Biology subjects

Mahajan, S.

Publications and source records attributed to Mahajan, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Targeting TMPRSS2-ERG Fusion-Driven Prostate Cancer using Novel HBS-α-Helicomimics

Gene fusions between the androgen receptor (AR)-responsive gene TMPRSS2 and ERG occur in approximately 50% of prostate cancers (PCa), thereby promoting tumorigenesis through aberrant ERG expression. Therapeutic targeting of transcription factor-DNA interfaces remains a formidable challenge, largely owing to the entropic penalty associated with peptide folding during target engagement. Here, we describe the structure-guided design and preclinical evaluation of hydrogen-bond surrogate (HBS)-constrained alpha-helicomimics targeting the ERG-DNA recognition interface. Structural analysis of ERG-DNA complex revealed that DNA binding induces elongation of recognition helix H4 from approximately 2.5 to 4.0 helical turns. To stabilize the bioactive conformation, we incorporated an N-terminal HBS macrocycle, introduced D363E and S366E mutations to enhance DNA binding and structural stability, and added dual NLS-TAT tags to facilitate cellular delivery. Biochemical and cellular assays demonstrated that the lead compound, ERG helicomimics, competitively inhibited ERG binding to ETS motifs, disrupted ERG association with AR and other cofactors, leading to suppressed ERG transcriptional activity. Chromatin immunoprecipitation-qPCR confirmed reduced ERG occupancy at regulatory regions of canonical target genes, accompanied by downregulation of ERG-driven transcriptional programs. ERG helicomimics also reduced proliferation, migration, and invasion in ERG-positive PCa cells. In a murine xenograft model of TMPRSS2-ERG-positive PCa, systemic ERG helicomimics treatment suppressed tumor growth without overt toxicity and reduced Ki-67 expression compared with the designated control peptide. Collectively, our findings support HBS-constrained ERG helicomimics as a rational strategy for targeting ERG-driven PCa and warrant further therapeutic optimization.

cancer biology↗

bioRxiv2026

Limited Volumetric Separation Across CDR Groups in OASIS-1

Clinical Dementia Rating (CDR) scores are used to classify the cognitive state of patients and are provided within neuroimaging datasets. This is achieved through a standardized clinical assessment that evaluates participants cognitive and functional abilities in everyday life, after which they are given a score ranging from 0 to 3. Where 0 represents no signs of dementia and three represents severe dementia1. These scores are then used to track the progression of dementia over time2. This study explored if these CDR labels within the OASIS-1 dataset produced consistent volumetric separation across the hippocampus, amygdala, and cortex.

neuroscience↗

bioRxiv2026

Repetition-controllable gain-managed nonlinear fiber amplifier enables ultrashort, multiphoton imaging with reduced photodamage

1.We report a repetition-controllable gain-managed nonlinear fiber amplifier (GMNA) that delivers near-infrared 50-fs pulses with pulse energies up to 150 nJ and a widely tunable repetition rate from 1-20 MHz, while maintaining stable pulse quality across the full range. Using this source, we demonstrate label-free multiphoton imaging--including metabolic autofluorescence (2PF/3PF), second/third-harmonic generation, and Simultaneous Label-free Autofluorescence Multiharmonic (SLAM) microscopy imaging--across live cells, human lung spheroids, and hard tissues. We further assess the impact of laser repetition rate on photodamage at fixed pulse energy, supported by preliminary measurements indicating lower damage at lower repetition rate. Collectively, the compact architecture and repetition-rate agility of the GMNA enable real-time optimization of imaging speed, depth, and sample safety for advanced biological microscopy.

biophysics↗

bioRxiv2026

Patient iPSC-Derived Cartilage Organoids Reveal Defective ECM Deposition and Altered Chondrogenic Trajectory in Saul-Wilson Syndrome

