Satinder Kaur

All Publications

• Pard3 promotes corneal epithelial stratification and homeostasis by regulating apical-basal polarity, cytoskeletal organization and tight junction-mediated barrier function. The ocular surface Vohra, M., Kumar, S., Sohnen, P., Kaur, S., Swamynathan, S., Hirose, T., Kozmik, Z., Swamynathan, S. K. 2025

  Abstract

  To document the expression of apical-basal polarity (ABP) determinants in the mouse corneal epithelium (CE) and elucidate the functions of Pard3 in establishment and maintenance of ABP, stratification, homeostasis, and barrier function in the CE.Pard3Δ/ΔC mice (Pard3LoxP/LoxP; Aldh3A1-Cre/+) with cornea-specific Pard3 ablation were generated by breeding Aldh3A1-Cre/+ with Pard3LoxP/LoxP mice. The control (Aldh3A1-Cre/+ or Pard3LoxP/LoxP alone) and Pard3Δ/ΔC corneal histology, ocular surface properties, barrier function, and actin cytoskeleton were assessed by Haematoxylin and Eosin staining of paraformaldehyde-fixed, paraffin-embedded tissues, scanning electron microscopy, fluorescein staining, and phalloidin staining, respectively. The expression of specific markers of interest was evaluated by qRT-PCR, immunoblots and immunofluorescent staining.Dynamic changes were observed in the expression and localization of ABP determinants as the CE stratified and matured between post-natal day 5 (PN5) and PN52. Adult Pard3Δ/ΔC CE contained fewer cell layers with rounded basal cells, and loosely adherent superficial cells lacking microplicae. Adult Pard3Δ/ΔC CE also displayed impaired barrier function with decreased expression of tight junction, adherens junction, and desmosome components, disrupted actin cytoskeletal organization, increased proliferation, and upregulation of transcription factors that drive epithelial-mesenchymal transition (EMT).Disruption of ABP in Pard3Δ/ΔC CE, altered expression of cell junction complex components and disorganized actin cytoskeleton, increased cell proliferation, and upregulated EMT transcription factors suggest that the ABP-determinant Pard3 promotes CE features while suppressing mesenchymal cell fate. Collectively, these results elucidate that Pard3-mediated ABP is essential for CE stratification, homeostasis and barrier function.

  View details for DOI 10.1016/j.jtos.2025.04.001

  View details for PubMedID 40188986

• The Secreted Ly6/uPAR-Related Protein-1 (SLURP1) Protects the Cornea From Oxidative Stress. Investigative ophthalmology & visual science Kaur, S., Sohnen, P., Kumar, S., Vohra, M., Swamynathan, S., Swamynathan, S. 2025; 66 (3): 30

  Abstract

  Previously, we reported that the secreted Ly6/uPAR-related protein-1 (SLURP1), abundantly expressed by the corneal epithelium (CE) and secreted into the tear fluid, suppresses NF-κB signaling in healthy corneas and is downregulated in response to a variety of stressors, allowing helpful inflammation to progress. Here we investigate whether SLURP1 manifests its broad protective effects by promoting corneal redox homeostasis.Oxidative stress was induced in the wild-type (WT) and Slurp1-null (Slurp1X-/-) mouse corneas using 1350 J/m2 UV-B, and in human corneal limbal epithelial (HCLE) and SLURP1-overexpressing HCLE-SLURP1 cells with 100 J/m2 UV-B, 0.4 µg/mL mitomycin-C, or 0-100 µM H2O2. We evaluated their (i) redox status (GSH:GSSG ratio) using O-phthalaldehyde; (ii) reactive oxygen species (ROS) accumulation using 2',7'-dichlorodihydrofluorescein diacetate; (iii) antioxidants GPX4, CAT, and SOD2 expression by qRTPCR; (iv) lipid peroxidation by staining for 4-hydroxynonenol, malondialdehyde, and BODIPY-C11; and (v) DNA damage and NF-κB activation by immunostaining for γH2AX, 8-OHdG, NF-κB, and IκB.Slurp1 was significantly downregulated in the UV-B-irradiated WT corneas. Oxidatively stressed HCLE-SLURP1 cells displayed relatively less ROS accumulation, lipid peroxidation, DNA damage and NF-κB activation, and a higher GSH/GSSG ratio and antioxidant gene expression than the similarly treated control HCLE cells. UV-B-irradiated Slurp1X-/- corneas displayed relatively more ROS accumulation, DNA damage and less GPX4 expression than the similarly treated WT corneas.Collectively, these results elucidate that SLURP1 serves as an insult-agnostic immunomodulator that upregulates antioxidants and suppresses ROS accumulation to promote redox homeostasis in corneal epithelial cells and protect them from diverse genotoxic stressors.

