Biology subjects

Islam, S. T.

Publications and source records attributed to Islam, S. T..

10 recordsLinked to original sources

bioRxiv2026

Biosurfactant polysaccharide drives dispersal of exopolysaccharide-coated myxospores in Myxococcus xanthus

Bacterial spores are highly resilient cell forms, yet the organization of their protective surface layers in diderm species remains largely unexplored. For the social predatory soil bacterium Myxococcus xanthus, myxospore formation within multicellular fruiting body structures is a key ecological adaptation to surviving conditions of nutrient deprivation. These myxospores were long thought to be outwardly coated with so-called major spore coat (MASC) polysaccharide. Using polysaccharide-deficient mutant strains, electron microscopy, surface hydrophobicity assays, dye binding, and functional swarm complementation, we show that MASC instead forms a protective sub-surface outer-cortex layer, while the exopolysaccharide (EPS) glycocalyx inherited from vegetative cells constitutes the true outermost myxospore coat. EPS mediates inter-myxospore adhesion and supports collective behaviors, whereas secretion of biosurfactant polysaccharide (BPS) reduces myxospore surface stickiness, preventing excessive aggregation. BPS-deficient myxospores form persistent clumps, while EPS-deficient myxospores fail to aggregate or restore EPS-dependent swarm motility of vegetative cells. These results reveal a mechanistic interplay in which MASC serves as a sub-surface protective layer, EPS defines the exterior interface, and BPS tunes surface accessibility to regulate dispersal. Our findings overturn long-standing assumptions about myxospore architecture and illustrate a polysaccharide-driven strategy for controlling aggregation and readiness for germination. More broadly, these results highlight how social diderm bacteria leverage inherited and dynamically remodeled polysaccharide surfaces to coordinate multicellular development, in contrast to the rigid protein-based spore surfaces of Gram-positive species.

microbiology↗

bioRxiv2026

Isoflurane and surgery aggravate APOE4-dependent lipid dysregulation and neural dysfunction, leading to neurological impairment in male mice

PurposePerioperative exposure to the volatile anesthetic isoflurane (ISO) has been associated with cognitive and olfactory deficits and may increase the risk of Alzheimers disease (AD). Apolipoprotein E4 (APOE4), the strongest genetic risk factor for AD, contributes to disease pathogenesis through disrupted lipid homeostasis. However, whether and how isoflurane interacts with APOE genotype to influence neurological vulnerability remains unclear. MethodsYoung adult, presymptomatic humanized APOE4 and APOE3 knock-in mice underwent laparotomy under 2 h of isoflurane anesthesia. Microglia and astrocytes were isolated from the olfactory bulb (OB) and hippocampus (HI) by magnetic-activated cell sorting. Lipid composition, transcriptional responses, and functional outcomes were assessed using lipidomic, bulk RNA-seq, and longitudinal behavioral testing. In vivo and ex vivo electrophysiological recordings evaluated neuronal excitability and synaptic transmission in both regions. ResultsBy day 7 post-anesthesia, cell type-specific lipidomic profiling of both OB and HI revealed more pronounced lipid perturbations in microglia and astrocytes from APOE4/ISO mice than from APOE3 mice, characterized by elevated free fatty acids, increased lipid peroxidation, triglyceride depletion, and reduced hippocampal hexosylceramides and cardiolipins. Electrophysiological recordings showed greater olfactory circuit dysfunction in APOE4/ISO mice, accompanied by persistent odor memory deficits, transient olfactory sensitivity loss, early motor coordination impairments, and delayed cognitive deficits. RNA sequencing of the OB identified downregulated lipid metabolism and atherosclerosis-related pathways. ConclusionThese findings establish a mechanistic link between APOE4-dependent glial lipid dysregulation, olfactory circuit dysfunction, and delayed cognitive impairment following isoflurane anesthesia and surgery, highlighting lipid homeostasis as a potential therapeutic target.

