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Identification of blaESBL- and blaCARBA- Positive Multi-Drug Resistant Mixta calida Isolates from Distinct Human Hosts.

OBJECTIVE: This study aimed to investigate the identification of blaCARBA-positive multidrug-resistant Mixta calida isolates from human host … ted using a MicroScan panel, following EUCAST and CLSI guidelines. Whole-genome sequencing, plasmid replicon typing, and antibiotic-resistance-gene and virulence-factor profiling were employed. Comparative analysis included all additional canonical M. calida genomes from NCBI database. RESULTS: Both Irish isolates were taxonomically placed as M. calida an …

Recombinant Hepatitis E Viruses Harboring Tags in the ORF1 Protein.

Hepatitis E virus (HEV) is one of the most common causes of acute hepatitis and jaundice in the world. Current understanding of the molecular virology and pathogenesis of hepatitis E is incomplete, due particularly to the limited availability of functional tools. Here, we report the development of tagged HEV genomes as a novel tool to investigate the viral life cycle. A selectable subgenomic HEV replicon was subjected to random 15-nucleotide sequence insertion using transposon-based technology. Viable insertions in the open reading frame 1 (ORF1) protein were selected in a hepatoblastoma cell …

Comparative Genomics and Metabolic Analysis Reveals Peculiar Characteristics of Rhodococcus opacus Strain M213 Particularly for Naphthalene Degradation.

The genome of Rhodococcus opacus strain M213, isolated from a fuel-oil contaminated soil, was sequenced and annotated which revealed a genome size of 9,194,165 bp encoding 8680 putative genes and a G+C content of 66.72%. Among the protein coding genes, 71.77% were annotated as clusters of orthologous groups of proteins (COGs); 55% of the COGs were present as paralog clusters. Pulsed field gel electrophoresis (PFGE) analysis of M213 revealed the presence of three different sized replicons- a circular chromosome and two megaplasmids (pNUO1 and pNUO2) estimated to be of 750Kb 350Kb in size, respe…

Vaccine research efforts for filoviruses.

Ebola and Marburg viruses belong to the family Filoviridae, and cause acute, frequently fatal, haemorrhagic fever in humans and non-human primates. No vaccines are available for human use. This review describes the status of research efforts to develop vaccines for these viruses and to identify the immune mechanisms of protection. The vaccine approaches discussed include DNA-based vaccines, and subunit vaccines vectored by adenovirus, alphavirus replicons, and vaccinia virus.

[DNA replication in intact and X-ray-irradiated cells in the Cockayne syndrome].

Using DNA fiber autoradiography, an estimation was made of DNA replication in normal fibroblasts and in those derived from a patient with Cockayne syndrome. The rate of replication fork movement as well as the rate of DNA chain growth, dependent on the frequency of initiation sites in the adjacent clusters of replicons, did not differ in Cockayne syndrome cells, compared to cells of normal donors, either before or after exposure to ionizing radiation.

Conjugative IncHI1 plasmids drive the emergence of multidrug resistance in Nigerian Salmonella Typhi: A four-decade genomic analysis.

BACKGROUND: The role of plasmids in driving antimicrobial resistance (AMR) in West African Salmonella Typhi remains unexplored. This study investigates the prevalence, temporal dynamics, and genetic associations of plasmid mobility classes and replicon types in Nigerian S. typhi over nearly four decades. RESULTS: We analyzed 151 S. typhi genomes from Nigeria (1982-2018) obtained from EnteroBase. Plasmid replicon typing and mobility classification revealed that 49.7% of isolates harbored conjugative plasmids, with the IncHI1 family (IncHI1A, IncHI1B_R27, and IncFIA_HI1) being the most prevalen…

Global Epidemiological Survey and Genomic Analysis of Multiple Carbapenemases-Producing Citrobacter freundii.

OBJECTIVES: Carbapenem-resistant Citrobacter freundii (CRCF) has emerged as a growing global health concern, as it is increasingly implicate … multi-locus sequence types (MLST), phylogenetic relationships, geographic distribution, and plasmid replicon compositions. RESULTS: Through antimicrobial susceptibility testing, all MCP-CF isolates exhibited extensive resistance to β-lactams, with partial resistance to tigecycline but retained susceptibility to colistin. From the global perspective, MCP-C …

Phylogenomic structure and resistance profiles of clinical Proteus mirabilis from a Thai hospital.

