A fine-scale map of genome-wide recombination in divergent Escherichia coli population

2020 ◽  
Author(s):  
Yu Kang ◽  
Lina Yuan ◽  
Xing Shi ◽  
Yanan Chu ◽  
Zilong He ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Critical Role ◽  
Prokaryotic Genome ◽  
Ecological Niches ◽  
Phylogenetic Distance ◽  
Fine Scale ◽  
Ecological Fitness ◽  
Genome Wide

Abstract Recombination is one of the most important molecular mechanisms of prokaryotic genome evolution, but its exact roles are still in debate. Here we try to infer genome-wide recombination within a species, utilizing a dataset of 149 complete genomes of Escherichia coli from diverse animal hosts and geographic origins, including 45 in-house sequenced with the single-molecular real-time platform. Two major clades identified based on physiological, clinical and ecological characteristics form distinct genetic lineages based on scarcity of interclade gene exchanges. By defining gene-based syntenies for genomic segments within and between the two clades, we build a fine-scale recombination map for this representative global E. coli population. The map suggests extensive within-clade recombination that often breaks physical linkages among individual genes but seldom interrupts the structure of genome organizational frameworks as well as primary metabolic portfolios supported by the framework integrity, possibly due to strong natural selection for both physiological compatibility and ecological fitness. In contrast, the between-clade recombination declines drastically when phylogenetic distance increases to the extent where a 10-fold reduction can be observed, establishing a firm genetic barrier between clades. Our empirical data suggest a critical role for such recombination events in the early stage of speciation where recombination rate is associated with phylogenetic distance in addition to sequence and gene variations. The extensive intraclade recombination binds sister strains into a quasisexual group and optimizes genes or alleles to streamline physiological activities, whereas the sharply declined interclade recombination split the population into clades adaptive to divergent ecological niches.

scholarly journals Gene-centric intra- and inter-clade recombination in a context ofEsche-richia colisubpopulations

2017 ◽  
Author(s):  
Yu Kang ◽  
Xing Shi ◽  
Lina Yuan ◽  
Yanan Chu ◽  
Fei Chen ◽  
...  
Keyword(s):  
Early Stage ◽  
Critical Role ◽  
Ecological Niches ◽  
Phylogenetic Distance ◽  
Bacterial Genomes ◽  
Genetic Barrier ◽  
Ecological Fitness ◽  
E Coli ◽  
Genome Wide ◽  
Species Evolution

ABSTRACTRecombination is one of the most important mechanisms of prokaryotic species evolution but its exact roles are still in debate. Here we try to infer genome-wide recombination events within a species uti-lizing a dataset of 104 complete genomes ofEscherichia colifrom diverse origins, among which 45 from world-wide animal-hosts are in-house sequenced using SMRT (single-molecular real time) technology.Two major clades are identified based on evidences of ecological and physiological characteristics, as well as distinct genomic features implying scarce inter-clade genetic exchange. By comparing the synteny of identical fragments genome-widely searched for each genome pair, we achieve a fine-scale map of re-combination within the population. The recombination is rather extensive within clade, which is able to break linkages between genes but does not interrupt core genome framework and primary metabolic port-folios possibly due to natural selection for physiological compatibility and ecological fitness. Meanwhile,the recombination between clades declines drastically as the phylogenetic distance increases, generally 10-fold reduced than those of the intra-clade, which establishes genetic barrier between clades. These empirical data of recombination suggest its critical role in the early stage of speciation, where recombina-tion rate differs according to phylogentic distance. The extensive intra-clade recombination coheres sister strains into a quasi-sexual group and optimizes genes or alleles to streamline physiological activities,whereas shapely declined inter-clade recombination split the population into clades adaptive to divergent ecological niches.Significance StatementRoles of recombination in species evolution have been debated for decades due to difficulties in inferring recombination events during the early stage of speciation, especially when recombination is always complicated by frequent gene transfer events of bacterial genomes. Based on 104 high-quality completeE. coligenomes, we infer gene-centric dynamics of recombination in the formation of twoE. coliclades or subpopulations, and recombination is found to be rather intensive in a within-clade fashion, which forces them to be quasi-sexual. The recombination events can be mapped among individual genomes in the context of genes and their variations; decreased between-clade and increased intra-claderecombination engender a genetic barrier that further encourages clade-specific secondary metabolic portfolios for better environmental adaptation. Recombination is thus a major force that accelerates bacterial evolution to fit ecological diversity.

