chromosomal genes
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2021 ◽  
pp. 53-69
Author(s):  
Magdalena Anna Nowakowska

Escherichia coli is an important pathogen causing nosocomial infections. A significant problem in the treatment of infections caused by these microorganisms is their increasing resistance to β-lactam antibiotics, including third and fourth generation cephalosporins. The production of β-lactamases enzymes such as extended-spectrum β-lactamases (ESBLs) and AmpC β-lactamases is among the main mechanisms for resistance to third generation cephalosporins. The genes encoding AmpC cephalosporinases are chromosomal (cAmpC) or plasmid-mediated (pAmpC). In E. coli, the expression of the ampC genes may be conditioned by the constitutive expression of low level ampC chromosomal genes. These strains remain susceptible to β-lactam antibiotics. However, mutations in the promoter region of the ampC may result in increased level of expression of chromosomal ampC genes. This can leads to resistance to cephalosporins. Resistance to cephalosporins in E. coli can be also associated with plasmid-mediated AmpC β−lactamases (pAmpC). In E. coli the presence of one or more plasmid-mediated AmpC β−lactamases along with the neglible expression of chromosomal encoded AmpC enzyme can leads to resistance to broad-spectrum cephalosporins. This review is focused on a resistance mechanisms associated with the production of AmpC cephalosporinases in clinical E. coli isolates.


Author(s):  
Jerónimo Rodríguez-Beltrán ◽  
Ricardo León-Sampedro ◽  
Paula Ramiro-Martínez ◽  
Carmen de la Vega ◽  
Fernando Baquero ◽  
...  

Plasmids are key drivers of bacterial evolution because they are crucial agents for the horizontal transfer of adaptive traits, such as antibiotic resistance. Most plasmids entail a metabolic burden that reduces the fitness of their host if there is no selection for plasmid-encoded genes. It has been hypothesized that the translational demand imposed by plasmid-encoded genes is a major mechanism driving the fitness cost of plasmids. Plasmid-encoded genes typically present a different codon usage from host chromosomal genes. As a consequence, the translation of plasmid-encoded genes might sequestrate ribosomes on plasmid transcripts, overwhelming the translation machinery of the cell. However, the pervasiveness and origins of the translation-derived costs of plasmids are yet to be assessed. Here, we systematically altered translation efficiency in the host cell to disentangle the fitness effects produced by six natural antibiotic resistance plasmids. We show that limiting translation efficiency either by reducing the number of available ribosomes or their processivity does not increase plasmid costs. Overall, our results suggest that ribosomal paucity is not a major contributor to plasmid fitness costs. This article is part of the theme issue ‘The secret lives of microbial mobile genetic elements’.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Suzanne Humphrey ◽  
Alfred Fillol-Salom ◽  
Nuria Quiles-Puchalt ◽  
Rodrigo Ibarra-Chávez ◽  
Andreas F. Haag ◽  
...  

AbstractIt is commonly assumed that the horizontal transfer of most bacterial chromosomal genes is limited, in contrast to the frequent transfer observed for typical mobile genetic elements. However, this view has been recently challenged by the discovery of lateral transduction in Staphylococcus aureus, where temperate phages can drive the transfer of large chromosomal regions at extremely high frequencies. Here, we analyse previously published as well as new datasets to compare horizontal gene transfer rates mediated by different mechanisms in S. aureus and Salmonella enterica. We find that the horizontal transfer of core chromosomal genes via lateral transduction can be more efficient than the transfer of classical mobile genetic elements via conjugation or generalized transduction. These results raise questions about our definition of mobile genetic elements, and the potential roles played by lateral transduction in bacterial evolution.


2021 ◽  
Author(s):  
Melis A Aksit ◽  
Bo Yu ◽  
Bernard AJ Roelen ◽  
Barbara R. Migeon

ABSTRACTX inactivation is the means of equalizing the dosage of X chromosomal genes in male and female eutherian mammals, so that only one X is active in each cell. The XIST locus (in cis) on each additional X chromosome initiates the transcriptional silencing of that chromosome, making it an inactive X. How the active X in both males and females is protected from inactivation by its own XIST locus is not well understood in any mammal. Previous studies of autosomal duplications suggest that gene(s) on the short arm of human chromosome 19 repress XIST function on the active X. Here, we examine the time of transcription of some candidate genes in preimplantation embryos using single-cell RNA sequencing data from human embryos and qRT-PCR from bovine embryos. The candidate genes assayed are those transcribed from 19p13.3-13.2, which are widely expressed and can remodel chromatin. Our results confirm that XIST is expressed at low levels from the future active X in embryos of both sexes; they also show that the XIST locus is repressed in both sexes when pluripotency factors are being upregulated, during the 4-8 cell and morula stages in human and bovine embryos – well before the early blastocyst (E5) when XIST on the inactive X in females begins to be upregulated. Our data suggest a role for DNMT1, UHRF1, SAFB and SAFB2 in XIST repression; they also exclude XACT and other 19p candidate genes and provide the transcriptional timing for some genes not previously assayed in human or bovine preimplantation embryos.