Proteus mirabilis is an opportunistic pathogen associated with urinary tract infections, wound infections, and bacteremia. We analyzed 17 clinical isolates collected from hospitals in Narathiwat Province, southern Thailand, to characterize their antimicrobial resistance (AMR), virulence potential, plasmid replicon content, and genomic relatedness. Most isolates were phenotypically susceptible to all tested antibiotics. Resistance was limited to two strains: KS160 (ceftriaxone, ciprofloxacin, levofloxacin) and KS044 (ciprofloxacin, levofloxacin). Whole-genome analysis, however, identified 50 un…

Multiple polymerase acidic (PA) I38X substitutions in influenza A(H1N1)pdm09 virus permit polymerase activity and cause reduced baloxavir inhibition.

BACKGROUND: Baloxavir marboxil is an antiviral drug that targets the endonuclease activity of the influenza virus polymerase acidic (PA) protein. PA I38T/M/F substitutions reduce its antiviral efficacy. OBJECTIVES: To understand the effects of the 19 possible amino acid (AA) substitutions at PA 38 on influenza A(H1N1)pdm09 polymerase activity and inhibition by baloxavir acid, the active metabolite of baloxavir marboxil. METHODS: Influenza A(H1N1)pdm09 viral polymerase complexes containing all 19 I38X AA substitutions were reconstituted in HEK293T cells in a mini-replicon assay. Polymerase co…

MK-571, a Cysteinyl Leukotriene Receptor 1 Antagonist, Inhibits Hepatitis C Virus Replication.

The quinoline MK-571 is the most commonly used inhibitor of multidrug resistance protein-1 (MRP-1) but was originally developed as a cysteinyl leukotriene receptor 1 (CysLTR1) antagonist. While studying the modulatory effect of MRP-1 on anti-hepatitis C virus (HCV) direct-acting antiviral (DAA) efficiency, we observed an unexpected anti-HCV effect of compound MK-571 alone. This anti-HCV activity was characterized in Huh7.5 cells stably harboring a subgenomic genotype 1b replicon. A dose-dependent decrease of HCV RNA levels was observed upon MK-571 administration, with a 50% effective concentra…

The Rescue and Characterization of Recombinant, Microcephaly-Associated Zika Viruses as Single-Round Infectious Particles.

Zika virus (ZIKV) is transmitted by Aedes mosquitoes and exhibits genetic variation with African and Asian lineages. ZIKV Natal RGN strain, an Asian-lineage virus, has been identified in brain tissues from fetal autopsy cases with microcephaly and is suggested to be a neurotropic variant. However, ZIKV Natal RGN strain has not been isolated; its biological features are not yet illustrated. This study rescued and characterized recombinant, single-round infectious particles (SRIPs) of the ZIKV Natal RGN strain using reverse genetic and synthetic biology techniques. The DNA-launched replicon of Z…

Plasmid evolution in carbapenemase-producing Enterobacteriaceae: a review.

Carbapenem-resistant Enterobacteriaceae (CRE) have been listed by the WHO as high-priority pathogens owing to their high association with mortalities and morbidities. Resistance to multiple β-lactams complicates effective clinical management of CRE infections. Using plasmid typing methods, a wide distribution of plasmid replicon groups has been reported in CREs around the world, including IncF, N, X, A/C, L/M, R, P, H, I, and W. We performed a literature search for English research papers, published between 2013 and 2018, reporting on plasmid-mediated carbapenem resistance. A rise in both carb…

A 7-deaza-adenosine analog is a potent and selective inhibitor of hepatitis C virus replication with excellent pharmacokinetic properties.

Improved treatments for chronic hepatitis C virus (HCV) infection are needed due to the suboptimal response rates and deleterious side effec … n HCV RdRp assays while maintaining the inhibitory potency of the nucleoside in the bicistronic HCV replicon and with reduced cellular toxicity. In contrast, while 7-deaza-2'-C-methyl-GTP also displays enhanced inhibitory potency in enzyme assays, due to poor cellular penetration and/or metabolism, the nucleoside does not inhibit replication of a bicistron …

Detection of plasmid-mediated tigecycline-resistant gene tet(X4) in Escherichia coli from pork, Sichuan and Shandong Provinces, China, February 2019.

The plasmid-mediated high-level tigecycline resistance gene, tet(X4), was detected in seven Escherichia coli isolates from pork in two Chinese provinces. Two isolates belonged to the epidemic spreading sequence type ST101. Tet(X4) was adjacent to ISVsa3 and concurrent with floR in all seven isolates. In addition to IncFIB, the replicon IncFII was found to be linked to tet(X4). This report follows a recent detection of tet(X3)/(X4) in E. coli from animals and humans in China.