Sequence of Colonization Determines the Composition of Mixed Biofilms by Escherichia coli O157:H7 and O111:H8 Strains†

2015 ◽  
Vol 78 (8) ◽  
pp. 1554-1559 ◽  
Author(s):  
RONG WANG ◽  
NORASAK KALCHAYANAND ◽  
JAMES L. BONO
Keyword(s):  
Escherichia Coli ◽  
Foodborne Pathogens ◽  
Early Stage ◽  
Critical Role ◽  
The United States ◽  
Food Samples ◽  
E Coli ◽  
Cell Percentage ◽  
Composition And Structure ◽  
Biofilm Development

Bacterial biofilms are one of the potential sources of cross-contamination in food processing environments. Shiga toxin–producing Escherichia coli (STEC) O157:H7 and O111:H8 are important foodborne pathogens capable of forming biofilms, and the coexistence of these two STEC serotypes has been detected in various food samples and in multiple commercial meat plants throughout the United States. Here, we investigated how the coexistence of these two STEC serotypes and their sequence of colonization could affect bacterial growth competition and mixed biofilm development. Our data showed that E. coli O157:H7 strains were able to maintain a higher cell percentage in mixed biofilms with the co-inoculated O111:H8 companion strains, even though the results of planktonic growth competition were strain dependent. On solid surfaces with preexisting biofilms, the sequence of colonization played a critical role in determining the composition of the mixed biofilms because early stage precolonization significantly affected the competition results between the E. coli O157:H7 and O111:H8 strains. The precolonizer of either serotype was able to outgrow the other serotype in both planktonic and biofilm phases. The competitive interactions among the various STEC serotypes would determine the composition and structure of the mixed biofilms as well as their potential risks to food safety and public health, which is largely influenced by the dominant strains in the mixtures. Thus, the analysis of mixed biofilms under various conditions would be of importance to determine the nature of mixed biofilms composed of multiple microorganisms and to help implement the most effective disinfection operations accordingly.

scholarly journals Convergent Molecular Evolution of Genomic Cores in Salmonella enterica and Escherichia coli

2012 ◽  
Vol 194 (18) ◽  
pp. 5002-5011 ◽  
Author(s):  
Sujay Chattopadhyay ◽  
Sandip Paul ◽  
Dagmara I. Kisiela ◽  
Elena V. Linardopoulou ◽  
Evgeni V. Sokurenko
Keyword(s):  
Escherichia Coli ◽  
Molecular Evolution ◽  
Salmonella Enterica ◽  
Molecular Mechanisms ◽  
Hot Spot ◽  
Content Type ◽  
Adaptive Mutations ◽  
Genome Wide ◽  
Evolution Of Proteins ◽  
Core Genes

ABSTRACTOne of the strongest signals of adaptive molecular evolution of proteins is the occurrence of convergent hot spot mutations: repeated changes in the same amino acid positions. We performed a comparative genome-wide analysis of mutation-driven evolution of core (omnipresent) genes in 17 strains ofSalmonella entericasubspecies I and 22 strains ofEscherichia coli. More than 20% of core genes in bothSalmonellaandE. coliaccumulated hot spot mutations, with a predominance of identical changes having recent evolutionary origin. There is a significant overlap in the functional categories of the adaptively evolving genes in both species, although mostly via separate molecular mechanisms. As a strong evidence of the link between adaptive mutations and virulence inSalmonella, two human-restricted serovars, Typhi and Paratyphi A, shared the highest number of genes with serovar-specific hot spot mutations. Many of the core genes affected by Typhi/Paratyphi A-specific mutations have known virulence functions. For each species, a list of nonrecombinant core genes (and the hot spot mutations therein) under positive selection is provided.

scholarly journals Systematic exploration of Escherichia coli phage–host interactions with the BASEL phage collection

PLoS Biology ◽  
2021 ◽  
Vol 19 (11) ◽  
pp. e3001424
Author(s):  
Enea Maffei ◽  
Aisylu Shaidullina ◽  
Marco Burkolter ◽  
Yannik Heyer ◽  
Fabienne Estermann ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Bacterial Infections ◽  
Molecular Mechanisms ◽  
Model Systems ◽  
Host Recognition ◽  
Ecological Niches ◽  
Traditional Model ◽  
Host Interactions ◽  
Trade Offs ◽  
Systematic Exploration

