Biology subjects

Chakraborty, R.

Publications and source records attributed to Chakraborty, R..

At least 19 recordsLinked to original sources

bioRxiv2026

Nitrotoxin metabolism in bacteria may have emerged from a diverse oxidoreductase reservoir

Bacterial transformation of 3 nitropropionic acid (3NPA) is typically viewed through canonical nitronate monooxygenases (NMOs), yet sequence annotation poorly resolves function across this flavoprotein family. Here we show that the environmental YrpB/NMO associated oxidoreductase space is dominated by YrpB related proteins: across 13 metagenomes, 83.1% of 390 conserved domain supported candidates were YrpB-associated. Cultivation along an Eisenia fetida feed gut cast continuum recovered 31 phylogenetically diverse 3NPA responsive bacteria, revealing that this phenotype is distributed across multiple lineages. Using the previously genome-sequenced Serratia sp. EWG9 as a tractable exemplar, we demonstrate sustained 3NPA supported growth, 44% parent compound depletion and a broad early transcriptional reorganization. Its focal oxidoreductase OXR01 occupies overlapping YrpB/NMO sequence space and shows stable predicted 3NPA accommodation without strong transcriptional induction. These findings reposition canonical NMOs as one component of a broader, ecologically distributed oxidoreductase reservoir for bacterial nitrotoxin responsiveness.

microbiology↗

bioRxiv2026

Boron-induced microbial filtering delays early rhizosphere establishment in agricultural soil

Excessive application of boron-based fertilizers in agriculture has led to increased boron accumulation in soil, adversely affecting microbial communities and plant species, ultimately contributing to boron-induced desertification. This study presents the first metagenome-based analysis of boron-contaminated agricultural soil in Northern West Bengal, India, providing a comprehensive profile of the soil microbiome under boron stress. Boron-amended and unamended agricultural soil samples were analyzed using metagenomics sequencing approach over 365 days under natural environmental conditions. The results revealed a significant decline in bacterial diversity in boron-amended soil, with Firmicutes emerging as the dominant phylum. Notably, all boron-tolerant bacterial strains belonged to Firmicutes, suggesting that high boron levels impose selective pressure favouring Gram-positive bacteria. The enrichment of metal-resistant and oligotrophic bacterial taxa in boron-amended soil underscores microbial adaptation to boron stress. In addition to microbial community dynamics, we investigated plant succession in boron-enriched soil, offering novel insights into the interplay between above- and below-ground ecosystems. Our findings highlight two key adaptive traits, high boron tolerance and oligotrophic survival strategies, that enable bacterial communities to persist in boron-rich environments. These results enhance our understanding of microbial resilience in chemically stressed soils and have implications for soil health and sustainable agriculture.

microbiology↗

bioRxiv2026

Convergent genomic variation and wild-type composite RNA-seq profiling identify candidate modules associated with 3-nitropropionic acid utilization in Leclercia barmai

3-Nitropropionic acid (3-NPA) is a toxic nitroaliphatic compound, but the genomic basis of bacterial adaptation to 3-NPA remains incompletely resolved, especially in organisms lacking a canonical nitronate monooxygenase. Here, we used phenotype screening, whole-genome resequencing, targeted UHPLC-MS/MRM, and composite RNA-seq profiling to investigate 3-NPA utilization in Leclercia barmai EMC7. Following attempted Tn5-Mob mutagenesis and kanamycin-based recovery, two independently derived mutants, LTM01 and LTM14, showed impaired growth under 3-NPA-dependent minimal conditions. No stable transposon insertion was detected in either mutant. Comparative genome analysis instead revealed convergent loss-of-function (LOF) mutations affecting amino acid metabolism, nitrogen allocation, central carbon metabolism, cofactor-linked functions, transport, and metal-redox homeostasis, while the predicted flavin-dependent nitro-redox candidate and canonical nitrate/nitrite reduction loci were not disrupted. Targeted UHPLC-MS/MRM analysis showed that wild-type EMC7 depleted approximately 50% of 3-NPA within 36 h, whereas the mutants displayed poor 3- NPA-utilization phenotypes under the same growth framework. Wild-type RNA-seq under glucose-3NPA relative to glucose-KNO3 identified a broad expression profile involving flavin-redox functions, nitrogen assimilation, oxidative-stress response, envelope stress, efflux, cofactor metabolism, and iron homeostasis. Integration of mutant LOF profiles with wild-type gene expression data showed that several disrupted genes or functional counterparts belonged to modules showing expression changes during the wild-type glucose-3NPA response. These findings identify candidate adaptive modules associated with 3-NPA utilization in EMC7, including nitrogen redistribution, carbon entry, sulfur-redox support, cofactor supply, transport, envelope remodeling, and metal-redox control. These results extend the landscape of metabolic adaptation beyond canonical pathways in environmental bacteria.