Comparative genomic characterization of publicly available human- and food-associated Aeromonas genomes from diverse countries.

Aeromonas spp. are emerging and neglected human pathogens widely distributed in nature. Despite their medical importance, the genomic characteristics of this genus remain incompletely understood. This study screened A. hydrophila (n = 63), A. veronii (n = 236), A. dhakensis (n = 78), and A. salmonicida (n = 13) genomes from strains isolated from human and food sources across 19 countries over a 42-year period for antimicrobial resistance, stress, and virulence genes, as well as plasmid replicons. Their genetic relatedness was assessed by searching single-nucleotide polymorphism (SNP) clusters,…

Whole-Genome Sequencing Reveals Heterogeneous Resistance Profiles and Selected Mobile Genetic Elements in Ecuadorian Clinical Enterobacter hormaechei subsp. xiangfangensis and subsp. hoffmannii.

Background:Enterobacter hormaechei, a member of the Enterobacter cloacae complex (ECC), is increasingly recognized as a multidrug-resistant (MDR) nosocomial pathogen. However, subspecies-level genomic data from Ecuador remain limited. Methods: Four clinical E. hormaechei isolates from a hospital in northern Ecuador were analyzed using antimicrobial susceptibility testing and whole-genome sequencing (WGS). Genomic characterization included multilocus sequence typing (MLST), resistome profiling, plasmid replicon detection, integron screening, genomic island analysis, and phylogenetic comparison …

Antimicrobial resistance and genetic diversity of Escherichia coli isolated from marine bivalves.

Escherichia coli can contaminate the marine environment through sewage and accumulate in bivalve molluscs. We assessed antimicrobial resista … l2 genes identified. Only one (1.5%) isolate had the intI integrase gene. Most isolates had the A/C replicon (73.9%) and belonged to phylogenetic group B1 (50.7%). PFGE analysis revealed the existence of 54 genotypes, with four clusters containing isolates from different sources. The presence of ESBL-producing strains, AMR genes, and diverse plasmid replic …

Phenotypic and genetic characterization of antimicrobial resistance in Salmonella enterica serovar Choleraesuis isolates from humans and animals in Spain from 2006 to 2021.

OBJECTIVES: While an increase in the levels of MDR in Salmonella enterica sevorar Choleraesuis has been reported in Europe, little is known … ntly higher number of antimicrobial resistance genes than human isolates, and often carried plasmid replicons of the IncHI2/IncHI2A type (42% of all animal isolates). In addition, we identified several MDR S. Choleraesuis strains circulating in humans and swine between 2006 and 2021. The phylogenetic analyses identified four clades associated with specific …

The dynamics of blaTEM resistance genes in Salmonella Typhi.

Salmonella Typhi (S. Typhi) is an important pathogen causing typhoid fever worldwide. The emergence of antibiotic resistance, including that … ying genetic contexts around blaTEM genes and GenoTyphi for determining genotypes, ARGs and plasmid replicons. We found that blaTEM-positive isolates occurred most commonly in specific location, especially in Asia and Africa and clustered among a limited number of genotypes. Flankophile identified 740 isolates (12.2%) with distinct flanking region patterns …

Для репликации генома требуется тромбинная декольте вируса гепатита Е в нескольких сохранённых местах.

Геномы вирусов РНК с положительной динамикой кодируют полипротеины, которые необходимы для мультипликации вирусов. Эти вирусные полипротеины должны подвергаться протеолизу (называемому также полипротеиновой переработкой) для создания функциональных белковых единиц. Этот протеолиз может осуществляться с помощью вирусно кодированных выступов, а также с помощью клеточных выступов, и, как правило, считается ключевым шагом в регулировании вирусного воспроизведения. Вирус гепатита Е (ГЭМ) является одной из главных причин острого вирусного гепатита. Положительный геном РНК переводится для создания по

Совпадение в аннотации оригинала
The genomes of positive-sense RNA viruses encode polyproteins that are essential for mediating viral replication. These viral polyproteins m … le in viral replication using a combination of in vitro translation experiments and HEV sub-genomic replicons. Our data suggest no evidence for a virally-encoded protease or auto-proteolytic activity, as in vitro translation predominantly generates unprocessed viral polyprotein precursors. However, seven cleavage sites within the polyprotein (suggested by …