scholarly journals Two SecA/SecY Systems with Distinct Roles in the Ecological Adaptations of Bacteria

2017 ◽  
Author(s):  
Xiaowei Jiang ◽  
Mario A. Fares
Keyword(s):  
Pathogenic Bacteria ◽  
Atp Hydrolysis ◽  
Functional Divergence ◽  
Evolutionary Divergence ◽  
Ecological Diversity ◽  
Secretion Systems ◽  
Membrane Pore ◽  
Functional Changes ◽  
Ecological Diversification ◽  
Ecological Adaptations

AbstractBacteria interact with their environment through the secretion of a specific set of proteins (known as secretome) through various secretion systems. Molecular modifications of these secretion systems may lead to the emergence of new bacterial-environment interactions, although this remains unexplored. In this study we investigate the possible link between molecular and functional changes in secretion proteins and the ecological diversity of bacteria. We studied functional modifications in secretion proteins by identifying events of functional evolutionary divergence—that is, changes at the molecular level that have driven changes of protein’s function. We present data supporting that these functional diversifications occurred in essential secretion proteins in bacteria. In particular, functional divergence of the two most important secretion proteins SecA and SecY in pathogenic bacteria suggests that molecular changes at these proteins are responsible for their adaptations to the host. Functional divergence has mainly occurred at protein domains involved in ATP hydrolysis in SecA and membrane pore formation in SecY. This divergence is stronger in pathogenic bacteria for protein copies resulting from the duplication of SecA/SecY, known as SecA2/SecY2. In concert with these results, we find that the secretome of bacteria with the strongest functional divergence is enriched for proteins specialized in the interaction with specific environments. We unravel evolutionary signatures that link mutations at secretion proteins to the ecological diversification of bacteria.

scholarly journals The many nuanced evolutionary consequences of duplicated genes

2018 ◽  
Author(s):  
Ashley I. Teufel ◽  
Mackenzie M. Johnson ◽  
Jon M. Laurent ◽  
Aashiq H. Kachroo ◽  
Edward M. Marcotte ◽  
...  
Keyword(s):  
Functional Divergence ◽  
Protein Structures ◽  
Evolutionary Divergence ◽  
Functional Changes ◽  
Binding Interface ◽  
Evolutionary Trajectories ◽  
Conventional Models ◽  
The Many ◽  
Evolutionary Consequences ◽  
Dosage Imbalance

AbstractGene duplication is seen as a major source of structural and functional divergence in genome evolution. Under the conventional models of sub- or neofunctionalizaton, functional changes arise in one of the duplicates after duplication. However, we suggest here that the presence of a duplicated gene can result in functional changes to its interacting partners. We explore this hypothesis by in-silico evolution of a heterodimer when one member of the interacting pair is duplicated. We examine how a range of selection pressures and protein structures leads to differential patterns of evolutionary divergence. We find that a surprising number of distinct evolutionary trajectories can be observed even in a simple three member system. Further, we observe that selection to correct dosage imbalance can affect the evolution of the initial function in several unexpected ways. For example, if a duplicate is under selective pressure to avoid binding its original binding partner, this can lead to changes in the binding interface of a non-duplicated interacting partner to exclude the duplicate. Hence, independent of the fate of the duplicate, its presence can impact how the original function operates. Additionally, we introduce a conceptual framework to describe how interacting partners cope with dosage imbalance after duplication. Contextualizing our results within this framework reveals that the evolutionary path taken by a duplicate’s interacting partners is highly stochastic in nature. Consequently, the fate of duplicate genes may not only be controlled by their own ability to accumulate mutations but also by how interacting partners cope with them.

scholarly journals The Many Nuanced Evolutionary Consequences of Duplicated Genes

2018 ◽  
Vol 36 (2) ◽  
pp. 304-314 ◽  
Author(s):  
Ashley I Teufel ◽  
Mackenzie M Johnson ◽  
Jon M Laurent ◽  
Aashiq H Kachroo ◽  
Edward M Marcotte ◽  
...  
Keyword(s):  
Functional Divergence ◽  
Protein Structures ◽  
Evolutionary Divergence ◽  
Functional Changes ◽  
Binding Interface ◽  
Evolutionary Trajectories ◽  
Conventional Models ◽  
The Many ◽  
Evolutionary Consequences ◽  
Dosage Imbalance

