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The species are Gram-negative, facultative intracellular pathogens that invade the colonic epithelium and cause significant diarrheal disease. Despite extensive research on the pathogen, a comprehensive understanding of how initiates contact with epithelial cells remains unknown. maintains many of the same adherence gene operons; however, at least one critical gene component in each operon is currently annotated as a pseudogene in reference genomes. These annotations, coupled with a lack of structures upon microscopic analysis following growth in laboratory media, have led the field to hypothesize that is unable to produce fimbriae or other traditional adherence factors. Nevertheless, our previous analyses have demonstrated that a combination of bile salts and glucose induces both biofilm formation and adherence to colonic epithelial cells. The goal of this study was to perform transcriptomic and genetic analyses to demonstrate that adherence gene operons in strain 2457T are functional, despite the gene annotations. Our results demonstrate that at least three structural genes facilitate 2457T adherence for epithelial cell contact and biofilm formation. Furthermore, our results demonstrate that host factors, namely, glucose and bile salts at their physiological concentrations in the small intestine, offer key environmental stimuli required for adherence factor expression in This research may have a significant impact on vaccine development and further highlights the importance of utilizing -like conditions to study bacterial pathogenesis. Bacterial pathogens have evolved to regulate virulence gene expression at critical points in the colonization and infection processes to successfully cause disease. The species infect the epithelial cells lining the colon to result in millions of cases of diarrhea and a significant global health burden. As antibiotic resistance rates increase, understanding the mechanisms of infection is vital to ensure successful vaccine development. Despite significant gains in our understanding of infection, it remains unknown how the bacteria initiate contact with the colonic epithelium. Most pathogens harbor multiple adherence factors to facilitate this process, but was thought to have lost the ability to produce these factors. Interestingly, we have identified conditions that mimic some features of gastrointestinal transit and that enable to express adherence structural genes. This work highlights aspects of genetic regulation for adherence factors and may have a significant impact on future vaccine development.
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http://dx.doi.org/10.1128/mSphere.00751-19 | DOI Listing |
PLoS One
September 2025
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh.
Objectives: Antibiotic resistance towards penicillin has been attempted to counter by chemically modifying ampicillin through the conjugation with silver nanoparticles (AgNPs). The current study optimizes the conditions for synthesizing and characterizing AgNP-ampicillin to quantify the conjugation extent, evaluate the antibacterial efficacy, and explore the underlying antibacterial mechanisms.
Materials And Methods: AgNPs were synthesized from silver nitrate by chemical reduction method, silica-coated with tetraethyl orthosilicate (TEOS) and amine functionalized by (3-aminopropyl) triethoxysilane (APTES), which was then conjugated with ampicillin via the carbodiimide chemistry.
J Am Soc Nephrol
September 2025
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.
Background: Genetic modifiers are believed to play an important role in the onset and severity of polycystic kidney disease (PKD), but identifying these modifiers has been challenging due to the lack of effective methodologies.
Methods: We generated zebrafish mutants of IFT140, a skeletal ciliopathy gene and newly identified autosomal dominant PKD (ADPKD) gene, to examine skeletal development and kidney cyst formation in larval and juvenile mutants. Additionally, we utilized ift140 crispants, generated through efficient microhomology-mediated end joining (MMEJ)-based genome editing, to compare phenotypes with mutants and conduct a pilot genetic modifier screen.
J Clin Invest
September 2025
Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America.
3-O-sulfation of heparan sulfate (HS) is the key determinant for binding and activation of Antithrombin III (AT). This interaction is the basis of heparin treatment to prevent thrombotic events and excess coagulation. Antithrombin-binding HS (HSAT) is expressed in human tissues, but is thought to be expressed in the subendothelial space, mast cells, and follicular fluid.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2025
Department of Medicine, Institute for Transformative Molecular Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106.
The β-adrenergic receptor (βAR), a prototype G protein-coupled receptor, controls cardiopulmonary function underpinning O delivery. Abundance of the βAR is canonically regulated by G protein-coupled receptor kinases and β-arrestins, but neither controls constitutive receptor levels, which are dependent on ambient O. Basal βAR expression is instead regulated by the prolyl hydroxylase/pVHL-E3 ubiquitin ligase system, explaining O responsivity.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2025
Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur 208016, India.
Agonist-induced interaction of G protein-coupled receptors (GPCRs) with β-arrestins (βarrs) is a critical mechanism that regulates the spatiotemporal pattern of receptor localization and signaling. While the underlying mechanism governing GPCR-βarr interaction is primarily conserved and involves receptor activation and phosphorylation, there are several examples of receptor-specific fine-tuning of βarr-mediated functional outcomes. Considering the key contribution of conformational plasticity of βarrs in driving receptor-specific functional responses, it is important to develop novel sensors capable of reporting distinct βarr conformations in cellular context.
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