  View details for DOI 10.1167/iovs.66.3.30

  View details for PubMedID 40094657

  View details for PubMedCentralID PMC11925223

• In vitro activity of cefepime-tazobactam against oxyimino cephalosporin-resistant clinical isolates of E. coli: exploring a potential carbapenem-sparing strategy. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology Kanaujia, R., Kaur, S., Biswal, M., Ray, P., Sharma, N., Angrup, A. 2025; 44 (3): 753-757

  Abstract

  Cefepime-tazobactam (FEP-TAZ) consists of cefepime combined with tazobactam, a penicillanic acid-sulfone recognized as an established beta-lactamase inhibitor. This study aims to investigate the in-vitro effectiveness of FEP-TAZ against cefepime-resistant clinical isolates of Escherichia coli (E. coli). A total of 105 E. coli clinical isolates characterized by cefepime-resistant/susceptible dose-dependent and carbapenem-sensitive profiles were tested for susceptibility by broth microdilution (BMD) method against cefepime and FEP-TAZ (tazobactam at a fixed concentration of 4 mg/L). Minimum inhibitory concentration (MIC) values for cefepime were determined using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method (M100-2022). Simultaneously, we also performed Disk-diffusion (DD) to observe the concordance between BMD and DD. FEP-TAZ exhibited inhibitory efficacy against 83.8% of E. coli isolates, markedly reducing the geometric mean from 20.4 to 1.9. Comparative analysis with DD revealed concordance with MIC for all isolates except four isolates. FEP-TAZ demonstrated potent activity against E.coli. This may be used as a carbapenem-sparing agent for the treatment of serious infections caused by cefepime-resistant Gram-negative bacilli. Furthermore, in settings where BMD implementation poses challenges, the pragmatic application of DD proves to be a viable alternative.

  View details for DOI 10.1007/s10096-024-05033-0

  View details for PubMedID 39752020

  View details for PubMedCentralID 6563747

• SLURP1 mitigates the corneal epithelial oxidative damage by suppressing the production of reactive oxygen species Kaur, S., Sohnen, P., Swamynathan, S., Kumar, S., Swamynathan, S. K. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2024

  View details for Web of Science ID 001312227705315

• Pard3 controls the retinal pigmented epithelial apical -basal polarity, structure, and function Sohnen, P., Shang, P., Kaur, S., Swamynathan, S., Kumar, S., Hirose, T., Sinha, D., Swamynathan, S. K. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2024

  View details for Web of Science ID 001312227703301

• The Secreted Ly6/uPAR-Related Protein 1 (Slurp1) Modulates Corneal Angiogenic Inflammation Via NF-κB Signaling. Investigative ophthalmology & visual science Swamynathan, S., Campbell, G., Sohnen, P., Kaur, S., St Leger, A. J., Swamynathan, S. K. 2024; 65 (1): 37