microbiology↗

bioRxiv2026

A Two-Arm Metabolic-Efflux Adaptation Framework in Klebsiella pneumoniae under Mixed Pharmaceutical Exposure: rutA-Linked Oxidative Entry and rutR-Associated Regulation

Chemically complex pharmaceutical mixtures in wastewater and sludge can affect microbial adaptation; however, the responses to different co-occurring compounds have not been elucidated well. In this study, the adaptation of a strain derived from hospital sludge, Klebsiella pneumoniae SS02, to 17-ethinylestradiol (EE2), warfarin sodium, and their combination has been studied. The organism grows under all three conditions, and pre-exposure experiments show induction and cross-induction to substrates. UHPLC MS/MS analyses demonstrated that there is conditional depletion of the parent compound EE2 by [~]15% at 36 h post-treatment compared to initial concentrations, but not for the abiotic and non-adapted controls. The rate of warfarin sodium depletion was approximately [~]30% within 36 h and was in accordance with first order kinetics (k = 0.0102 /h; t{square}/{square}= 67.9 h). Under the combined treatment regime, there was a delay in warfarin sodium depletion, suggesting staged substrate consumption. Growth inhibition with efflux inhibitors confirmed transport-driven tolerance. A genome-based study revealed the coordinated response strategy that involved a proposed flavin-dependent monooxygenase (RutA), an oxidative entry into the pathway; redox processing linked to Hpa; aromatic metabolism through {beta}-ketoadipate pathway; and RND efflux system. The structural study additionally supported ligand-mediated decrease in DNA binding affinity of RutR, which is in agreement with de-repression of the substrate-activated regulatory mechanism. All these findings lead to the development of a dual-strategy for adaptation model in which oxidative modification and efflux-mediated protection work together under the influence of a mixture of pharmaceuticals.

microbiology↗

bioRxiv2026

Enrichments along gradients resolve eco-evolutionary forces on subsurface microbiomes

How a single gram of soil harbors billions of microorganisms, each with distinct genomic variants that collectively maintain coherent ecological function(s), is one of microbiologys grand unsolved problems. A key obstacle is determining which variants contribute to individual- and community-level fitness, in which contexts, and how co-occurring ecotypes interact to divide niche space. Here, using nitrate (NO3-)-contaminated subsurface sediment as inoculum, we have performed high throughput enrichments in laboratory media of defined carbon source compositions across ecologically relevant gradients of pH and NO3-. Long-read metagenomics and link-community decomposition of co-occurrence networks of taxa across these enrichments has revealed context-specific functional interactions among dominant generalist and lower-abundance specialist denitrifier ecotypes that comprise 53 distinct enriched communities (EnComs) across 288 enrichments derived from a single sediment sample. We identified a single enzymatic difference of alternative NO3- reductases (NapAB vs. NarGHI) with differing substrate affinities that provided a mechanistic explanation for competitive niche partitioning between the two dominant taxa, Neorhizobium spp. and Allorhizobium spp., along the NO3- gradient. Genome-wide polymorphism ratios (pN/pS) revealed that selective pressures vary systematically with carbon source availability and gradients of pH and NO3-, which helps explain the natural biodiversity and functional interactions of ecotypes within denitrifying communities in the subsurface sediment. Our findings show that controlled enrichments along ecological gradients can thus uncover eco-evolutionary forces of selection, drift, and diversification that sculpt the biodiversity of microbial populations in the natural environment.

microbiology↗

bioRxiv2026

Sustained presence of metabolically active mesophiles in the boiling vent-water of a low-salinity, slightly-alkaline, sulfate-rich geothermal spring characterized by an inequitable ecology of hyperthermophiles and thermophiles