Bacteriophages, the viruses infecting bacteria, hold great potential for the treatment of multidrug-resistant bacterial infections and other applications due to their unparalleled diversity and recent breakthroughs in their genetic engineering. However, fundamental knowledge of the molecular mechanisms underlying phage–host interactions is mostly confined to a few traditional model systems and did not keep pace with the recent massive expansion of the field. The true potential of molecular biology encoded by these viruses has therefore remained largely untapped, and phages for therapy or other applications are often still selected empirically. We therefore sought to promote a systematic exploration of phage–host interactions by composing a well-assorted library of 68 newly isolated phages infecting the model organism Escherichia coli that we share with the community as the BASEL (BActeriophage SElection for your Laboratory) collection. This collection is largely representative of natural E. coli phage diversity and was intensively characterized phenotypically and genomically alongside 10 well-studied traditional model phages. We experimentally determined essential host receptors of all phages, quantified their sensitivity to 11 defense systems across different layers of bacterial immunity, and matched these results to the phages’ host range across a panel of pathogenic enterobacterial strains. Clear patterns in the distribution of phage phenotypes and genomic features highlighted systematic differences in the potency of different immunity systems and suggested the molecular basis of receptor specificity in several phage groups. Our results also indicate strong trade-offs between fitness traits like broad host recognition and resistance to bacterial immunity that might drive the divergent adaptation of different phage groups to specific ecological niches. We envision that the BASEL collection will inspire future work exploring the biology of bacteriophages and their hosts by facilitating the discovery of underlying molecular mechanisms as the basis for an effective translation into biotechnology or therapeutic applications.

scholarly journals Escherichia coli Gene Expression Responsive to Levels of the Response Regulator EvgA

2002 ◽  
Vol 184 (22) ◽  
pp. 6225-6234 ◽  
Author(s):  
Nobuhisa Masuda ◽  
George M. Church
Keyword(s):  
Escherichia Coli ◽  
Multidrug Resistance ◽  
Stationary Phase ◽  
Deletion Mutant ◽  
Efflux Pump ◽  
Response Regulator ◽  
Critical Role ◽  
Acid Resistance ◽  
Oligonucleotide Microarrays ◽  
Genome Wide

ABSTRACT To investigate the function of the EvgA response regulator, we compared the genome-wide transcription profile of EvgA-overexpressing and EvgA-lacking Escherichia coli strains by oligonucleotide microarrays. The microarray measurements allowed the identification of at least 37 EvgA-activated genes, including acid resistance-related genes gadABC and hdeAB, efflux pump genes yhiUV and emrK, and 21 genes with unknown function. EvgA overexpression conferred acid resistance to exponentially growing cells. This acid resistance was abolished by deletion of ydeP, ydeO, or yhiE, which was induced by EvgA overexpression. These results suggest that ydeP, ydeO, and yhiE are novel genes related to acid resistance and that EvgA regulates several acid resistance genes. Furthermore, the deletion of yhiE completely abolished acid resistance in stationary-phase cells, suggesting that YhiE plays a critical role in stationary-phase acid resistance. The multidrug resistance in an acrB deletion mutant caused by EvgA overexpression was completely abolished by deletion of yhiUV, while the emrKY deletion had no effect on the increase in resistance by EvgA overexpression. In addition, EvgA overexpression did not confer resistance in a tolC-deficient strain. These results suggest that YhiUV induced by EvgA overexpression is functionally associated with TolC and contributes to multidrug resistance.

scholarly journals Novel Isoquinoline Alkaloid Litcubanine A - A Potential Anti-Inflammatory Candidate

2021 ◽  
Vol 12 ◽  
Author(s):  
Huan Xia ◽  
Yitong Liu ◽  
Guiyang Xia ◽  
Yi Liu ◽  
Sheng Lin ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Early Stage ◽  
Critical Role ◽  
Isoquinoline Alkaloid ◽  
Inflammatory Factors ◽  
Skin Wound Healing ◽  
Anti Inflammatory ◽  
Inflammatory Macrophages

Macrophages play a critical role in innate and adaptive immunity, and the regulation of macrophage function in inflammatory disease treatment has been widely studied. Litsea cubeba is an important Chinese medicinal plant used for the treatment of inflammatory diseases. However, the inflammatory bioactive ingredients in L. cubeba and underlying molecular mechanisms are poorly understood. Herein, we first obtained and elucidated a novel isoquinoline alkaloid, Litcubanine A (LA), from L. cubeba. An in vitro study indicated that LA could significantly inhibit LPS-induced activation of inflammatory macrophages via the NF-κB pathway, leading to the decrease of inflammatory factors including iNOS, TNF-α, and IL-1β. Moreover, LA showed an inhibiting effect on the expression of NO in macrophages by directly binding to iNOS protein. Molecular simulation docking also demonstrated that active LA created an interaction with GLU 371 residue of iNOS via attractive charge derived from the N→O group, revealing its highly selective inhibition toward iNOS. By using the IκK inhibitor and iNOS inhibitor, these two regulatory targets of LA on inflammatory macrophages were verified in vitro. Finally, by using a caudal fin resection model in zebrafish larvae, and the skin wound healing model in mice, we proved in vivo that LA down-regulated the secretion of local inflammatory factors by inhibiting macrophage recruitment and activation at the early stage of the injury. Collectively, our study demonstrated that the novel isoquinoline alkaloid LA suppresses LPS-induced activation of inflammatory macrophages by modulating the NF-κB pathway, suggesting that inflammatory macrophage activation pathway is an effective target for inflammation treatment, and LA is a new pharmacophore for the development of novel and effective anti-inflammatory agents to regulate local macrophages.

