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Last update 08 May 2025

UMPS

Last update 08 May 2025

Basic Info

Synonyms

ODC, OMPD, OMPdecase

+ [8]

Introduction

Bifunctional enzyme catalyzing the last two steps of de novo pyrimidine biosynthesis, orotate phosphoribosyltransferase (OPRT), which converts orotate to orotidine-5'-monophosphate (OMP), and orotidine-5'-monophosphate decarboxylase (ODC), the terminal enzymatic reaction that decarboxylates OMP to uridine monophosphate (UMP).

Drugs associated with UMPS

KP-27

Target

UMPS

Mechanism

UMPS inhibitors

Active Org.-

Originator Org.

Ontario Institute for Cancer Research

Active Indication-

Inactive Indication

Neoplasms

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with UMPS

100 Translational Medicine associated with UMPS

0 Patents (Medical) associated with UMPS

297

Literatures (Medical) associated with UMPS

25 Feb 2025·Proceedings of the National Academy of Sciences

Enterobacter hormaechei replaces virulence with carbapenem resistance via porin loss

Article

Author: Pironti, Alejandro ; John, Amelia St. ; Torres, Victor J. ; Shopsin, Bo ; DuMont, Ashley L. ; Perault, Andrew I.

Pathogenic Enterobacter species are of increasing clinical concern due to the multidrug-resistant nature of these bacteria, including resistance to carbapenem antibiotics. Our understanding of Enterobacter virulence is limited, hindering the development of new prophylactics and therapeutics targeting infections caused by Enterobacter species. In this study, we assessed the virulence of contemporary clinical Enterobacter hormaechei isolates in a mouse model of intraperitoneal infection and used comparative genomics to identify genes promoting virulence. Through mutagenesis and complementation studies, we found two porin-encoding genes, ompC and ompD , to be required for E. hormaechei virulence. These porins imported clinically relevant carbapenems into the bacteria, and thus loss of OmpC and OmpD desensitized E. hormaechei to the antibiotics. Our genomic analyses suggest porin-related genes are frequently mutated in E. hormaechei , perhaps due to the selective pressure of antibiotic therapy during infection. Despite the importance of OmpC and OmpD during infection of immunocompetent hosts, we found the two porins to be dispensable for virulence in a neutropenic mouse model. Moreover, porin loss provided a fitness advantage during carbapenem treatment in an ex vivo human whole blood model of bacteremia. Our data provide experimental evidence of pathogenic Enterobacter species gaining antibiotic resistance via loss of porins and argue antibiotic therapy during infection of immunocompromised patients is a conducive environment for the selection of porin mutations enhancing the multidrug-resistant profile of these pathogens.

18 Feb 2025·Infection and Immunity

Evaluating small extracellular vesicle-based vaccination across heterologous Salmonella strains isolated from wastewater

Article

Author: Maurelli, Anthony T. ; Ferraro, Mariola J. ; Rainey, Andrew L. ; Bhimani, Saloni ; Emerson, Lisa E.

ABSTRACTSalmonella infections pose significant public health challenges worldwide. The diversity of Salmonella strains, particularly those isolated from environmental and clinical sources, necessitates innovative approaches to prevention and treatment. Previous research has shown that small extracellular vesicles (sEVs) produced by macrophages during Salmonella Typhimurium infection can induce robust immune responses when used as a vaccine, offering complete protection in systemic infection models. In this study, we isolated 120 Salmonella strains from qPCR invA -positive wastewater samples collected in Gainesville, FL. These strains underwent enrichment, selection, and biochemical confirmation, followed by serotyping and whole genome sequencing. Two isolates, Salmonella enterica subsp. diarizonae (Diarizonae) and S. enterica serovar Enteritidis, were selected for further analysis based on community prevalence and clinical severity. We also assessed the ability of sEVs produced by S . Typhimurium-infected macrophages to induce immune responses against these heterologous and circulating strains in mice. Immunization with sEVs induced robust antigen-specific SIgA and IgG responses against S . Typhimurium, Enteritidis, and Diarizonae, with high titers observed in sera and fecal samples. Proteomic analysis revealed differential expression of proteins in these strains, including antigenic proteins present in sEVs such as OmpA, FliC, or OmpD. Moreover, this study highlights the role of wastewater-based epidemiology (WBE) as a tool for environmental surveillance, offering a complementary perspective on Salmonella dynamics within a population. Integrating WBE with traditional surveillance methods, along with the promising results of sEV-based vaccination, provides a pragmatic strategy for developing effective preventative measures against Salmonella infections, addressing the diversity of non-typhoidal Salmonella strains.

02 Dec 2024·Journal of Antimicrobial Chemotherapy

The two-component sensor factor envZ influences antibiotic resistance and virulence in the evolutionary dynamics of multidrug-resistant Salmonella enteritidis causing multisite invasive infections

Article

Author: Wu, Shenghai ; Fu, Ying ; Li, Siying ; Jin, Jie ; Chen, Yan ; Jiang, Yan ; Han, Xinhong ; Yang, Shaoxue ; Yu, Yunsong ; Yu, Lifei ; Zhang, Wang

AbstractObjectivesTo assess the impact of mutations in the two-component sensor envZ on antibiotic resistance and virulence in the evolutionary dynamics of MDR Salmonella enteritidis (S. enteritidis).MethodsFive S. enteritidis isolates obtained from a patient with multisite invasive infections were analysed. Analysis of antibiotic resistance genes, virulence genes and SNP was performed through WGS. RNA sequencing, quantitative RT–PCR, virulence testing in a Galleria mellonella (G. mellonella) infection model and in vitro cell experiments were used to examine the effects of envZ mutations.ResultsWGS revealed identical resistance and virulence genes on an IncFIB(S)/IncFII(S)/IncX1 fusion plasmid in all strains. The faecal strains harboured envZ mutations, reducing outer membrane protein ompD and ompF transcriptional level. Virulence testing demonstrated elevated virulence in envZ mutant strains. In vitro experiments revealed increased adhesion, invasion and phagocytosis resistance in envZ mutants, along with reduced biofilm formation and growth rates.ConclusionsThese findings highlight novel genetic locations on envZ influencing antibiotic resistance and virulence in clinical S. enteritidis strains. envZ mutations impact antibiotic resistance by down-regulating ompD and ompF expression and enhance virulence, contributing to multisite infections with increased fitness costs.

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