Saul-Wilson syndrome (SWS) is a skeletal dysplasia characterized by primordial dwarfism and progeroid features caused by a recurrent dominant COG4 variant (p.G516R). We previously showed that this mutation accelerates Golgi retrograde trafficking and disrupts glycosylation of the proteoglycan decorin, while zebrafish models revealed defects in chondrocyte elongation and intercalation. We have also shown that the SW1353 chondrosarcoma cells carrying the SWS variant exhibit reduced secretion of extracellular matrix (ECM) components. While these results indicate a critical function of COG4 in Golgi processing, the developmental process leading to skeletal dysplasia in SWS patients remains unknown. Here, we generated patient-derived iPSC cartilage organoids (SWS organoids), modeling early human chondrogenesis. SWS organoids failed to produce cartilage structures and displayed poor expression of chondrogenic markers. Time-course RNA-seq analysis of the chondrogenic process revealed reduced activation of gene networks involved in skeletal development, ECM organization, ossification, and glycosaminoglycan metabolism. Spatial multiomic analysis of protein and glycosylation by CODEX and GLYPH imaging revealed an altered chondrogenic trajectory, persistence of mesenchymal states, global glycosylation changes, and reduced deposition of chondroitin sulfate proteoglycans. These results indicate that the COG4 mutation disrupts ECM glycosylation and chondrogenic commitment, and that SWS organoids model early defects in cartilage formation underlies impaired skeletal growth in SWS. HighlightsO_LIPatient iPSC-derived cartilage organoids model development defects in Saul-Wilson syndrome C_LIO_LISWS organoids show defective extracellular matrix deposition and attenuated chondrogenic gene expression C_LIO_LIGlycan profiling reveals global glycosylation defects and deficient proteoglycan GAG chains C_LIO_LIAn early developmental impairment in chondrogenesis alters skeletal formation in Saul-Wilson syndrome C_LI

developmental biology↗

bioRxiv2026

Structural basis of metalloid transport by the arsenite efflux pump ArsB

Bacteria resist toxic arsenite (AsIII) in their environments by actively pumping the metalloid out of the cell via efflux pumps such as ArsB. However, the mechanism of extrusion remains poorly understood, which hinders the development of engineered bioremediation strategies. We report high-resolution cryo-EM structures of ArsB from the arsenic-tolerant bacterium Leptospirillum ferriphilum. ArsB adopts an inverted two-fold repeat architecture resembling that of other ion transporter (IT) superfamily proteins. Structures determined in the presence of AsIII and antimonite (SbIII) reveal that the metalloid substrates interact with polar residues at the core of the transmembrane domain primarily via hydrogen bonding. Mutagenesis and in vivo functional assays support these interactions. Our ArsB structures represent an inward-facing conformation, where the metalloid-binding site is exposed to the cytoplasm, suitable for metalloid capture. Furthermore, we demonstrate that AsIII resistance conferred by ArsB varies with external pH, supporting that ArsB is a proton (H+)-coupled secondary transporter. Mutagenesis, in vivo functional assays, and pKa estimation imply that conserved aspartate residues near the metalloid-binding site likely mediate the H+-coupling mechanism. Our findings provide structural insights into metalloid recognition and H+/metalloid antiport in ArsB, laying a foundation for further elucidation of the molecular basis of toxic metalloid detoxification in bacteria.

biochemistry↗

bioRxiv2026

In vivo X-ray Computed Microtomography: A Novel Approach to Assess Coral Skeletal Construction

Scleractinian (stony) corals build reef frameworks through calcium carbonate deposition, yet all methods for assessing skeletal growth - staining, SEM, or ex vivo {micro}CT - are limited to endpoint measurements on dead specimens. Here, we utilise in vivo X-ray computed microtomography ({micro}CT) to non-destructively quantify skeletal growth in the reef-building coral Stylophora pistillata for the first time. Our in vivo {micro}CT approach applied to one individual over 16 days revealed a volume increase from [~]630 to [~]700 mm3 that can be partitioned into external vertical extension and internal lateral thickening, generating high-resolution 4D reconstructions of the evolving skeletal architecture. These measurements were consistent with established approaches but provide additional unique insights into internal growth dynamics. We demonstrate that in vivo CT enables micron-scale monitoring of calcification processes of living stony corals, thereby representing a powerful new tool to probe coral growth dynamics in the face of rapidly changing environmental conditions.

bioengineering↗

bioRxiv2025

Posterior Cortex Isolation Enhances Detection of Alpha Desynchronization During Sustained Attention