Abstract Gene duplication is seen as a major source of structural and functional divergence in genome evolution. Under the conventional models of sub or neofunctionalization, functional changes arise in one of the duplicates after duplication. However, we suggest here that the presence of a duplicated gene can result in functional changes to its interacting partners. We explore this hypothesis by in silico evolution of a heterodimer when one member of the interacting pair is duplicated. We examine how a range of selection pressures and protein structures leads to differential patterns of evolutionary divergence. We find that a surprising number of distinct evolutionary trajectories can be observed even in a simple three member system. Further, we observe that selection to correct dosage imbalance can affect the evolution of the initial function in several unexpected ways. For example, if a duplicate is under selective pressure to avoid binding its original binding partner, this can lead to changes in the binding interface of a nonduplicated interacting partner to exclude the duplicate. Hence, independent of the fate of the duplicate, its presence can impact how the original function operates. Additionally, we introduce a conceptual framework to describe how interacting partners cope with dosage imbalance after duplication. Contextualizing our results within this framework reveals that the evolutionary path taken by a duplicate’s interacting partners is highly stochastic in nature. Consequently, the fate of duplicate genes may not only be controlled by their own ability to accumulate mutations but also by how interacting partners cope with them.

scholarly journals Modulating Pathogenesis with Mobile-CRISPRi

2019 ◽  
Vol 201 (22) ◽  
Author(s):  
Jiuxin Qu ◽  
Neha K. Prasad ◽  
Michelle A. Yu ◽  
Shuyan Chen ◽  
Amy Lyden ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pathogenic Bacteria ◽  
Bacterial Species ◽  
Effector Proteins ◽  
Infection Model ◽  
Secretion Systems ◽  
Bacterial Genomes ◽  
Gene Encoding ◽  
Content Type ◽  
Animal Infection

ABSTRACT Conditionally essential (CE) genes are required by pathogenic bacteria to establish and maintain infections. CE genes encode virulence factors, such as secretion systems and effector proteins, as well as biosynthetic enzymes that produce metabolites not found in the host environment. Due to their outsized importance in pathogenesis, CE gene products are attractive targets for the next generation of antimicrobials. However, the precise manipulation of CE gene expression in the context of infection is technically challenging, limiting our ability to understand the roles of CE genes in pathogenesis and accordingly design effective inhibitors. We previously developed a suite of CRISPR interference-based gene knockdown tools that are transferred by conjugation and stably integrate into bacterial genomes that we call Mobile-CRISPRi. Here, we show the efficacy of Mobile-CRISPRi in controlling CE gene expression in an animal infection model. We optimize Mobile-CRISPRi in Pseudomonas aeruginosa for use in a murine model of pneumonia by tuning the expression of CRISPRi components to avoid nonspecific toxicity. As a proof of principle, we demonstrate that knock down of a CE gene encoding the type III secretion system (T3SS) activator ExsA blocks effector protein secretion in culture and attenuates virulence in mice. We anticipate that Mobile-CRISPRi will be a valuable tool to probe the function of CE genes across many bacterial species and pathogenesis models. IMPORTANCE Antibiotic resistance is a growing threat to global health. To optimize the use of our existing antibiotics and identify new targets for future inhibitors, understanding the fundamental drivers of bacterial growth in the context of the host immune response is paramount. Historically, these genetic drivers have been difficult to manipulate precisely, as they are requisite for pathogen survival. Here, we provide the first application of Mobile-CRISPRi to study conditionally essential virulence genes in mouse models of lung infection through partial gene perturbation. We envision the use of Mobile-CRISPRi in future pathogenesis models and antibiotic target discovery efforts.

scholarly journals Functional divergence of bitter taste receptors in a nectar-feeding bird

2019 ◽  
Vol 15 (9) ◽  
pp. 20190461 ◽  
Author(s):  
Yi Wang ◽  
Hengwu Jiao ◽  
Peihua Jiang ◽  
Huabin Zhao
Keyword(s):  
Secondary Metabolites ◽  
Bitter Taste ◽  
Functional Divergence ◽  
Taste Receptor ◽  
Bitter Taste Receptor ◽  
Functional Changes ◽  
Nectar Feeding ◽  
Gene Copies ◽  
Plant Pollinator ◽  
Higher Sensitivity

Nectar may contain many secondary metabolites that are commonly toxic and bitter-tasting. It has been hypothesized that such bitter-tasting secondary metabolites might keep the nectar exclusive to only a few pollinators. To test this hypothesis, we examined functional changes of bitter taste receptor genes ( Tas2r s) in a species of nectar-feeding bird (Anna's hummingbird) by comparing these genes with those from two closely related insect-feeding species (chimney swift and chuck-will's widow). We previously identified a larger number of Tas2r s in the hummingbird than in its close insectivorous relatives. In the present study, we demonstrate higher sensitivity and new functions in the hummingbird Tas2r gene copies generated by a lineage-specific duplication, which has been shaped by positive selection. These results suggest that the bitter taste may lead to increased sensitivities and specialized abilities of the hummingbird to detect bitter-tasting nectar. Moreover, this study potentially supports the hypothesis that bitter-tasting nectar may have been specialized for some pollinators, thus enforcing plant–pollinator mutualism.