2021 ◽  
Vol 22 (14) ◽  
pp. 7499
Author(s):  
Benjamin Leyton ◽  
Juliana Nunes Ramos ◽  
Paulo Victor Pereira Baio ◽  
João Flávio Carneiro Veras ◽  
Cassius Souza ◽  
...  

Corynebacterium striatum, a bacterium that is part of the normal skin microbiota, is also an opportunistic pathogen. In recent years, reports of infections and in-hospital and nosocomial outbreaks caused by antimicrobial multidrug-resistant C. striatum strains have been increasing worldwide. However, there are no studies about the genomic determinants related to antimicrobial resistance in C. striatum. This review updates global information related to antimicrobial resistance found in C. striatum and highlights the essential genomic aspects in its persistence and dissemination. The resistome of C. striatum comprises chromosomal and acquired elements. Resistance to fluoroquinolones and daptomycin are due to mutations in chromosomal genes. Conversely, resistance to macrolides, tetracyclines, phenicols, beta-lactams, and aminoglycosides are associated with mobile genomic elements such as plasmids and transposons. The presence and diversity of insertion sequences suggest an essential role in the expression of antimicrobial resistance genes (ARGs) in genomic rearrangements and their potential to transfer these elements to other pathogens. The present study underlines that the resistome of C. striatum is dynamic; it is in evident expansion and could be acting as a reservoir for ARGs.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Oriana Genolet ◽  
Anna A. Monaco ◽  
Ilona Dunkel ◽  
Michael Boettcher ◽  
Edda G. Schulz

Abstract Background X-chromosomal genes contribute to sex differences, in particular during early development, when both X chromosomes are active in females. Double X-dosage shifts female pluripotent cells towards the naive stem cell state by increasing pluripotency factor expression, inhibiting the differentiation-promoting MAP kinase (MAPK) signaling pathway, and delaying differentiation. Results To identify the genetic basis of these sex differences, we use a two-step CRISPR screening approach to comprehensively identify X-linked genes that cause the female pluripotency phenotype in murine embryonic stem cells. A primary chromosome-wide CRISPR knockout screen and three secondary screens assaying for different aspects of the female pluripotency phenotype allow us to uncover multiple genes that act in concert and to disentangle their relative roles. Among them, we identify Dusp9 and Klhl13 as two central players. While Dusp9 mainly affects MAPK pathway intermediates, Klhl13 promotes pluripotency factor expression and delays differentiation, with both factors jointly repressing MAPK target gene expression. Conclusions Here, we elucidate the mechanisms that drive sex-induced differences in pluripotent cells and our approach serves as a blueprint to discover the genetic basis of the phenotypic consequences of other chromosomal effects.


Author(s):  
Yi Zhang ◽  
Tao Wang ◽  
Yan Wang ◽  
Kun Xia ◽  
Jinchen Li ◽  
...  

AbstractNeurodevelopmental disorders (NDDs) are a group of diseases characterized by high heterogeneity and frequently co-occurring symptoms. The mutational spectrum in patients with NDDs is largely incomplete. Here, we sequenced 547 genes from 1102 patients with NDDs and validated 1271 potential functional variants, including 108 de novo variants (DNVs) in 78 autosomal genes and seven inherited hemizygous variants in six X chromosomal genes. Notably, 36 of these 78 genes are the first to be reported in Chinese patients with NDDs. By integrating our genetic data with public data, we prioritized 212 NDD candidate genes with FDR < 0.1, including 17 novel genes. The novel candidate genes interacted or were co-expressed with known candidate genes, forming a functional network involved in known pathways. We highlighted MSL2, which carried two de novo protein-truncating variants (p.L192Vfs*3 and p.S486Ifs*11) and was frequently connected with known candidate genes. This study provides the mutational spectrum of NDDs in China and prioritizes 212 NDD candidate genes for further functional validation and genetic counseling.


Open Biology ◽  
2021 ◽  
Vol 11 (4) ◽  
Author(s):  
Lisa Uehara ◽  
Shigeaki Saitoh ◽  
Ayaka Mori ◽  
Kenichi Sajiki ◽  
Yusuke Toyoda ◽  
...  