Geothermal vent-heads exclusively support the proliferation of (hyper)thermophilic microorganisms. However, diverse mesophiles are stochastically thrust into these ecosystems by local geodynamic forces, and their population-level responses to the unfamiliar stressor hold critical implications for lifes intrinsic resilience to biophysical adversities. Here, we report a time-course exploration of the boiling vent-water of a Trans-Himalayan geothermal spring to determine the population dynamics, in situ functionalities, and potential ecological roles of mesophilic incomers in the context of indigenous (hyper)thermophiles. The temporally-consistent (hyper)thermophilic core-community, predominated in turn by a few Aquificia and Thermoproteota, was delineated as metagenome-assembled genomes. Mesophiles/moderate-thermophiles were identified as MAGs and/or pure-cultures, and whether temporally-consistent/inconsistent, had far lower prevalence. Overall, in situ transcriptional activity and prevalence had significant positive correlation; but many species exhibited high activity despite low prevalence and vice versa, implicating the decoupling of global metabolism from growth/proliferation. Bulked metatranscriptomic signatures identified the (hyper)thermophiles as primary producers of the ecosystem. Populations of mesophiles and moderate-thermophiles were apparently active, but not growing, in situ, with some being engaged in environment detoxification, and production of nutrients, metabolites and protective-biomolecules wanting in the (hyper)thermophiles. The findings engender an unprecedented portrayal of geothermal-vents as multi-community ecosystems where unfamiliar immigrants provide critical metabolic services.

microbiology↗

bioRxiv2026

Ultra-long stable biomimetic nanoparticle Click-ed-to-cancer membrane for anti-cancer treatment

Cancer cell membrane coated biomimetic nanoparticles have been shown to be highly efficient in cellular uptake, homotypic tumour targeting, and the ability to suppress tumour growth compared to uncoated nanoparticles. Long duration anti-cancer treatment regimens require highly stable cancer cell membrane coated biomimetic nanoparticle. To manufacture such highly stable cancer cell membrane coated biomimetic nanoparticle, we used "Click-chemistry" to encapsulate cancer cell membrane on nanoparticles. In situ characterization was done to confirm the functionality of the novel Click-chemistry based formulation to encapsulate cancer cell membrane on nanoparticles. Gold nanoparticles were encapsulated with the cell membranes of cell lines of lung adenocarcinoma, malignant melanoma, high-grade serous epithelial ovarian cancer, colorectal cancer, oral cancer, esophageal adenocarcinoma, adenoid cystic carcinoma of salivary gland, and breast cancer. Functional group analysis, size, morphology, and surface charge confirmed long-stability of the biomimetic nanoparticles after incubating in complete growth medium for 12-months.

bioengineering↗

bioRxiv2026

Functionalized nanoparticle transforms cold to hot adenoid cystic carcinoma of salivary gland tumour microenvironment in vitro

Adenoid cystic carcinoma (ACC) of salivary gland is a "immune-cold" tumour. Annexin A3 (ANXA3) is an apoptotic protein found to be participating in immune cell infiltration in tumour microenvironment (TME) of various cancer cases. Significant low expressions of ANXA3 protein found in adenoid cystic carcinoma. We hypothesized overexpressing ANXA3 transforms ACC "cold" TME to "hot". We cultured UM-HACC-2A and UFH2 spheroids on extracellular matrix and co cultured them with peripheral blood mononuclear cells. We functionalized FDA (The Food and Drug Administration) approved Poly(lactic-co-glycolic acid) PLGA nanoparticles with anti-cMyb antibody and ANXA3 recombinant protein using streptavidin-biotin conjugation. Upon overexpressing ANXA3 in ACC spheroids in immune coculture model using functionalized nanoparticles, significant increase of tumour infiltrating lymphocytes and decrease in the size of the ACC spheroids observed. Apoptotic profiler assay further confirmed significant upregulation of apoptotic proteins, some of them participate in immune infiltration. Overall, this project exhibits promising results showing potential approach to convert ACC into an immune "hot" tumour.

cancer biology↗

bioRxiv2026

Memory erasure by dopamine-gated retrospective learning

Erasing outdated memories is crucial for adaptive behavior. Yet once a cue-outcome association is learned, repeated cue exposure without outcome suppresses conditioned behavior without erasing the underlying memory. This allows rapid behavioral recovery when outcomes are reintroduced. Here, we confirm this limitation for standard "prospective extinction" protocols that present cues without the associated outcome, but show that true memory erasure is achieved by inverting the paradigm: presenting outcomes without associated cues, i.e., "retrospective extinction". We demonstrate that orbitofrontal cortex activity at outcome is necessary for the rapid behavioral recovery following prospective extinction, and that mesolimbic dopamine activity at outcome is necessary for retrospective extinction. These findings reconceptualize extinction mechanisms and suggest complementary strategies to mitigate relapse and erase maladaptive memories.