Electroencephalography (EEG) is an essential tool for assessing the neural activity behind mental fatigue, a factor that can influence both cognitive and physical performance. Mental fatigue influences alpha-band oscillations (8-12 Hz), reflecting cortical engagement and attention stability. In this study, EEG recordings from 109 participants in the Physionet open-source EEG Motor Movement/Imagery Dataset (EEGMMIDB) were analyzed to characterize alpha power changes during sustained attention. Spectral analysis was performed across early and late task blocks to quantify alpha desynchronization over time. Participants demonstrated a consistent decrease in alpha power ({Delta} = -0.076 {+/-} 0.019 log10 units; p = 0.0001), indicating desynchronization associated with sustained attentional demand. These findings show the applicability of open-source EEG datasets for research. Furthermore, these findings support the isolation of posterior activation as a marker of mental fatigue through alpha desynchronization. One sentence overviewAlpha desynchronization is a marker for mental fatigue in EEGs. This paper illustrates that isolating the posterior cortical lobes enhances the resolution and sensitivity of alpha band changes associated with sustained attention.

neuroscience↗

bioRxiv2025

EGFL7 promotes immune evasion in glioma through its interaction with integrin β2

Glioblastoma is the most aggressive form of malignant brain cancer, characterized by an immunosuppressive microenvironment and immune evasion. Despite the success of immune checkpoint inhibitors in other cancers, immunotherapies such as anti-PD1 have shown limited efficacy in glioblastoma, underscoring the need to identify tumor-intrinsic mechanisms that sustain this immunosuppressive microenvironment and to develop more effective therapeutic strategies targeting them. Previously, the secreted factor epidermal growth factor-like protein 7 (EGFL7) has been shown to promote brain tumor growth by affecting the glioblastoma microenvironment (GME). However, its impact on the immune system remained enigmatic. Here, we studied the role of EGFL7 in shaping the immune landscape in glioblastoma and identified the underlying molecular mechanisms it engages to drive glioma immune evasion. Single-cell transcriptomic profiling of immune cells derived of glioblastoma revealed that EGFL7 promotes an immunosuppressive GME, characterized by enhanced T cell exhaustion and polarization of macrophages towards a protumorigenic state. Proteomic profiling of EGFL7s interactome in glioma revealed its interaction with integrin {beta}2 (ITGB2), an immune cell surface receptor involved in cell adhesion and migration. Mechanistic studies uncovered the central role of this interaction for immune evasion, which promoted T cell exhaustion and the polarization of macrophages towards a pro-tumorigenic state. Genetic perturbation of the EGFL7-ITGB2 axis attenuated immunosuppression and prolonged the survival of glioblastoma-bearing mice. Remarkably, a combinatorial regimen of anti-EGFL7 and the checkpoint inhibitor anti-PD1 improved the efficacy of this drug, which by itself did not improve glioma patient survival so far. In conclusion, our study provides unequivocal evidence that EGFL7 mediates immune evasion in glioma and has great potential to serve as an add-on drug target to improve immunotherapies not functional in glioblastoma patients so far.

cancer biology↗

bioRxiv2025

Characterising Type I Collagen Architecture in Human Bone and Osteosarcoma with Second Harmonic Generation Microscopy

Aberrant collagen matrix production is a hallmark of many cancers, including osteosarcoma (OS), the most common primary cancer of bone which remains poorly diagnosed. Here, the phenotyping potential of second harmonic generation (SHG) microscopy has been demonstrated through label-free imaging of pathologically altered collagen matrices within clinical biopsies. This work examined SHG imaging in quantifying OS-specific collagen (type I) signatures - focused on fibre length-based parameters - across clinical biopsies. We describe a novel SHG analysis workflow, following systematic optimisation of image resolution and field of view (FOV) size to enable robust quantification of collagen fibre-length metrics in human bone and OS. This included analyses of SHG images with a FOV spanning 350 {micro}m x 350 {micro}m to 1400 {micro}m x 1400 {micro}m, with the latter enabling whole-biopsy visualisation via stitching of up to 64 regions. In normal cortical (rib) bone biopsies, average fibre lengths did not significantly differ across increasing FOV size (26.44 {+/-} 1.75 {micro}m, 26.34 {+/-} 2.01 {micro}m, 27.25 {+/-} 2.47 {micro}m, 28.78 {+/-} 3.58 {micro}m). However, analysis of the top 50th percentile of collagen fibres revealed significant differences between the smallest FOVs; 350 {micro}m x 350 {micro}m and 466 {micro}m x 466 {micro}m, versus the largest 1400 {micro}m x 1400 {micro}m (p = 0.03 and p = 0.04 respectively), highlighting the requirement for larger FOVs for optimal characterisation of human bone collagen. Comparison of normal bone and OS (stage IIB) biopsies, the largest FOV revealed the largest differences, with OS exhibiting significantly reduced collagen fibre lengths (female OS: 23.18 {+/-} 0.56 {micro}m vs. bone: 29.39 {+/-} 2.17 {micro}m, p < 0.001; male OS: 24.39 {+/-} 1.32 {micro}m vs. bone: 27.87 {+/-} 1.05 {micro}m, p = 0.02) versus normal bone. Subsequent analyses across OS stages (IB - IVB) showed further evidence of pathological collagen signatures amplified with OS progression. These findings demonstrate that SHG microscopy enables robust, quantitative phenotyping of human bone and osteosarcoma collagen matrices, offering new potential for improved diagnosis and disease staging.