  Abstract

  Previously we demonstrated that the secreted Ly-6/uPAR related protein 1 (SLURP1), abundantly expressed in the corneal epithelium (CE) and secreted into the tear fluid, serves as an antiangiogenic molecule. Here we describe the Slurp1-null (Slurp1X-/-) mouse corneal response to silver nitrate (AgNO3) cautery.Five days after AgNO3 cautery, we compared the wild-type (WT) and Slurp1X-/- mouse (1) corneal neovascularization (CNV) and immune cell influx by whole-mount immunofluorescent staining for CD31 and CD45, (2) macrophage and neutrophil infiltration by flow cytometry, and (3) gene expression by quantitative RT-PCR. Quantitative RT-PCR, immunofluorescent staining, and immunoblots were employed to evaluate the expression, phosphorylation status, and subcellular localization of NF-κB pathway components.Unlike the WT, the Slurp1X-/- corneas displayed denser CNV in response to AgNO3 cautery, with more infiltrating macrophages and neutrophils and greater upregulation of the transcripts encoding VEGFA, MMP2, IL-1b, and vimentin. At 2, 7, and 10 days after AgNO3 cautery, Slurp1 expression was significantly downregulated in the WT corneas. Compared with the WT, naive Slurp1X-/- CE displayed increased phosphorylation of IKK(a/b), elevated phosphorylation of IκB with decreased amounts of total IκB, and higher phosphorylation of NF-κB, suggesting that NF-κB signaling is constitutively active in naive Slurp1X-/- corneas.Enhanced angiogenic inflammation in AgNO3 cauterized Slurp1X-/- corneas and constitutively active status of NF-κB signaling in the absence of Slurp1 suggest that Slurp1 modulates corneal angiogenic inflammation via NF-κB signaling.

  View details for DOI 10.1167/iovs.65.1.37

  View details for PubMedID 38252525

  View details for PubMedCentralID PMC10810026

• Molecular nature of ocular surface barrier function, diseases that affect it, and its relevance for ocular drug delivery. The ocular surface Kaur, S., Sohnen, P., Swamynathan, S., Du, Y., Espana, E. M., Swamynathan, S. K. 2023; 30: 3-13

  Abstract

  The structural and functional integrity of the ocular surface, a continuous epithelial structure comprised of the cornea, the conjunctiva, and the ductal surface of the lacrimal as well as meibomian glands, is crucial for proper vision. The ocular surface barrier function (OSBF), sum of the different types of protective mechanisms that exist at the ocular surface, is essential to protect the rest of the eye from vision-threatening physical, chemical, and biological insults. OSBF helps maintain the immune privileged nature of the cornea and the aqueous humor by preventing entry of infectious agents, allergens, and noxious chemicals. Disruption of OSBF exposes the dense nerve endings of the cornea to these stimuli, resulting in discomfort and pain. This review summarizes the status of our knowledge related to the molecular nature of OSBF, describes the effect of different ocular surface disorders on OSBF, and examines the relevance of this knowledge for ocular drug delivery.

  View details for DOI 10.1016/j.jtos.2023.08.001

  View details for PubMedID 37543173

  View details for PubMedCentralID PMC10837323

• KLF4 promotes genomic stability and suppresses ferroptosis in corneal epithelial cells exposed to genotoxic conditions Kaur, S., Vohra, M., Mondal, M., Sohnen, P., Swamynathan, S., Tiwari, A., Swamynathan, S. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2023

  View details for Web of Science ID 001053795602229

• Role of apicobasal polarity in retinal pigmented epithelial cells evaluated by ablation of Pard3 Sohnen, P., Shang, P., Kaur, S., Swamynathan, S., Hirose, T., Sinha, D., Swamynathan, S. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2023

  View details for Web of Science ID 001053795600265

• Secreted Ly-6/uPAR Related Protein-1 (SLURP1) Suppresses TGF-b Induced Epithelial to Mesenchymal Transition in Corneal Epithelial Cells Swamynathan, S., Sohnen, P., Kaur, S., Swamynathan, S. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2023

  View details for Web of Science ID 001053795601127

• In-vitro susceptibility testing methods for the combination of ceftazidime-avibactam with aztreonam in metallobeta-lactamase producing organisms: Role of combination drugs in antibiotic resistance era. The Journal of antibiotics Sreenivasan, P., Sharma, B., Kaur, S., Rana, S., Biswal, M., Ray, P., Angrup, A. 2022; 75 (8): 454-462