neuroscience↗

bioRxiv2025

Small RNA-Mediated Metabolic Reprogramming Enables Ciprofloxacin Utilization in Klebsiella sp. SG01

Small regulatory RNAs (sRNAs) play a key role in the complex regulatory networks that bacteria use to adapt to antibiotic stress. This study clarifies how sRNAs help Klebsiella sp. SG01 metabolically adapts to ciprofloxacin (CIP). Nine potential sRNAs that target important metabolic and stress-response pathways were identified by transcriptomic profiling, including glmZ, sgrS, gcvB, and spot42, as well as an FMN riboswitch. TargetRNA3 and IntaRNA functional annotation predicted regulatory effects on TCA cycle flux, redox balance, and the transport of sugars and amino acids. Interestingly, repression of CRP and upregulation of spot42 imply that byproducts of CIP degradation resemble a glucose-rich state. This conjecture was supported by metabolomics, which verified the buildup of short-chain acids and purine intermediates. A change in regulation was also noted, with ProQ and CsrA levels rising in tandem with Hfqs downregulation. Our knowledge of microbial metabolic plasticity under xenobiotic pressure has been expanded by these findings, which collectively reveal a novel post-transcriptional mechanism that permits antibiotic assimilation and stress resilience in bacteria.

microbiology↗

bioRxiv2025

α-Synuclein aggregates induce mitochondrial damage and trigger innate immunity to drive neuron-microglia communication

Tunneling nanotubes (TNTs) enable direct intercellular transfer of macromolecules, organelles, and pathogenic protein aggregates. While -synuclein (-Syn) aggregates are known to promote TNT formation, the underlying mechanisms remain poorly defined. Here, using human neuronal and microglial cell lines, as well as iPSC-derived dopaminergic neurons and microglia, we show that -Syn aggregates induce severe mitochondrial damage, leading to cytosolic release of mitochondrial DNA (mtDNA) and activation of the cGAS-STING-NF- {kappa}B-IRF3 pathway. This innate immune response drives actin cytoskeleton remodeling and the formation of TNT-like structures, promoting intercellular transfer of -Syn from neurons to microglia. Additionally, neuronal cells transfer damaged mitochondria to microglia, where they undergo lysosome-mediated degradation. Neuron-to-microglia communication under -Syn- induced stress also triggers a bystander inflammatory response in microglia, suggesting a neuroimmune activation. Our findings identify mitochondrial damage and STING-mediated inflammation as key drivers of TNT formation and -Syn propagation, highlighting new potential targets to modulate disease progression in Synucleinopathies.

cell biology↗

bioRxiv2025

Spatial Analysis of Placentae During Congenital Cytomegalovirus Infection Reveals Distinct Cellular Profiles in Immune Cells and Trophoblasts

Withdrawal StatementThe authors have withdrawn the manuscript because the data it contained has been updated. Consequently, they request that this work should not be cited as a reference for any projects to ensure the use of the most current information. For any questions or further clarifications, readers are encouraged to contact the corresponding author directly

immunology↗

bioRxiv2025

Artesunate Alleviate Kidney Fibrosis by Restoring Klotho Protein and Suppressing Wnt/β-Catenin Signalling Pathway

Chronic kidney disease (CKD) is a global health concern that often progresses to renal failure and premature death. Regardless of etiology of CKD, kidney fibrosis is the main determinant of progressive CKD. Renal fibrosis is characterized by excessive collagen and extracellular-matrix (ECM) deposition, which impairs renal function with an irreversible loss of nephrons. Currently, there are no effective antifibrotic therapies to halt the progression of CKD to the end-stage kidney failure (ESKF). Artesunate has recently shown antifibrotic effects in various animal models, but its efficacy in renal fibrosis remains unexplored. In this study, the efficacy of artesunate was evaluated in a unilateral ureteral obstruction (UUO) mouse model and in primary human kidney fibroblasts (HKF). Mechanistic investigation including immunoblot analysis, immunohistochemistry, gene expression assay, enzyme-linked immunosorbent assay (ELISA) and other tools were used to study the underlying molecular mechanisms of antifibrotic effects of artesunate. Results of this study showed that artesunate ameliorated multiple profibrotic pathways including transforming growth factor-beta (TGF-{beta}) expression in UUO model and reduced profibrotic markers including alpha-smooth muscle actin (-SMA), fibronectin, collagen I, and vimentin in both in-vivo and in-vitro models. Mechanistic studies indicated that artesunate treatment abrogated the TGF-{beta}/SMAD pathway, restored klotho-protein expression and attenuated both PI3K/Akt and Wnt/{beta}-catenin pathways. Additionally, artesunate inhibited cell proliferation in UUO and induced ferroptosis in HKF cell culture. In conclusions our study demonstrates that artesunate treatment abrogated fibroblast activation, attenuated canonical and non-canonical TGF-{beta} pathways, inhibited cell proliferation in UUO and selectively induced ferroptosis in HKF cell culture, which may offer a potential treatment to attenuate kidney fibrosis and progressive CKD. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=121 SRC="FIGDIR/small/644310v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@1d70fe3org.highwire.dtl.DTLVardef@5423e7org.highwire.dtl.DTLVardef@12866org.highwire.dtl.DTLVardef@37f1d_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2025