scholarly journals Disruption of VirB6 Paralogs in Anaplasma phagocytophilum Attenuates Its Growth

2020 ◽  
Vol 202 (23) ◽  
Author(s):  
Francy L. Crosby ◽  
Ulrike G. Munderloh ◽  
Curtis M. Nelson ◽  
Michael J. Herron ◽  
Anna M. Lundgren ◽  
...  
Keyword(s):  
Anaplasma Phagocytophilum ◽  
Pathogenic Bacteria ◽  
Tandem Repeats ◽  
Model Systems ◽  
Accession Number ◽  
Secretion Systems ◽  
Altered Expression ◽  
Content Type ◽  
Obligate Intracellular

ABSTRACT Many pathogenic bacteria translocate virulence factors into their eukaryotic hosts by means of type IV secretion systems (T4SS) spanning the inner and outer membranes. Genes encoding components of these systems have been identified within the order Rickettsiales based upon their sequence similarities to other prototypical systems. Anaplasma phagocytophilum strains are obligate intracellular, tick-borne bacteria that are members of this order. The organization of these components at the genomic level was determined in several Anaplasma phagocytophilum strains, showing overall conservation, with the exceptions of the virB2 and virB6 genes. The virB6 loci are characterized by the presence of four virB6 copies (virB6-1 through virB6-4) arranged in tandem within a gene cluster known as the sodB-virB operon. Interestingly, the virB6-4 gene varies significantly in length among different strains due to extensive tandem repeats at the 3′ end. To gain an understanding of how these enigmatic virB6 genes function in A. phagocytophilum, we investigated their expression in infected human and tick cells. Our results show that these genes are expressed by A. phagocytophilum replicating in both cell types and that VirB6-3 and VirB6-4 proteins are surface exposed. Analysis of an A. phagocytophilum mutant carrying the Himar1 transposon within the virB6-4 gene demonstrated that the insertion not only disrupted its expression but also exerted a polar effect on the sodB-virB operon. Moreover, the altered expression of genes within this operon was associated with the attenuated in vitro growth of A. phagocytophilum in human and tick cells, indicating the importance of these genes in the physiology of this obligate intracellular bacterium in such different environments. IMPORTANCE Knowledge of the T4SS is derived from model systems, such as Agrobacterium tumefaciens. The structure of the T4SS in Rickettsiales differs from the classical arrangement. These differences include missing and duplicated components with structural alterations. Particularly, two sequenced virB6-4 genes encode unusual C-terminal structural extensions resulting in proteins of 4,322 (GenBank accession number AGR79286.1) and 9,935 (GenBank accession number ANC34101.1>) amino acids. To understand how the T4SS is used in A. phagocytophilum, we describe the expression of the virB6 paralogs and explore their role as the bacteria replicate within its host cell. Conclusions about the importance of these paralogs for colonization of human and tick cells are supported by the deficient phenotype of an A. phagocytophilum mutant isolated from a sequence-defined transposon insertion library.

scholarly journals Export von Gefahrgut: Helicobacter pylori und sein CagA-Protein

BIOspektrum ◽  
2020 ◽  
Vol 26 (6) ◽  
pp. 597-599
Author(s):  
Clara Lettl ◽  
Wolfgang Fischer
Keyword(s):  
Helicobacter Pylori ◽  
Pathogenic Bacteria ◽  
Type Iv Secretion ◽  
Host Cells ◽  
Bacterial Protein ◽  
Secretion Systems ◽  
Unusual Structure ◽  
Type Iv ◽  
Single Protein ◽  
Protein Transporters

Abstract Pathogenic bacteria often utilize type IV secretion systems to interact with host cells and to modify their microenvironment in a favourable way. The human pathogen Helicobacter pylori produces such a system to inject only a single protein, CagA, into gastric cells, but this injection represents a major risk factor for gastric cancer development. Here, we discuss the unusual structure of the Cag secretion nanomachine and other features that make it unique among bacterial protein transporters.