cancer biology↗

bioRxiv2025

Single-Cell Metabolic Imaging Reveals Glycogen Driven-Adaptations in Endothelial Cells

Endothelial dysfunction (ED) is a defining feature of diabetes mellitus (DM) and a key contributor to many metabolic and cardiovascular diseases. Endothelial cells (ECs) are known to be highly glycolytic and primarily rely on glucose to meet their energy demands. However, the role of glycogen metabolism in ECs remains poorly characterized due to a lack of suitable tools. Here, we utilize stimulated Raman scattering (SRS) microscopy to investigate subcellular glycogen metabolism in live ECs under stress conditions associated with highly prevalent diabetes and diabetic complications. We demonstrate that ECs exposed to a diabetes-mimicking milieu- high glucose and tumor necrosis factor (TNF-)- divert excess glucose toward subcellular glycogen storage, and that this storage capacity is significantly enhanced by the inhibition of glycogen synthase kinase 3 (GSK3). Pulse-chase experiments uncover glycogen dynamics and reveal that glycogen is rapidly mobilized under glucose starvation, highlighting its role as an immediate energy reserve in ECs. We further extend the capabilities of SRS metabolic imaging to visualize glutamine and lactate metabolism for the first time, directly showcasing the reliance of ECs on these alternative carbon substrates during glucose deprivation. Our results indicate that ECs containing glycogen exhibit a reduced immediate metabolic demand for these gluconeogenic substrates in the absence of extracellular glucose. These findings suggest that glycogen may play a broader role beyond energy reserves in ECs by modulating stress-responsive metabolic adaptations and may offer potential therapeutic opportunities to address diabetes-induced ED and related cardiometabolic diseases.

cell biology↗

bioRxiv2025

Harnessing machine learning to predict antibiotic susceptibility in Pseudomonas aeruginosa biofilms

Standard antibiotic susceptibility tests (ASTs) often fail to accurately predict treatment outcomes because they do not account for biofilm-specific mechanisms of reduced susceptibility. In the present study, we explored alternative approaches to predict tobramycin susceptibility of Pseudomonas aeruginosa biofilms that were experimentally evolved in physiologically relevant conditions. To this end, we used four analytical methods - whole-genome sequencing (WGS), matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS), isothermal microcalorimetry (IMC) and multi-excitation Raman spectroscopy (MX-Raman). Machine learning models were trained on data outputs from these methods to predict tobramycin susceptibility of our evolved strains and subsequently validated with a collection of clinical isolates. For minimal inhibitory concentration (MIC) predictions of the evolved strains, the highest accuracy{+/-}1 was achieved with MALDI-TOF MS (97.83 %), while for biofilm prevention concentration (BPC) predictions, Raman spectroscopy performed best with an accuracy{+/-}1 of 80.43 %. Overall, all analytical methods demonstrated comparable predictive performance, showing their potential for improving biofilm AST.

microbiology↗

bioRxiv2025

Chromosome-level genome assembly of Tamarindus indica

Tamarindus indica is the sole member of the genus Tamarindus of the Leguminosae family. It is a multipurpose horticultural plant, with every part of the plant finding importance in food, medicine, and other industries. To gain an understanding of genome structure and evolution, we reported the first high-quality genome assembly of T. indica anchored to 12 chromosomes with N50 of [~]56 Mb. Supported by comprehensive transcriptome data, we reported >48,000 protein-coding genes. Through phylogenetic and evolutionary analysis, we uncovered an independent whole-genome duplication event in T. indica and highlighted the expression divergence of segmentally duplicated genes and their role in the better adaptivity of the plant. Our study thus provides first insights into its genomic organization, evolutionary history, and WGD event and thus becomes an important resource for future genetic and biotechnological studies to understand essential pathways and assist breeding programs for trait enhancements.