Impaired Macrophage DNase Secretion Promotes Neutrophil Extracellular Trap Mediated Defective Efferocytosis in Atherosclerosis

Neutrophil extracellular traps (NETs) drive atherosclerosis progression and are associated with adverse clinical outcomes like myocardial infarction and stroke. While the triggers of NETosis in atherosclerotic plaque are well-characterized, the mechanisms underlying NET degradation and clearance remain unclear. Moreover, the impact of impaired NET clearance on atherosclerosis progression have not been elucidated. Here we show that macrophages are critical for the release of DNases, which degrade NETs. We identified endoplasmic reticulum (ER) stress mediated activation of PERK-ATF4 pathway as a key driver of impaired macrophage DNase secretion, leading to delayed NET clearance and their persistence. Elevated NET levels trigger cleavage of the efferocytosis receptor Mertk leading to defective macrophage efferocytosis and exacerbation of plaque necrosis. Human atherosclerotic plaques and Ldlr-/- mice treated with ISRIB, a PERK inhibitor, show enhanced DNase secretion and clearance of NETs. Together, the identification of key mechanisms of NET clearance in atherosclerosis offers new therapeutic strategies to stabilize plaques.

pathology↗

bioRxiv2025

CPSF6 Promotes HIV-1 Preintegration Complex Function

Cleavage and polyadenylation specificity factor 6 (CPSF6) is part of the cellular cleavage factor I mammalian (CFIm) complex that regulates mRNA processing and polyadenylation. CPSF6 also functions as a HIV-1 capsid (CA) binding host factor and promotes viral DNA integration targeting into gene dense regions of the host genome. However, the effects of CPSF6 on the activity of the HIV-1 preintegration complex (PIC) - the machinery that carries out viral DNA integration to establish infection - is unknown. To study CPSF6s role in HIV-1 PIC function, we extracted PICs from cells depleted of CPSF6 or expressing a CPSF6 mutant that cannot bind to CA. These PICs exhibited significantly lower integration activity when compared to the control PICs. Addition of recombinant CPSF6 restored the integration activity of PICs extracted from the mutant cells, suggesting a direct role of CPSF6 in PIC function. To solidify CPSF6s effect on PIC function, we inoculated CPSF6-depleted and CPSF6-mutant cells with HIV-1 particles and measured viral DNA integration into the host genome. A significant reduction in viral integration in these cells was detected and this defect was not a consequence of reduced reverse transcription or nuclear entry. Additionally, mutant viruses deficient in CA-CPSF6 binding showed no integration defect in CPSF6 mutant cells. Finally, sequencing analysis revealed that HIV-1 integration in the CPSF6 mutant cells was significantly redirected from the gene dense regions of the host genome. Collectively, these results suggest that CPSF6-CA interaction regulates PIC function both in vitro and in infected cells. IMPORTANCEHIV-1 infection is dependent on the interaction of the virus with host factors. However, the molecular details of virus-host factor interactions are not fully understood. For instance, HIV-1 capsid provides binding interfaces for several host factors. CPSF6 is one such capsid-binding host factor, whose cellular function is to regulate mRNA processing and polyadenylation. Initial work identified a truncated cytosolic form of CPSF6 that restricted HIV infection by blocking viral nuclear entry. However, it is now established that the full-length CPSF6 primarily promotes integration targeting into gene dense regions of the host genome. Here we report that CPSF6-CA interaction promotes the activity of HIV-1 preintegration complexes (PICs). We also observed that disruption of CPSF6-CA binding in target cells significantly reduced viral integration and directed integration targeting away from gene-dense regions. These findings demonstrate a critical role for the CPSF6-CA interaction in PIC function and integration targeting.

biochemistry↗

bioRxiv2024

Enzyme-Regulated Non-Thermal Fluctuations Enhance Ligand Diffusion and Receptor-Mediated Endocytosis

