-X-X-R sequence in FtsZ- CTT, we also tested GpsB-FtsZ interaction in Enterococcus faecalis and Listeria monocytogenes and show that this recognition motif dependent interaction is present in the former but not the latter. Our results suggest the possibility of C-terminal R-X-X-R independent interaction in L. monocytogenes and Streptococcus pneumoniae. Thus, it appears that GpsB may serve as an accessory Z-ring anchor in multiple organisms. ImportanceCell division is essential for production of offsprings and propagation of life. In bacteria, a key tubulin-like cell division protein FtsZ is brought to the division site by the action of multiple regulators. Arrival of FtsZ and activation of cell wall synthesis are needed to build a division septum to separate the daughter cells. As such, this vital process is controlled by redundant fail-safe mechanisms. For instance, multiple proteins can anchor FtsZ to the membrane at the division site. In this report, we reveal that yet another protein, GpsB, could serve as a back-up FtsZ anchor. GpsB is normally associated with cell wall synthesis in most organisms of the Firmicutes phylum. However, in the absence of other known dedicated FtsZ anchoring factors, GpsB is able to step in to rescue cell division. We provide evidence that this GpsB-FtsZ interaction is present in Staphylococcus aureus, Bacillus subtilis, Enterococcus faecalis, Listeria monocytogenes, and possibly Streptococcus pneumoniae. As the rapid rise in antibiotic resistance is threatening public health globally, knowledge of unique important cell division factors could be harnessed to develop new antibacterial therapeutics.

microbiology↗