genomics↗

bioRxiv2025

Nucleotide and metalloid-driven conformational changes in the arsenite efflux ATPase ArsA

A common mechanism of arsenic detoxification in bacteria is arsenite (AsIII) efflux facilitated by the ArsAB pump that couples metalloid transport to ATP hydrolysis. The cytoplasmic ATPase component, ArsA, binds and hydrolyzes ATP and facilitates the transfer of AsIII to the integral membrane transporter, ArsB. The underlying molecular mechanism of AsIII efflux by ArsAB remains unclear. ArsA is a member of the Intradimeric Walker A (IWA) family of ATPases that undergo dramatic nucleotide-dependent conformational changes to facilitate their respective biological functions. Similar conformational transitions in ArsA have been postulated to drive AsIII binding and transport via ArsB but have not been demonstrated. Here, we report multiple structures of ArsA determined by single-particle cryogenic electron microscopy in an open MgADP-bound state, open MgATP-bound state, and a distinct closed MgATP-bound state liganded to AsIII. Using X-ray absorption spectroscopy, we confirmed that AsIII coordinates three conserved cysteines at the metalloid-binding site of the closed state in a three-coordinate fashion. Coupled with biochemical characterization, our cryo-EM structures reveal key conformational changes in the ArsA catalytic cycle consistent with other members of the IWA family and provide the structural basis for allosteric activation of nucleotide hydrolysis by AsIII. This work enhances our understanding of how the ArsA catalytic cycle regulates metalloid efflux by ArsB.

biochemistry↗

bioRxiv2025

Micro-invasive probes for monitoring electrical and chemical neural activity in nonhuman primates

We leveraged carbon fiber materials for creating sensors that provide dual neurochemical and electrical neural activity recording at micro-invasive (10 {micro}m) spatial footprints proximal to recording sites, and enabling these measurements from deep brain targets of primates with conventional cranial chambers. These shaft-assisted micro-invasive probes (s-{micro}IPs) are approximately 10 {micro}m in diameter along the distal length (1 - 15 mm) immediately surrounding the targeted recording site. This micro-invasive portion ensures that the recording site is isolated from tissue damage induced by the wider shaft portion of the device. The shaft (150 - 165 {micro}m in diameter) within the device stiffens the remaining length of the probe (> 100 mm), and provides compatibility with standard intracranial insertion protocols (e.g., guide tubes and chamber setups) that require a sufficiently rigid and long shaft for deep brain insertion in monkeys. The s-{micro}IP was further expanded to provide dual-channel chemical and electrical neural activity recording with micrometer spatial resolution. Measurements of reward- and movement-related dopamine, spikes, and local field potentials were made from single and dual-channel s-{micro}IPs implanted in task-performing monkeys. Recordings from chronically implanted s-{micro}IPs display the capability of functional multi-modal (chemical and electrical) neural activity measurements over 1-year post-implantation from micro-invasive devices.

bioengineering↗

bioRxiv2024

A High-quality Genome Assembly of Annona squamosa (Custard Apple) Provides Functional Insights into an Emerging Fruit Crop

Annona squamosa, also known as custard apple, is an emerging fruit crop with medicinal significance. We constructed a high-quality genome of A. squamosa along with transcriptome data to gain insights into its phylogeny, evolution and demographic history. The genome has an N50 value of 93.2 Mb assembled into seven pseudochromosomes. The demographic history showed a continuous decline in the effective population size of A. squamosa. Phylogenetic analysis revealed that magnoliids were sister to eudicots, whereas ASTRAL gene trees showed discordance due to incomplete lineage sorting (ILS). Genome syntenic and Ks distribution analyses confirmed the absence of a recent whole genome duplication event in the A. squamosa. Gene families related to photosynthesis, oxidative phosphorylation and plant thermogenesis were found to be highly expanded in the genome. Comparative analysis with other magnoliids revealed the adaptative evolution in the genes of flavonoid biosynthesis pathway, amino sugar, nucleotide sugar and sucrose metabolism, conferring medicinal value and enhanced hexose sugar accumulation. In addition, we performed genome-wide identification of SWEET genes. Our high-quality genome and evolutionary insights of this emerging fruit crop, thus, serve as a valuable resource for advancing studies in functional genomics, evolutionary biology, and crop improvement.