Active enzymes during catalyzing chemical reactions, have been found to generate significant mechanical fluctuations, which can influence the dynamics of their surroundings. These phenomena open new avenues for controlling mass transport in complex and dynamically inhomogeneous environments through localized chemical reactions. To explore this potential, we studied the uptake of transferrin molecules in retinal pigment epithelium (RPE) cells via clathrin-mediated endocytosis. In the presence of enzyme catalysis in the extracellular matrix, we observed a significant enhancement in the transport of fluorophore-tagged transferrin inside the cells. Fluorescence correlation spectroscopy measurements showed substantial increase in transferrin diffusion in the presence of active fluctuations. This study sheds light on the possibility that enzyme-substrate reactions within the extracellular matrix may induce long-range mechanical influences, facilitating targeted material delivery within intracellular milieu more efficiently than passive diffusion. These insights are expected to contribute to the development of better therapeutic strategies by overcoming limitations imposed by slow molecular diffusion under complex environments.

biophysics↗

bioRxiv2024

Polycomb Repressive Complex 2 promotes atherosclerotic plaque vulnerability

Key findings1. PRC2 regulates EC shear stress responses. 2. PRC2 governs Klf2/4 suppression downstream of Pcdhg. 3. High PRC2 in ASCVD-prone arterial regions suppresses Klf2/4 to promote ASCVD. 4. Athero-protective Klf2/4 induction upon PRC2 inhibition requires Notch signaling. 5. Tazemetostat, an FDA approved PRC2 inhibitor, slows ASCVD progression and improves markers of plaque stability. Atherosclerotic cardiovascular disease (ASCVD), the leading cause of mortality worldwide, is driven by endothelial cell inflammatory activation and counter-balanced by anti-inflammatory transcription factors Klf2 and Klf4 (Klf2/4). Understanding vascular endothelial inflammation to develop effective treatments is thus essential. Here, we identify, Polycomb Repressive Complex (PRC) 2, which blocks gene transcription by trimethylating histone3 Lysine27 in gene promoter/enhancers, as a potent, therapeutically targetable determinant of vascular inflammation and ASCVD progression. Bioinformatics identified PRC2 as a direct suppressor of Klf2/4 transcription. Klf2/4 transcription requires Notch signaling, which reverses PRC2 modification of Klf2/4 promoter/enhancers. PRC2 activity is elevated in human ASCVD endothelium. Treating mice with established ASCVD with tazemetostat, an FDA approved pharmacological inhibitor of PRC2, slowed plaque progression by 50% and drastically improved markers of plaque stability. This study elucidates a fundamental mechanism of vascular inflammation, thus identifying a potential method for treating ASCVD and possibly other vascular inflammatory diseases.

cell biology↗

bioRxiv2024

Consumption of Ciprofloxacin as the sole Carbon and energy source and Phenomenal Transformation to a Culturable nanometer-sized- bacterium demonstrated by a hospital-waste-water isolate Klebsiella&nbsp sp. SG01

Antimicrobial resistance is a global crisis. Biodegradation by bacteria is an effective strategy to remove the micropollutant from the environment. In this study, we demonstrate that a persistent fluoroquinolone, ciprofloxacin (CIP) can be degraded by a multidrug-resistant Klebsiella sp. SG01 and used as its only carbon source. The degradation was quantified using UV-vis spectroscopy and the degraded product was less toxic than the parent compound as tested against a susceptible Escherichia coli K12. SG01 changes into nano-sized cells as culturable nanobacterium, passes through a 0.22 m pore-size filter while growing on ciprofloxacin, and shows a shorter generation time than cells grown on glucose or rich medium. The basis for the changed growth phenotype of nano-SG01 cells and metabolic changes was partially established by the whole-genome transcriptome. ImportanceFluoroquinolones (FQs) constitute a class of persistent antimicrobials, having a high affinity for sludge, sediments, and soil with reported half-lives of 10.6 days in surface waters and up to 580 days in soil matrices. However, more than 50% consumption or degradation of CIP at higher concentration ([~]2g/L) within 48 hours is not yet reported. Also, the isolate transforms into a nano-form to consume the antibiotic and economizes its metabolism to degrade CIP. From the One Health Approach perspective, nanobacterial transformation is an alarming concern as such viable nanobacteria continue to proliferate and may trigger infection in host. The strategy should be to utilize this powerful strain for the biodegradation of CIP.

microbiology↗