neuroscience↗

bioRxiv2026

In vitro investigation and evaluation of the antidiabetic potential of the ethanolic extract of Asparagus racemosus using starch digestion, glucose diffusion, glucose uptake, and DPPH assays

Asparagus racemosus commonly known as Shatamull, is a medicinal plant with pharmacological applications documented in both Indian and British Pharmacopoeias and various traditional medicinal practices. Previous studies have reported that A. racemosus reduces hyperglycemia by enhancing insulin secretion. The aim of the current study was to assess the antihyperglycemic actions and explore the underlying mechanisms of action of A. racemosus utilizing in vitro carbohydrate digestion, glucose diffusion, glucose uptake, 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and preliminary phytochemical screening. The inhibition of carbohydrate digestion was assessed using -amylase and -glucosidase enzyme assays. The effect on glucose diffusion was evaluated using cellulose ester dialysis tube. Subsequently, glucose uptake was measured in a yeast cell model at different glucose concentrations, and the antioxidant potential was evaluated by measuring DPPH radical scavenging activity. A. racemosus significantly reduced (p<0.05- 0.01) glucose release during in vitro starch digestion by 21.11%, whereas glucose absorption decreased by 22.75% (p<0.05-0.001). The most significant enhancement (p<0.05-0.001) in glucose uptake by 65.03%, was observed at 5 mM glucose concentration. Furthermore, it showed significant antioxidant activity by scavenging DPPH (p<0.05, 0.001) radicals by 42.46%. Preliminary phytoconstituent screening indicated the existence of flavonoids, tannins, steroids, glycosides and saponins. In conclusion, A. racemosus shows an inhibitory effect on carbohydrate digestion and absorption, enhances glucose uptake and demonstrates significant DPPH radical scavenging activity, potentially due to the presence of naturally occurring phytochemicals. Thus, A. racemosus may contribute as a promising antidiabetic drug for the treatment of diabetes mellitus. More investigations are needed to determine the active compounds in A. racemosus that contribute to its antidiabetic effects.

pharmacology and toxicology↗

bioRxiv2023

Molecular dynamics of outer membrane-embedded polysaccharide secretion porins reveals closed resting-state surface gates targetable by virtual fragment screening for drug hotspot identification

Recent advances in iterative neural-network analyses (e.g. AlphaFold2 and RoseTTA fold) have been revolutionary for protein 3D-structure prediction, especially for difficult-to-manipulate -helical/{beta}-barrel integral membrane proteins. These model structures are calculated based on the co-evolution of amino acids within the protein of interest and similarities to existing protein structures; local effects of the membrane on folding and stability of the calculated model structures are not considered. We recently reported the discovery, 3D modelling, and characterization of 18-{beta}-stranded outer-membrane (OM) WzpX, WzpS, and WzpB {beta}-barrel secretion porins for the exopolysaccharide (EPS), major spore coat polysaccharide (MASC), and biosurfactant polysaccharide (BPS) pathways (respectively) in the Gram-negative social predatory bacterium Myxococcus xanthus DZ2. However, information was not obtained regarding the dynamic behavior of surface-gating WzpX/S/B loop domains, nor on potential treatments to inactivate these porins. Herein, we developed a molecular dynamics (MD) protocol to study the core stability and loop dynamism of neural network-based integral membrane protein structure models embedded in an asymmetric OM bilayer, using the M. xanthus WzpX, WzpS, and WzpB proteins as test candidates. This was accomplished through integration of the CHARMM-graphical user interface (GUI) and Molecular Operating Environment (MOE) workflows to allow for rapid simulation system setup and facilitate data analysis. In addition to serving as a method of model-structure validation, our molecular dynamics simulations revealed minimal movement of extracellular WzpX/S/B loops in the absence of an external stimulus, as well as druggable cavities between the loops. Virtual screening of a commercial fragment library against these cavities revealed putative fragment-binding hotspots on the cell-surface face of each {beta}-barrel, along with key interacting residues, and identified promising hits for the design of potential binders capable of plugging the {beta}-barrels and inhibiting polysaccharide secretion.