genomics↗

bioRxiv2024

Pseudomonas aeruginosa-mediated cardiac dysfunction is driven by extracellular vesicles released during infection

Pseudomonas aeruginosa (P.a.) is a gram-negative, opportunistic bacterium abundantly present in the environment. Often P.a. infections cause severe pneumonia, if left untreated. Surprisingly, up to 30% of patients admitted to the hospital for community- acquired pneumonia develop adverse cardiovascular complications such as myocardial infarction, arrhythmia, left ventricular dysfunction, and heart failure. However, the underlying mechanism of infection-mediated cardiac dysfunction is not yet known. Recently, we demonstrated that P.a. infection of the lungs led to severe cardiac electrical abnormalities and left ventricular dysfunction with limited P.a. dissemination to the heart tissue. To understand the mechanism of cardiac dysfunction during P.a. infection, we utilized both in vitro and in vivo models. Our results revealed that inflammatory cytokines contribute but are not solely responsible for severe contractile dysfunction in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Instead, exposure of hiPSC-CMs with conditioned media from P.a. infected human monocyte-derived macrophages (hMDMs) was sufficient to cause severe contractile dysfunction and arrhythmia in hiPSC-CMs. Specifically, exosomes released from infected hMDMs and bacterial outer membrane vesicles (OMVs) are the major drivers of cardiomyocyte contractile dysfunction. By using LC-MS/MS, we identified bacterial proteins, including toxins that are packaged in the exosomes and OMVs, which are responsible for contractile dysfunction. Furthermore, we demonstrated that systemic delivery of bacterial OMVs to mice caused severe cardiac dysfunction, mimicking the natural bacterial infection. In summary, we conclude that OMVs released during infection enter circulation and drive cardiac dysfunction.

immunology↗

bioRxiv2024

Mouse olfactory system acts as anemo-detector and -discriminator

Airflow detection while smelling is a fundamental requirement for olfaction, yet the mechanisms underlying such multimodal processing in the olfactory system remain unknown. We report here that mice can learn to accurately discriminate airflow with parallel processing of both mechanical and chemical stimuli revealed by modulated sniffing and refined calcium signaling in the olfactory bulb inhibitory network. Genetic perturbation of AMPAR function and optogenetic control bidirectionally shifted airflow discrimination learning pace, with contrasting phenotypes observed for odor learning, engagement of inhibitory circuits, and setting the optimal inhibition level for stimulus refinement. Multimodal odor-airflow stimuli at subthreshold levels enhanced learning, demonstrating that mechanical stimuli heighten olfactory perception. Our results, thus explain the multimodality of olfaction, and reveal an unexplored dimensionality of odor perception.

neuroscience↗

bioRxiv2024

Autoaggregation in Streptococcus intermedius is driven by the Pel polysaccharide

The Streptococcus Milleri Group (SMG) comprising of Streptococcus intermedius, anginosus and constellatus are commensal bacteria commonly found in healthy individuals. These bacteria are increasingly being recognized as opportunistic pathogens that can cause purulent infections at sterile body sites and have also been identified in the sputum of individuals with cystic fibrosis. Although the mechanisms of conversion to opportunistic pathogens are not well understood, auto-aggregation is a key driver of biofilm adhesion and cohesion in many Streptococci and Staphylococci. Here, we identify a gene cluster in the S. intermedius genome with significant homology to the pel operons in Bacillus cereus and Pseudomonas aeruginosa, which are required for Pel exopolysaccharide production and biofilm formation in these species. Characterization of a panel of clinical S. intermedius strains identified a range of aggregating phenotypes. Analysis of the pel operon in the hyper-aggregating C1365 strain revealed that each of the canonical pelDEADAFG genes, but not the four additional genes are required for aggregation. Further, we demonstrate that C1365 produces a GalNAc-rich exopolysaccharide and that aggregates can be disrupted by the 1,4 N-acetylgalactosaminidases, PelA and Sph3, but not other glycoside hydrolases, proteinase K or DNase I. Using an abscess model of mouse infection, we show that Pel driven aggregation leads to longer lasting infections, and that lack of Pel allows for the bacteria to be cleared more effectively. The polymer also affects how the bacteria interacts with the host immune system. Collectively, our data suggest that the pel operon has relevancy to S. intermedius pathogenicity.

microbiology↗