  Abstract

  Resistance in Gram-negative organisms has become one of the leading threats in recent years. Of the different mechanisms described in the literature, resistance due to beta-lactamases genes have been overcomed by the use of a beta-lactamase inhibitor in combination with a beta-lactam antibiotic. When this combination is insufficient to counter metallo-beta-lactamases, a third antibiotic, has been added to restore susceptibility. One such recent combination is ceftazidime-avibactam with aztreonam. In this study, 60 isolates of multidrug-resistant organisms producing metallo-beta-lactamases were included to perform in-vitro antibiotic susceptibility testing against ceftazidime-avibactam and aztreonam alone and in combination using three different methods. Individual testing revealed 100% (60/60) resistance to both ceftazidime-avibactam and aztreonam in all the isolates. The disk diffusion method showed an inhibition zone size of 21 mm in all the isolates, with 16 isolates showing an increase in inhibition zone size of >16 mm. In the E-test fixed ratio method, MICs of ceftazidime-avibactam and aztreonam when used alone ranged from 8/4 µg l-1 to ≥256/4 µg l-1 and 16 µg l-1 to 256 µg l-1, respectively, but in combination, these MICs were reduced to 0.016/4 µg l-1 to 2/4 µg l-1 with FIC < 0.5 in all the isolates. Similar results were obtained with the E-test agar dilution method with more than a 16-fold reduction in MIC in all the isolates when avibactam concentration was fixed at 4 µg l-1. All three methods showed a 100% correlation with each other. The current study depicted the usefulness of combining ceftazidime-avibactam with aztreonam against organisms producing metallo-beta-lactamases and that disk diffusion methods can be used as a method for performing in-vitro antibiotic susceptibility testing of this combination.

  View details for DOI 10.1038/s41429-022-00537-3

  View details for PubMedID 35715617

  View details for PubMedCentralID PMC9204069

• Potential Synergistic Antibiotic Combinations against Fluoroquinolone-Resistant Pseudomonas aeruginosa. Pharmaceuticals (Basel, Switzerland) Kothari, A., Jain, N., Kishor Kumar, S., Kumar, A., Kaushal, K., Kaur, S., Pandey, A., Gaurav, A., Omar, B. J. 2022; 15 (2)

  Abstract

  The rise in multiple-drug-resistant (MDR) phenotypes in Gram-negative pathogens is a major public health crisis. Pseudomonas aeruginosa is one of the leading causes of nosocomial infections in clinics. Treatment options for P. aeruginosa have become increasingly difficult due tdo its remarkable capacity to resist multiple antibiotics. The presence of intrinsic resistance factors and the ability to quickly adapt to antibiotic monotherapy warrant us to look for alternative strategies like combinatorial antibiotic therapy. Here, we report the frequency of P. aeruginosa multidrug-resistant and extensively drug-resistance (XDR) phenotypes in a super-specialty tertiary care hospital in north India. Approximately 60 percent of all isolated P. aeruginosa strains displayed the MDR phenotype. We found highest antibiotic resistance frequency in the emergency department (EMR), as 20 percent of isolates were resistant to 15 antipseudomonal antibiotics. Presence of plasmids with quinolone-resistance determinants were major drivers for resistance against fluoroquinolone. Additionally, we explored the possible combinatorial therapeutic options with four antipseudomonal antibiotics-colistin, ciprofloxacin, tobramycin, and meropenem. We uncovered an association between different antibiotic interactions. Our data show that the combination of colistin and ciprofloxacin could be an effective combinatorial regimen to treat infections caused by MDR and XDR P. aeruginosa.

