Biology subjects

Choudhary, R.

Publications and source records attributed to Choudhary, R..

6 recordsLinked to original sources

bioRxiv2026

In-vitro evaluation of Ozenoxacin and other Antibiotics against Staphylococcus aureus and Streptococcus pyogenes isolated from Skin and Soft Tissue Infections

Staphylococcus aureus and Streptococcus pyogenes are major causative bacteria responsible for skin and soft-tissue infections (SSTIs) such as impetigo. Increasing resistance to commonly used topical antibiotics necessitates evaluation of newer agents for the treatment of skin infections. Ozenoxacin, a novel non-fluorinated topical quinolone, has shown promise, exhibiting potent activity against a wide range of pathogens, including methicillin-resistant Staphylococcus (MRSA) and Streptococcus pyogenes. The present study compared the in vitro activity of ozenoxacin and comparator agents against clinical isolates of Staphylococcus aureus and Streptococcus pyogenes from multiple sources including skin and soft-tissue, wound, abscess, and blood. Ozenoxacin was assessed for in vitro antimicrobial activity against 109 methicillin-susceptible (MSSA), methicillin-resistant S. aureus (MRSA), and 24 Streptococcus pyogenes isolates by broth microdilution method recommended by the Clinical and Laboratory Standards Institute (CLSI). Ozenoxacin demonstrated potent in-vitro activity against all 109 S. aureus (MIC50/90= 0.125/0.5 {micro}g/ml) and 24 S. pyogenes (MIC50/90= 0.015/0.03 {micro}g/ml) strains. In contrast, higher MICs were observed for fusidic acid and mupirocin among a subset of S. aureus isolates. A comparison of MIC90values demonstrated that ozenoxacin (0.5 {micro}g/ml) was more active against S. aureus isolates than 8 of the 9 comparator agents tested including vancomycin and linezolid (MIC90= 2 & 4 {micro}g/ml) respectively. In vitro studies of ozenoxacin showed potency against staphylococci and streptococci including resistant S. aureus strains. These findings support its role as an effective first-in-class quinolone topical therapeutic option in the management of various SSTIs.

microbiology↗

bioRxiv2025

c-MYC can Form Phase Condensates via its DNA Binding Domain

The c-MYC oncogene is overexpressed in cancers. Phase condensates are membrane-less cellular compartments in cells. Using the optoDroplet system, which leverages optogenetics for condensate dynamics studies, here we showed c-MYC has the capability to form phase condensates. Moreover, the 3 terminus of c-MYC, which contains a DNA binding domain but no intrinsic disordered regions, is sufficient to form phase condensates. Our research contributes to a better understanding of c-MYC biology.

cancer biology↗

bioRxiv2024

RNA Polymerase II Degradation Triggered by DNA Repair Occurs In Trans and Independently of how the Lesion is Recognised

In response to DNA damage, RPB1, the catalytic subunit of RNA Polymerase II (RNAPII), is degraded by the ubiquitin-proteasome system. Degradation models only consider transcriptionally engaged molecules, where a stalled RNAPII complex functions as a lesion recognition factor and its RPB1 subunit is proposed to be subsequently degraded to facilitate access of core Nucleotide Excision Repair (NER) factors. This Transcription Coupled repair is complemented by the Global Genome repair (GG-NER) system, where lesions are recognized by the XPE and XPC factors. Here we show that RPB1 degradation is controlled in trans by a pathway that depends on NER activity, irrespectively of whether the lesion is recognized by RNAPII itself or by GG-NER factors. Incomplete lesion repair due to absence of any core NER factor enhances RPB1 degradation, indicating that the signal controlling RPB1 abundance is started by lesion recognition and continues until DNA repair is completed. Consistent with an in trans mechanism, damage-induced RPB1 degradation is not restricted to active nor phosphorylated RPB1 molecules and depends on Cullin-RING ubiquitin ligases. These findings uncover a repair-dependent mechanism controlling RPB1 levels and provide a rationale for the control of gene expression under stress, where more damage implies more repair and less RPB1 levels, hence restricting RNAPII activity.

molecular biology↗

bioRxiv2022

Increasing evenness and stability in synthetic microbial consortia

Construction of successful synthetic microbial consortia will harbour a new era in the field of agriculture, bioremediation, and human health. Engineering communities is a complex, multi-dimensional problem with several considerations ranging from the choice of consortia members and spatial factors to genetic circuit performances. There has been a growing number of computational strategies to aid in synthetic microbial consortia design, but a framework to optimize communities for two essential properties, evenness and stability, is missing. We investigated how the structure of different social interactions (cooperation, competition, and predation) in quorum-sensing based circuits impacts robustness of synthetic microbial communities and specifically affected evenness and stability. Our proposed work predicts engineering targets and computes their operating ranges to maximize the probability of synthetic microbial consortia to have high evenness and high stability. Our exhaustive pipeline for rapid and thorough analysis of large and complex parametric spaces further allowed us to dissect the relationship between evenness and stability for different social interactions. Our results showed that in cooperation, the speed at which species stabilizes is unrelated to evenness, however the region of stability increases with evenness. The opposite effect was noted for competition, where evenness and stable regions are negatively correlated. In both competition and predation, the system takes significantly longer to stabilize following a perturbation in uneven microbial conditions. We believe our study takes us one step closer to resolving the pivotal debate of evenness-stability relationship in ecology and has contributed to computational design of synthetic microbial communities by optimizing for previously unaddressed properties allowing for more accurate and streamlined ecological engineering.

systems biology↗

bioRxiv2021

Biop-C: A Method for Chromatin Interactome Analysis of Solid Cancer Needle Biopsy Samples

A major challenge in understanding the 3D genome organization of cancer samples is the lack of a method adapted to solid cancer needle biopsy samples. Here we developed Biop-C, a modified in situ Hi-C method, and applied it to characterize three nasopharyngeal cancer patient samples. We identified Topologically-Associated Domains (TADs), chromatin interaction loops, and Frequently Interacting regions (FIREs) at key oncogenes in nasopharyngeal cancer from Biop-C heat maps. Our results demonstrate the utility of our Biop-C method in investigating the 3D genome organization in solid cancers, and the importance of 3D genome organization in regulating oncogenes in nasopharyngeal cancer.

genomics↗

bioRxiv2020

Three-dimensional Genome Organization Maps in Normal Haematopoietic Stem Cells and Acute Myeloid Leukemia

Acute Myeloid Leukemia (AML) is a highly lethal blood cancer arising due to aberrant differentiation of haematopoietic stem cells. Here we obtained 3D genome organization maps by Hi-C in the CD34+ haematopoietic stem cells from three healthy individuals and eight individuals with AML, and found that AML have increased loops to oncogenes compared with normal CD34+ cells. The MEIS1 oncogenic transcription factor is regulated by a Frequently Interacting Region (FIRE). This FIRE is only present in normal bone marrow samples, and four of eight AML sample. FIRE presence is associated with MEIS1 expression. CRISPR excision of a FIRE boundary led to loss of MEIS1 and reduced cell growth. Moreover, MEIS1 can bind to the promoter of HOXA9, and HOXA9 shows gain of Acute Myeloid Leukemia-specific super-enhancers that loop to the HOXA9 promoter. SignificanceWe found that Acute Myeloid Leukemias have more chromatin loops to oncogenes compared with normal blood stem cells. We identified heterogeneity in chromatin interactions at oncogenes, and heterogeneity in super-enhancers that loop to oncogenes, as two key epigenetic mechanisms that underlie MEIS1 and HOXA9 oncogene expression respectively.

cancer biology↗