Biology subjects

Gajjar, D.

Publications and source records attributed to Gajjar, D..

4 recordsLinked to original sources

bioRxiv2026

Flow-Dependent CFU Dynamics Reshape Polymicrobial Biofilm with a Pronounced Dominance Shift under Sub-Inhibitory Antibiotic Stress

Catheter-associated urinary tract infections (CAUTIs) are the most prevalent healthcare-associated infections globally, yet the ecological dynamics governing polymicrobial biofilm communities on indwelling catheters remain poorly understood under physiologically relevant conditions. Most prior work uses static in vitro models that fail to capture continuous urine flow and sub-inhibitory (sub-MIC) antibiotic gradients. We investigated how continuous flow and sub-MIC concentrations of ciprofloxacin and gentamicin reshape colony-forming unit (CFU) dynamics across attached biofilm and dispersed effluent fractions, and species dominance in mono- and polymicrobial biofilms of Pseudomonas aeruginosa (Pa), Klebsiella pneumoniae (Kp), and Enterococcus faecium (Ef) using silicone-coated latex catheter segments, volumetric infusion pumps, and ibidi {micro}-slide VI 0.4 microfluidic chambers. Under antibiotic-free conditions, Pa dominated both dual co-cultures (Pa+Kp, Pa+Ef) in static condition, but this dominance was not sustained under flow in the Pa+Ef pairing, where Ef rose to 62.5% relative abundance. Sub-MIC ciprofloxacin under flow promoted Kp dispersal (+15.87 log? fold change in dispersed-cell fraction(filter), cooperative Pa recovery via Ef co-occupancy, and pronounced Ef dominance in the triple-species community (64.71% relative abundance). Ef exhibited enhanced growth under sub-MIC gentamicin in static conditions that was abolished under flow. CLSM imaging revealed ciprofloxacin-induced Kp filamentation under flow, with Ef microcolonies localising at filament termini--a novel architectural interaction providing spatial scaffolding for the gram-positive partner. These findings establish that continuous flow and antibiotic class jointly determine polymicrobial dominance outcomes in ways invisible to static assays, underpinning Ef persistence in mature CAUTI biofilms and highlighting flow as a central ecological variable in infection pathogenesis.

microbiology↗

bioRxiv2026

Bioactive Spermidine-Crosslinked DNA Hydrogel for rapid homeostasis and accelerated wound healing

Damage to the skin by trauma, burns, or surgical procedures often results in uncontrolled bleeding, which remains a leading cause of preventable death following injury, yet most conventional hemostatic materials are engineered solely to arrest bleeding and often adhere strongly to the wound bed, causing pain, rebleeding, and disruption of newly formed tissue upon removal. Here, we report a DNA hydrogel that structurally mimics neutrophil extracellular traps (NETs) and is crosslinked using a bioactive small molecule with potent autophagy-inducing, cardioprotective, anti-inflammatory, antioxidant, and mitochondria-protective properties, integrating rapid hemostasis with active support for tissue regeneration in a single biomaterial. The DNA network provides an intrinsically biocompatible, biodegradable scaffold capable of recruiting platelets and erythrocytes to achieve rapid clot formation, while the bioactive crosslinker is released as the network degrades, delivering a sustained cytoprotective and anti-inflammatory stimulus directly at the wound site. The hydrogel was characterised physiochemically and evaluated for cytocompatibility, hemolytic potential, hemostatic efficacy, and wound-healing performance in a murine model. Results demonstrate that the bioactive-crosslinked DNA hydrogel achieves rapid, effective hemostasis, while accelerating wound closure and supporting regenerative tissue remodelling. This dual-function platform offers a promising strategy for next-generation wound-care biomaterials that unite immediate bleeding control with accelerated, natural tissue healing.

bioengineering↗

bioRxiv2025

Programmable DNA-Silk fibroin hydrogel scaffold with temporal mechanical reinforcement for mesenchymal stem cells differentiation and accelerated wound healing in a full-thickness skin defect mice model