Type IV secretion machinery: molecular architecture and function

2013 ◽  
Vol 41 (1) ◽  
pp. 17-28 ◽  
Author(s):  
Vidya Chandran
Keyword(s):  
Virulence Factors ◽  
Legionella Pneumophila ◽  
Antibiotic Resistance Gene ◽  
Type Iv Secretion ◽  
Molecular Architecture ◽  
Paradigm Shifts ◽  
Secretion Systems ◽  
Membrane Pore ◽  
Type Iv ◽  
Monomeric Proteins

Bacteria have evolved several secretion machineries to bring about transport of various virulence factors, nutrients, nucleic acids and cell-surface appendages that are essential for their pathogenesis. T4S (Type IV secretion) systems are versatile secretion systems found in various Gram-negative and Gram-positive bacteria and in few archaea. They are large multisubunit translocons secreting a diverse array of substrates varying in size and nature from monomeric proteins to nucleoprotein complexes. T4S systems have evolved from conjugation machineries and are implicated in antibiotic resistance gene transfer and transport of virulence factors in Legionella pneumophila causing Legionnaires’ disease, Brucella suis causing brucellosis and Helicobacter pylori causing gastroduodenal diseases. The best-studied are the Agrobacterium tumefaciens VirB/D4 and the Escherichia coli plasmid pKM101 T4S systems. Recent structural advances revealing the cryo-EM (electron microscopy) structure of the core translocation assembly and high-resolution structure of the outer-membrane pore of T4S systems have made paradigm shifts in the understanding of T4S systems. The present paper reviews the advances made in biochemical and structural studies and summarizes our current understanding of the molecular architecture of this mega-assembly.

scholarly journals Elevated CO2 and nitrate levels increase wheat root-associated bacterial abundance and impact rhizosphere microbial community composition and function

2020 ◽  
Author(s):  
Alla Usyskin-Tonne ◽  
Yitzhak Hadar ◽  
Uri Yermiyahu ◽  
Dror Minz
Keyword(s):  
Bacterial Abundance ◽  
Root Exudation ◽  
Microbial Community Composition ◽  
Wheat Root ◽  
Root Surface ◽  
Structure And Function ◽  
Secretion Systems ◽  
Functional Changes ◽  
And Function ◽  
Mannose Metabolism

AbstractElevated CO2 stimulates plant growth and affects quantity and composition of root exudates, followed by response of its microbiome. Three scenarios representing nitrate fertilization regimes: limited (30 ppm), moderate (70 ppm) and excess nitrate (100 ppm) were compared under ambient and elevated CO2 (eCO2, 850 ppm) to elucidate their combined effects on root-surface-associated bacterial community abundance, structure and function. Wheat root-surface-associated microbiome structure and function, as well as soil and plant properties, were highly influenced by interactions between CO2 and nitrate levels. Relative abundance of total bacteria per plant increased at eCO2 under excess nitrate. Elevated CO2 significantly influenced the abundance of genes encoding enzymes, transporters and secretion systems. Proteobacteria, the largest taxonomic group in wheat roots (~ 75%), is the most influenced group by eCO2 under all nitrate levels. Rhizobiales, Burkholderiales and Pseudomonadales are responsible for most of these functional changes. A correlation was observed among the five gene-groups whose abundance was significantly changed (secretion systems, particularly type VI secretion system, biofilm formation, pyruvate, fructose and mannose metabolism). These changes in bacterial abundance and gene functions may be the result of alteration in root exudation at eCO2, leading to changes in bacteria colonization patterns and influencing their fitness and proliferation.

scholarly journals Evolution of regulatory signatures in primate cortical neurons at cell-type resolution

2020 ◽  
Vol 117 (45) ◽  
pp. 28422-28432
Author(s):  
Alexey Kozlenkov ◽  
Marit W. Vermunt ◽  
Pasha Apontes ◽  
Junhao Li ◽  
Ke Hao ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Brain Evolution ◽  
Cell Types ◽  
Regulatory Elements ◽  
Autism Spectrum ◽  
Projection Neurons ◽  
Evolutionary Divergence ◽  
Cell Type ◽  
Tissue Samples ◽  
Functional Changes

The human cerebral cortex contains many cell types that likely underwent independent functional changes during evolution. However, cell-type–specific regulatory landscapes in the cortex remain largely unexplored. Here we report epigenomic and transcriptomic analyses of the two main cortical neuronal subtypes, glutamatergic projection neurons and GABAergic interneurons, in human, chimpanzee, and rhesus macaque. Using genome-wide profiling of the H3K27ac histone modification, we identify neuron-subtype–specific regulatory elements that previously went undetected in bulk brain tissue samples. Human-specific regulatory changes are uncovered in multiple genes, including those associated with language, autism spectrum disorder, and drug addiction. We observe preferential evolutionary divergence in neuron subtype-specific regulatory elements and show that a substantial fraction of pan-neuronal regulatory elements undergoes subtype-specific evolutionary changes. This study sheds light on the interplay between regulatory evolution and cell-type–dependent gene-expression programs, and provides a resource for further exploration of human brain evolution and function.

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