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Extended-spectrum ß-lactamases (ESBLs) production and (fluoro)quinolone (FQ) resistance among Salmonella pose a public health threat. The objective of this study was the phenotypic and genotypic characterization of an ESBL-producing and nalidixic acid-resistant Salmonella enterica serovar Gloucester isolate (serotype 4:i:l,w) of sequence type 34 (ST34) from ready-to-eat (RTE) meat products in China. Whole-genome short and long read sequencing (HiSeq and MinION) results showed that it contained bla CTX-M- 55, qnrS1, and tetB genes, with bla CTX-M- 55 and qnrS1 located in chromosomal IS26-mediated composite transposon (IS26-qnrS1-IS3-Tn3-orf-bla CTX-M- 55-ISEcp1-IS26). The same genetic structure was found in the chromosome of S. enterica subsp. enterica serovar Typhimurium strain and in several plasmids of Escherichia coli, indicating that the IS26-mediated composite transposon in the chromosome of S. Gloucester may originate from plasmids of E. coli and possess the ability to disseminate to Salmonella and other bacterial species. Besides, the structural unit qnrS1-IS3-Tn3-orf-bla CTX-M- 55 was also observed to be linked with ISKpn19 in both the chromosomes and plasmids of various bacteria species, highlighting the contribution of the insertion sequences (IS26 and ISKpn19) to the co-dissemination of bla CTX-M- 55 and qnrS1. To our knowledge, this is the first description of chromosomal bla CTX-M- 55 and qnrS in S. Gloucester from RTE meat products. Our work expands the host range and provides additional evidence of the co-transfer of bla CTX-M- 55 and qnrS1 among different species of Salmonella through the food chain.
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[This corrects the article DOI: 10.3389/fmicb.2021.646101.].
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Salmonella enterica displaying resistance to extended-spectrum cephalosporins and fluoroquinolone (FQs) has been deemed a high-priority pathogen by the World Health Organization (WHO). While CTX-M type acquired ß-lactamases have been detected in S. enterica serovar Bovismorbificans, DHA enzymes have been rarely reported in S. Bovismorbificans. In this study, we here report for the first time the isolation of two multi-drug resistant (MDR) S. Bovismorbificans strains co-harboring plasmid-encoded AmpC (pAmpC) ß-lactamase gene (blaDHA-1) and qnrB gene, 16Sal017 isolated from a chicken meat sample and 16Sal018 from a grass carp fish sample, collected from retail markets in Guangzhou, China. The blaDHA-1 and qnrB genes in these two strains were both located on the same novel 217,773 bp IncHI2 plasmid belonged to ST2. The plasmid contained 16 additional acquired antimicrobial resistance genes encoding resistance to eight antibiotic classes and quaternary ammonium compound. Besides, 16Sal017 contained an additional 10,124 bp Col (pHAD28)-like plasmid harboring qnrS1. The blaDHA-1 and qnrB4 genes were located in an 18,198 bp region, sul1-qacEΔ1-ampR-blaDHA-1-pspABCDF-qnrB4-sapABC-IS91-sul1-qacEΔ1, which has been identified in various bacteria species, indicating the high transfer ability of blaDHA-1 and qnrB4 genes within this gene cluster. The IncHI2 plasmid was found to be transferable to Escherichia coli J53 by conjugation and resulted in the acquiring of multiple resistance in the transconjugants. Genome sequence comparisons by cgMLST and MAUVE alignment indicated 16Sal017 and 16Sal018 are highly similar and are not epidemiologically linked with strains from other sources and countries. Our findings suggest S. Bovismorbificans as a new host for conjugative mega-plasmid harboring blaDHA-1 and qnrB4 genes, and highlight the potential transmission opportunity of these S. Bovismorbificans clones through the food chain, which need continuous investigation.