  View details for DOI 10.3390/ph15020243

  View details for PubMedID 35215357

  View details for PubMedCentralID PMC8880063

• Genomic insights into evolution of extensive drug resistance in Stenotrophomonas maltophilia complex. Genomics Kumar, S., Bansal, K., Patil, P. P., Kaur, A., Kaur, S., Jaswal, V., Gautam, V., Patil, P. B. 2020; 112 (6): 4171-4178

  Abstract

  We report first complete genomic investigation of extensive drug resistance (XDR) in a nosocomial Stenotrophomonas maltophilia complex strain that is resistant to mainstream drugs (trimethoprim/sulfamethoxazole and levofloxacin). Comprehensive genomic investigation revealed its exclusive fourteen dynamic regions and highly enriched resistome comprising of two sulfonamide resistance genes on two diverse super-integrons of chromosomal origin. In addition, both these integrons harbour array of antibiotic resistance and commonly used disinfectant's resistance genes linked to ISCR elements. Isolation of a novel XDR strain from Indian tertiary care unit belonging to novel ST with diverse array of resistance genes on ISCR linked super-integrons indicates extent and nature of selection pressure in hospitals. Since, repetitive elements have major role in their spread and due to limitations of draft genomes, there is an urgent need to employ complete genome-based investigation for tracking the emergence of XDR at global level and designing strategies of antimicrobial stewardship and disinfection. IMPORTANCE: Hospital settings in India have one of the highest usages of antimicrobials and a heavy patient load. We hereby report a novel clinical isolate of S. maltophilia complex with two super-integrons that harbour array of antimicrobial resistance genes along with biocide and heavy metal resistance genes. Further, the presence of ISCR type of transposable elements on both the integrons indicates their propensity to transfer resistome while their chromosomal origin suggests possibilities for further genomic/phenotypic complexities according to selection pressure. Such complex mobile cassettes in a novel strain is a potential threat to global health care. Hence, to understand the evolution of opportunistic nosocomial pathogen, there is an urgent need to employ cost-effective long read technologies to keep vigilance on novel and XDR pathogens in populous countries. There is also need for surveillance of the usage of disinfectants and other antimicrobials for environmental hygiene and linked/rapid co-evolution of XDR in nosocomial pathogens. Repositories: Complete genome sequence of Stenotrophomonas maltophilia SM866: CP031058.

  View details for DOI 10.1016/j.ygeno.2020.06.049

  View details for PubMedID 32653516

• Pharmacokinetics of colistin in patients with multidrug-resistant Gram-negative infections: A pilot study. The Indian journal of medical research Gautam, V., Shafiq, N., Mouton, J. W., Malhotra, S., Kaur, S., Ray, P. 2018; 147 (4): 407-412

  Abstract

  There is little information concerning intravenously (i.v.) administered colistin in patients with multidrug-resistant (MDR) Gram-negative infections. Thus, this pilot prospective study was undertaken to characterize efficacy and pharmacokinetics of colistin in patients with MDR Gram-negative infections.Nine patients with age >12 yr and MDR Gram-negative infections were included, of whom six were given colistin at the doses of 2 MU, while three patients were given 1 MU i.v. dose every 8 h. Blood samples were collected at different time intervals. Determination of colistin concentration was done by a ultra-high-performance liquid chromatography/mass spectrometry/selected reaction monitoring assay.The area under the plasma concentration-versus-time curve over eight hours (AUC0-8) for colistin after the 1st dose ranged from 3.3 to 16.4 mg×h/l (median, 4.59). After the 5th dose, AUC0-8for colistin ranged from 4.4 to 15.8 mg×h/l (median, 6.0). With minimal inhibitory concentration (MIC) value of 0.125 mg/l, AUC0-8/MIC ranged from 26.7 to 131.4 (median, 36.7) and 35.5 to 126.0 (median, 48.0) after the 1st and the 5th doses of 2 MU every 8 h, respectively.As there is a paucity of information on AUC/MIC for colistin, it may not be possible to conclude whether AUC/MIC values in our patients were adequate. There is a microbiological clearance of organism, which goes in favour of the dosing schedule being adequate. Further studies need to be done to understand the pharmacokinetics of colistin in patients with infections.

  View details for DOI 10.4103/ijmr.IJMR_1464_16

  View details for PubMedID 29998877

  View details for PubMedCentralID PMC6057249