DNA-based hydrogels have attracted significant attention in biomedical applications due to their programmability, biocompatibility, and tunable functionalities. However, their clinical translation is hindered by high synthesis costs, limited mechanical strength, poor stability, and complex synthesis protocols. In this work, we present a novel DNA-silk fibroin hybrid hydrogel that overcomes these limitations by combining the unique biofunctionality of DNA with the superior mechanical and chemical properties of silk fibroin. Salmon-derived DNA, an abundant and low-cost source, was incorporated with silk fibroin to form hybrid networks via a simple, scalable process. Silk fibroin served as a robust scaffold, enhancing mechanical strength, controlling degradability, and improving structural stability, while the entangled DNA-silk network reduced rapid DNA degradation. The resulting hybrid hydrogel demonstrated temporal mechanical reinforcement and prolonged stability, with in vitro studies demonstrating that the developed hybrid hydrogel enhanced the chondrogenic and osteogenic differentiation of Infrapatellar Fat Pad Mesenchymal Stem Cells (IFP-MSCs). Additionally, hemostatic and in vivo studies demonstrated the potential of DNA-silk fibroin hydrogel as a promising biomaterial for rapid hemostasis and accelerated wound healing. Overall, the developed DNA-silk fibroin hybrid hydrogel offers strong potential for mesenchymal tissue engineering, hemostatic adjuvant and wound healing.

bioengineering↗

bioRxiv2021

Genomic evolution of the globally disseminated multidrug-resistant Klebsiella pneumoniae clonal group 147

BackgroundThe rapid emergence of multidrug-resistant Klebsiella pneumoniae (Kp) is largely driven by the spread of specific clonal groups (CG). Of these, CG147 includes 7-gene MLST sequence types ST147, ST273 and ST392. CG147 has caused nosocomial outbreaks across the world, but its global population dynamics remain unknown. Here, we report a pandrug-resistant ST147 clinical isolate from India (strain DJ) and define the evolution and global emergence of CG147. MethodsAntimicrobial susceptibility testing (EUCAST guidelines) and genome sequencing (Illumina and Oxford Nanopore technologies, Unicycler assembly) were performed on strain DJ. Additionally, we collated 217 publicly available CG147 genomes (NCBI, May 2019). CG147 evolution was inferred within a temporal phylogenetic framework (BEAST) based on a recombination-free sequence alignment (Roary/Gubbins). Comparative genomic analyses focused on resistance and virulence genes and other genetic elements (BIGSdb, Kleborate, PlasmidFinder, PHASTER, ICEFinder and CRISPRCasFinder). ResultsStrain DJ had a pandrug resistance phenotype. Its genome comprised 7 plasmids and 1 linear phage-plasmid. Four carbapenemase genes were detected: blaNDM-5 and 2 copies of blaOXA-181 in the chromosome, and a second copy of blaNDM-5 on an 84 kb IncFII plasmid. CG147 genomes carried a mean of 13 acquired resistance genes or mutations; 63% carried a carbapenemase gene and 83% harbored blaCTX-M. All CG147 genomes presented GyrA and ParC mutations and a common subtype IV-E CRISPR-Cas system. ST392 and ST273 emerged in 2005 and 1995, respectively. ST147, the most represented phylogenetic branch, was itself divided into two main clades with distinct capsular loci: KL64 (74%, DJ included, emerged in 1994 and disseminated worldwide, with carbapenemases varying among world regions) and KL10 (20%, 2002, predominantly found in Asian countries, associated with carbapenemases NDM and OXA-48-like). Further, subclades within ST147-KL64 differed in the yersiniabactin locus, OmpK35/K36 mutations, plasmid replicons and prophages. The absence of IncF plasmids in some subclades was associated with a possible activity of a CRISPR-Cas system. ConclusionsK. pneumoniae clonal group CG147 comprises pandrug- or extensively-resistant isolates and carries multiple and diverse resistance genes and mobile genetic elements, including chromosomal blaNDM-5. Its emergence is driven by the spread of several phylogenetic clades marked by their own genomic features and specific temporo-spatial dynamics. These findings highlight the need for precision surveillance strategies to limit the spread of particularly concerning CG147 subsets.

genomics↗