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Salmonella enterica , Salmonella , Animales , Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Pruebas de Sensibilidad Microbiana , Plásmidos/genética , Salmonella enterica/genética , Serogrupo , beta-Lactamasas/genéticaRESUMEN
Kidney function depends on the nephron, which comprises a blood filter, a tubule that is subdivided into functionally distinct segments, and a collecting duct. How these regions arise during development is poorly understood. The zebrafish pronephros consists of two linear nephrons that develop from the intermediate mesoderm along the length of the trunk. Here we show that, contrary to current dogma, these nephrons possess multiple proximal and distal tubule domains that resemble the organization of the mammalian nephron. We examined whether pronephric segmentation is mediated by retinoic acid (RA) and the caudal (cdx) transcription factors, which are known regulators of segmental identity during development. Inhibition of RA signaling resulted in a loss of the proximal segments and an expansion of the distal segments, while exogenous RA treatment induced proximal segment fates at the expense of distal fates. Loss of cdx function caused abrogation of distal segments, a posterior shift in the position of the pronephros, and alterations in the expression boundaries of raldh2 and cyp26a1, which encode enzymes that synthesize and degrade RA, respectively. These results suggest that the cdx genes act to localize the activity of RA along the axis, thereby determining where the pronephros forms. Consistent with this, the pronephric-positioning defect and the loss of distal tubule fate were rescued in embryos doubly-deficient for cdx and RA. These findings reveal a novel link between the RA and cdx pathways and provide a model for how pronephric nephrons are segmented and positioned along the embryonic axis.
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Regulación del Desarrollo de la Expresión Génica , Regulación de la Expresión Génica , Riñón/embriología , Tretinoina/metabolismo , Animales , Clonación Molecular , Proteínas de Homeodominio/metabolismo , Hibridación in Situ , Ratones , Modelos Biológicos , Mutación , Fenotipo , Estructura Terciaria de Proteína , Factores de Transcripción/metabolismo , Pez CebraRESUMEN
The zebrafish is emerging as a prominent model system for studying the genetics of human development and disease. Genetic alterations that underlie each mutant model can exist in the form of single base changes, balanced chromosomal rearrangements, or genetic imbalances. To detect genetic imbalances in an unbiased genome-wide fashion, array comparative genomic hybridization (CGH) can be used. We have developed a 5-Mb resolution array CGH platform specifically for the zebrafish. This platform contains 286 bacterial artificial chromosome (BAC) clones, enriched for orthologous sequences of human oncogenes and tumor suppressor genes. Each BAC clone has been end-sequenced and cytogenetically assigned to a specific location within the zebrafish genome, allowing for ease of integration of array CGH data with the current version of the genome assembly. This platform has been applied to three zebrafish cancer models. Significant genomic imbalances were detected in each model, identifying different regions that may potentially play a role in tumorigenesis. Hence, this platform should be a useful resource for genetic dissection of additional zebrafish developmental and disease models as well as a benchmark for future array CGH platform development.
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Hibridación Genómica Comparativa/métodos , Genes Supresores de Tumor , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Oncogenes , Pez Cebra/genética , Animales , Animales Modificados Genéticamente , Cromosomas Artificiales Bacterianos , Modelos Animales de Enfermedad , Humanos , Hibridación Fluorescente in Situ , Melanoma/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Reproducibilidad de los Resultados , Rabdomiosarcoma/genética , Pez Cebra/metabolismoRESUMEN
The initiation of cellular programs is orchestrated by key transcription factors and chromatin regulators that activate or inhibit target gene expression. To generate a compendium of chromatin factors that establish the epigenetic code during developmental haematopoiesis, a large-scale reverse genetic screen was conducted targeting orthologues of 425 human chromatin factors in zebrafish. A set of chromatin regulators was identified that target different stages of primitive and definitive blood formation, including factors not previously implicated in haematopoiesis. We identified 15 factors that regulate development of primitive erythroid progenitors and 29 factors that regulate development of definitive haematopoietic stem and progenitor cells. These chromatin factors are associated with SWI/SNF and ISWI chromatin remodelling, SET1 methyltransferase, CBP-p300-HBO1-NuA4 acetyltransferase, HDAC-NuRD deacetylase, and Polycomb repressive complexes. Our work provides a comprehensive view of how specific chromatin factors and their associated complexes play a major role in the establishment of haematopoietic cells in vivo.