molecular biology↗

bioRxiv2023

Integrin-like adhesin CglD confers traction and stabilizes bacterial focal adhesions involved in myxobacterial gliding motility

AO_SCPLOWBSTRACTC_SCPLOWIntegrins are crucial for eukaryotic cell attachment and motility within the extracellular matrix (ECM) via focal-adhesion formation, with their evolutionary emergence important for the development of multicellularity. Intriguingly, single gliding cells of the predatory deltaproteobacterium Myxococcus xanthus form bacterial focal-adhesion (bFA) sites; therein, helically-trafficked motors become immobilized at anchored locations through Glt apparatus association with cell-surface integrin I-domain-like adhesin CglB. Using traction-force, bead-force, and total internal reflection-fluorescence microscopies combined with biochemical approaches, we herein identify the von Willebrand A domain-containing cell-surface lipoprotein CglD to be a {beta}-integrin-like outer-membrane lipoprotein that functionally associates with and anchors the trans-envelope Glt-CglB gliding apparatus, stabilizing and efficiently anchoring this assembly at bFAs. Calcium dependence governs CglD importance, consistent with its integrated ECM eukaryotic cartilage oligomeric matrix protein domains. CglD thus confers mechanosensory and mechanotransductory capabilities to the gliding apparatus, helping explain bFA-mediated trans-envelope force transduction, from inner-membrane-embedded motors to the cell surface.

microbiology↗

bioRxiv2022

Bacterial outer-membrane polysaccharide export (OPX) proteins occupy three structural classes with selective β-barrel porin requirements for polymer secretion

Secretion of high-molecular-weight polysaccharides across the bacterial envelope is ubiquitous as it enhances prokaryotic survival in (a)biotic settings. Such polymers are often assembled by Wzx/Wzy- or ABC transporter-dependent schemes that implicate outer-membrane (OM) polysaccharide export (OPX) proteins in polymer translocation to the cell surface. In the social predatory bacterium Myxococcus xanthus, exopolysaccharide (EPS)-pathway WzaX, major spore coat (MASC)-pathway WzaS, and biosurfactant polysaccharide-pathway WzaB were herein found to be truncated OPX homologues of Escherichia coli Wza lacking OM-spanning -helices. Comparative genomics across all bacteria, complemented with cryo-electron tomography cell- envelope analyses, revealed WzaX/S/B architecture to be the most common amongst three defined OPX-protein structural classes independent of periplasmic thickness. Fold-recognition and deep- learning analyses revealed the conserved M. xanthus proteins MXAN_7418/3226/1916 (encoded adjacent to WzaX/S/B) to be integral OM {beta}-barrels, with structural homology to the poly-N-acetyl-D- glucosamine synthase-dependent pathway porin PgaA. Such porins were identified in bacteria near numerous genes for all three OPX-protein classes. Interior MXAN_7418/3226/1916 {beta}-barrel electrostatics were found to match known properties of their associated polymers. With MXAN_3226 essential for MASC export, and MXAN_7418 absence shown herein to compromise EPS translocation, these data support a novel secretion paradigm for Wzx/Wzy-dependent pathways in which those containing an OPX component that cannot span the OM instead utilize a {beta}-barrel porin to mediate polysaccharide transport across the OM.