Mitochondria are essential for regulation of cellular respiration, energy production, small molecule metabolism, anti-oxidation and cell ageing, among other things. While the mitochondrial genome contains a small number of protein-coding genes, the great majority of mitochondrial proteins are encoded by chromosomal genes. In the fission yeast Schizosaccharomyces pombe , 770 proteins encoded by chromosomal genes are located in mitochondria. Of these, 195 proteins, many of which are implicated in translation and transport, are absolutely essential for viability. We isolated and characterized eight temperature-sensitive ( ts ) strains with mutations in essential mitochondrial proteins. Interestingly, they are also sensitive to limited nutrition (glucose and/or nitrogen), producing low-glucose-sensitive and ‘super-housekeeping' phenotypes. They fail to produce colonies under low-glucose conditions at the permissive temperature or lose cell viability under nitrogen starvation at the restrictive temperature. The majority of these ts mitochondrial mutations may cause defects of gene expression in the mitochondrial genome. mrp4 and mrp17 are defective in mitochondrial ribosomal proteins. ppr3 is defective in rRNA expression, and trz2 and vrs2 are defective in tRNA maturation. This study promises potentially large dividends because mitochondrial quiescent functions are vital for human brain and muscle, and also for longevity.


Author(s):  
T. I. Stetsko

In the article a literature review of scientific papers on the topic of antimicrobial resistance of bacteria of the family Pasteurellaceae, pathogens of respiratory diseases in pigs and cattle, is presented. The main mechanisms of the development of Pasteurellaceae resistance to β-lactam antibiotics are the synthesis of β-lactamases by bacteria, what are able to break the beta-lactam ring, thereby inactivating β-lactams, or alteration of the penicillin-binding proteins structure. Other mechanisms, such as reduced permeability of the outer membrane or the process of active removal of antibiotics from the bacterial cell (efflux), are very rare. Resistance among Pasteurellaceae to β-lactams is often associated with plasmids. Eflux and ribosomal protection are the main mechanisms for the development of resistance of Pasteurellaceae to tetracyclines. At least nine tetracycline resistance genes (tet genes) have been identified in bacteria of the genus Pasteurella, Mannheimia, Actinobacillus and Haemophilus, what encode these processes. Resistance to aminoglycosides and aminocyclitols is mainly caused by enzymatic inactivation of antibiotics, as well as through mutations in chromosomal genes. Many plasmids carry genes of resistance to aminoglycosides, causing resistance to antibiotics of other groups. Chemical modification of a ribosomal target by rRNA methylases and mutations in ribosomal proteins are the main resistance mechanisms of bacteria of the family Pasteurellaceae to macrolides. Many gram-negative bacteria have a natural resistance to macrolide antibiotics. The development of lincosamide resistance is influenced by methyltransferase 23S rRNA, active efflux proteins, enzymatic inactivation and chromosomal mutations. Resistance of bacteria of the family Pasteurellaceae to chloramphenicol is caused mainly by enzymatic inactivation, while the emergence of resistance to fluorophenicol is associated with the efflux of an antibiotic from a bacterial cell. Plasmids carrying phenicol resistance genes were detected in isolates of P. multocida, M. haemolytica, A. pleuropneumoniae and H. parasuis. Usually the level of bacteria sensitivity of the genus Pasteurella, Mannheimia, Actinobacillus and Haemophilus to quinolones is quite high. Resistance to quinolones mainly occurs due to mutational alterations in chromosomal genes, and may also be in consequence of the export antibiotics from the cell by membrane proteins or thanks to qnr genes of plasmids. The main mechanism of resistance to sulfonamides and trimethoprim is both plasmid-mediated and mutation-induced production of altered dihydropteroate synthetase and dihydrofolate reductase with reduced affinity with these antimicrobials. Monitoring of antibiotic resistance with the determination of its mechanism phenomenon will facilitate the choice of an effective agent of etiotropic therapy of respiratory diseases of cattle and pigs caused by bacteria of the family Pasteurellaceae.


2021 ◽  
Author(s):  
Yi Zhang ◽  
Tao Wang ◽  
Yan Wang ◽  
Kun Xia ◽  
Jinchen Li ◽  
...  

Abstract Neurodevelopmental disorders (NDDs) are a group of diseases characterized by highly heterogeneity and frequently co-occur symptoms. The mutational spectrum in patients with NDDs is largely incomplete. Here, we sequenced 547 genes from 1,102 patients with NDDs and validated 1,271 potential functional variants, including 108 de novo variants (DNVs) in 78 autosomal genes and seven inherited hemizygous variants in six X chromosomal genes. Notably, 36 of these 78 genes are the first to be reported in Chinese patients with NDDs. By integrating our genetic data with public data, we prioritised 212 NDD candidate genes with FDR < 0.1, including 17 novel genes. The novel candidate genes interacted or were co-expressed with known candidate genes, forming a functional network involved in known pathways. We highlighted MSL2, which carried two de novo protein-truncating variants (p.L192Vfs*3 and p.S486Ifs*11) and was most frequently connected with known candidate genes. This study provides the mutational spectrum of NDDs in China and prioritises 212 NDD candidate genes for further functional validation and genetic counseling.


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