scholarly journals FACT maintains pluripotency factor expression through gene-distal regulation in embryonic stem cells

2021 ◽  
Author(s):  
David C Klein ◽  
Santana M Lardo ◽  
Sarah J Hainer
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Molecular Mechanisms ◽  
Nucleosome Occupancy ◽  
Critical Role ◽  
Embryonic Stem ◽  
Putative Gene ◽  
Cell Fate Decisions ◽  
Genome Wide

The mammalian FACT complex is a highly conserved histone chaperone with essential roles in transcription elongation, histone deposition, and maintenance of stem cell state. FACT is essential for viability in pluripotent cells and cancer cells, but otherwise dispensable for most mammalian cell types. FACT deletion or inhibition can block reprogramming of fibroblasts to induced pluripotent stem cells, yet the molecular mechanisms through which FACT regulates cell fate decisions remain unclear. To determine the mechanism by which FACT regulates stem cell identity, we used the auxin-inducible degron systems to deplete murine embryonic stem cells of FACT subunit SPT16 and subjected depleted cells to genome-wide factor localization, nascent transcription analyses, and genome-wide nucleosome profiling. Inducible depletion of SPT16 reveals a critical role in regulating targets of the master regulators of pluripotency: OCT4, KLF4, MYC, NANOG, and SOX2. Depletion of SPT16 leads to increased nucleosome occupancy at genomic loci occupied by these transcription factors, as well as gene-distal regulatory sites defined by DNaseI hypersensitivity. This heightened occupancy suggests a mechanism of nucleosome filling, wherein the sites typically maintained in an accessible state by FACT are occluded through loss of FACT-regulated nucleosome spacing. 20% of transcription arising from gene-distal regions bound by these factors is directly dependent on FACT, and putative gene targets of these non-coding RNAs are highly enriched for pluripotency in pathway analyses. Upon FACT depletion, transcription of Pou5f1 (OCT4), Sox2, and Nanog are downregulated, suggesting that FACT not only co-regulates expression of the encoded proteins' targets, but also the pluripotency factors themselves. We find that FACT maintains cellular pluripotency through a complex regulatory network of both coding and non-coding transcription.

scholarly journals Genome-wide identification of CCA1 targets uncovers an expanded clock network in Arabidopsis

2015 ◽  
Vol 112 (34) ◽  
pp. E4802-E4810 ◽  
Author(s):  
Dawn H. Nagel ◽  
Colleen J. Doherty ◽  
Jose L. Pruneda-Paz ◽  
Robert J. Schmitz ◽  
Joseph R. Ecker ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Stress Responses ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Critical Role ◽  
Gene Promoters ◽  
Biological Processes ◽  
Functional Studies ◽  
Genome Wide ◽  
Genomic Regions

The circadian clock in Arabidopsis exerts a critical role in timing multiple biological processes and stress responses through the regulation of up to 80% of the transcriptome. As a key component of the clock, the Myb-like transcription factor CIRCADIAN CLOCK ASSOCIATED1 (CCA1) is able to initiate and set the phase of clock-controlled rhythms and has been shown to regulate gene expression by binding directly to the evening element (EE) motif found in target gene promoters. However, the precise molecular mechanisms underlying clock regulation of the rhythmic transcriptome, specifically how clock components connect to clock output pathways, is poorly understood. In this study, using ChIP followed by deep sequencing of CCA1 in constant light (LL) and diel (LD) conditions, more than 1,000 genomic regions occupied by CCA1 were identified. CCA1 targets are enriched for a myriad of biological processes and stress responses, providing direct links to clock-controlled pathways and suggesting that CCA1 plays an important role in regulating a large subset of the rhythmic transcriptome. Although many of these target genes are evening expressed and contain the EE motif, a significant subset is morning phased and enriched for previously unrecognized motifs associated with CCA1 function. Furthermore, this work revealed several CCA1 targets that do not cycle in either LL or LD conditions. Together, our results emphasize an expanded role for the clock in regulating a diverse category of genes and key pathways in Arabidopsis and provide a comprehensive resource for future functional studies.

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