microbiology↗

bioRxiv2020

Bacterial glycocalyx integrity drives multicellular swarm biofilm dynamism

Bacterial surface exopolysaccharide (EPS) layers are key determinants of biofilm establishment and maintenance, leading to the formation of higher-order 3D structures conferring numerous survival benefits to a cell community. In addition to a specific EPS glycocalyx, we recently revealed that the social {delta}-proteobacterium Myxococcus xanthus secretes a novel biosurfactant polysaccharide (BPS), with both EPS and BPS polymers required for type IV pilus (T4P)-dependent swarm expansion via spatio-specific biofilm expression profiles. Thus the synergy between EPS and BPS secretion somehow modulates the multicellular lifecycle of M. xanthus. Herein, we demonstrate that BPS secretion functionally-activates the EPS glycocalyx via its destabilization, fundamentally altering the characteristics of the cell surface. This impacts motility behaviours at the single-cell level as well as the aggregative capacity of cells in groups via EPS fibril formation and T4P assembly. These changes modulate structuration of swarm biofilms via cell layering, likely contributing to the formation of internal swarm polysaccharide architecture. Together, these data reveal the manner by which the interplay between two secreted polymers induces single-cell changes that modulate swarm biofilm communities.

microbiology↗

bioRxiv2020

CglB adhesins secreted at bacterial focal adhesions mediate gliding motility

AO_SCPLOWBSTRACTC_SCPLOWThe predatory deltaproteobacterium Myxococcus xanthus uses a helically-trafficked motor at bacterial focal adhesion (bFA) sites to power gliding motility. Using TIRF and force microscopy, we herein identify the integrin I-domain-like outer-membrane (OM) lipoprotein CglB as an essential substratum-coupling protein of the gliding motility complex. Similar to most known OM lipoproteins, CglB is anchored on the periplasmic side of the OM and thus a mechanism must exist to secrete it to the cell surface in order for it to interact with the underlying substratum. We reveal this process to be mediated by a predicted OM {beta}-barrel structure of the gliding complex. This OM platform was found to regulate the conformational activation and secretion of CglB across the OM. These data suggest that the gliding complex promotes surface exposure of CglB at bFAs, thus explaining the manner by which forces exerted by inner-membrane motors are transduced across the cell envelope to the substratum; they also uncover a novel protein secretion mechanism, highlighting the ubiquitous connection between secretion and bacterial motility.

microbiology↗

bioRxiv2020

Modulation of bacterial multicellularity via spatiotemporal polysaccharide secretion

AO_SCPLOWBSTRACTC_SCPLOWThe development of multicellularity is a key evolutionary transition allowing for differentiation of physiological functions across a cell population that confers survival benefits; among unicellular bacteria, this can lead to complex developmental behaviours and the formation of higher-order community structures. Herein, we demonstrate that in the social {delta}-proteobacterium Myxococcus xanthus, the secretion of a novel secreted biosurfactant polysaccharide (BPS) is temporally and spatially modulated within communities, mediating swarm migration as well as the formation of multicellular swarm biofilms and fruiting bodies. BPS is a type IV pilus-inhibited acidic polymer built of randomly-acetylated {beta}-linked tetrasaccharide repeats. Both BPS and the "shared good" EPS are produced by dedicated Wzx/Wzy-dependent polysaccharide assembly pathways distinct from that responsible for spore coat assembly. To our knowledge, such pathways have never-before been explicitly shown to synthesize a biosurfactant. Together, these data reveal the central role of secreted polysaccharides in the intricate behaviours coordinating bacterial multicellularity.

microbiology↗

bioRxiv2019

Chitosan films for microfluidic studies of single bacteria and perspectives for antibiotics susceptibility testing

Single cell microfluidics is powerful to study bacteria and determine their susceptibility to antibiotics treatment. Glass treatment by adhesive molecules is a potential solution to immobilize bacterial cells and perform microscopy but traditional cationic polymers such as poly-lysine deeply affect bacterial physiology. In this work, we chemically characterized a class of chitosan polymers for their biocompatibility when adsorbed to glass. Chitosan chains of known length and composition allowed growth of Escherichia coli cells without any deleterious effects on cell physiology. Combined with a machine-learning approach, this method could measure the antibiotics susceptibility of a diversity of clinical strains in less than 1 hour and with higher accuracy than current methods. Last, chitosan polymers also supported growth of Klebsiella pneumoniae, another bacterial pathogen of clinical significance. The low cost of chitosan slides and their simple implementation makes them highly versatile for research as well as clinical use.

microbiology↗