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Trends in Microbiology Aug 2020Colonization of the human stomach with Helicobacter pylori strains containing the cag pathogenicity island is a risk factor for development of gastric cancer. The cag... (Review)
Review
Colonization of the human stomach with Helicobacter pylori strains containing the cag pathogenicity island is a risk factor for development of gastric cancer. The cag pathogenicity island contains genes encoding a secreted effector protein (CagA) and components of a type IV secretion system (Cag T4SS). The molecular architecture of the H. pylori Cag T4SS is substantially more complex than that of prototype T4SSs in other bacterial species. In this review, we discuss recent discoveries pertaining to the structure and function of the Cag T4SS and its role in gastric cancer pathogenesis.
Topics: Animals; Antigens, Bacterial; Bacterial Proteins; Genomic Islands; Helicobacter Infections; Helicobacter pylori; Humans; Mice; Protein Conformation; Stomach; Stomach Neoplasms; Type IV Secretion Systems
PubMed: 32451226
DOI: 10.1016/j.tim.2020.02.004 -
Microbiology (Reading, England) May 2019The Type VI secretion system (T6SS) is a protein nanomachine that is widespread in Gram-negative bacteria and is used to translocate effector proteins directly into... (Review)
Review
The Type VI secretion system (T6SS) is a protein nanomachine that is widespread in Gram-negative bacteria and is used to translocate effector proteins directly into neighbouring cells. It represents a versatile bacterial weapon that can deliver effectors into distinct classes of target cells, playing key roles in inter-bacterial competition and bacterial interactions with eukaryotic cells. This versatility is underpinned by the ability of the T6SS to deliver a vast array of effector proteins, with many distinct activities and modes of interaction with the secretion machinery. Recent work has highlighted the importance and diversity of interactions mediated by T6SSs within polymicrobial communities, and offers new molecular insights into effector delivery and action in target cells.
Topics: Animals; Bacterial Proteins; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Type VI Secretion Systems
PubMed: 30893029
DOI: 10.1099/mic.0.000789 -
Nucleic Acids Research Jan 2020The Comprehensive Antibiotic Resistance Database (CARD; https://card.mcmaster.ca) is a curated resource providing reference DNA and protein sequences, detection models...
The Comprehensive Antibiotic Resistance Database (CARD; https://card.mcmaster.ca) is a curated resource providing reference DNA and protein sequences, detection models and bioinformatics tools on the molecular basis of bacterial antimicrobial resistance (AMR). CARD focuses on providing high-quality reference data and molecular sequences within a controlled vocabulary, the Antibiotic Resistance Ontology (ARO), designed by the CARD biocuration team to integrate with software development efforts for resistome analysis and prediction, such as CARD's Resistance Gene Identifier (RGI) software. Since 2017, CARD has expanded through extensive curation of reference sequences, revision of the ontological structure, curation of over 500 new AMR detection models, development of a new classification paradigm and expansion of analytical tools. Most notably, a new Resistomes & Variants module provides analysis and statistical summary of in silico predicted resistance variants from 82 pathogens and over 100 000 genomes. By adding these resistance variants to CARD, we are able to summarize predicted resistance using the information included in CARD, identify trends in AMR mobility and determine previously undescribed and novel resistance variants. Here, we describe updates and recent expansions to CARD and its biocuration process, including new resources for community biocuration of AMR molecular reference data.
Topics: Bacteria; Bacterial Proteins; Databases, Genetic; Drug Resistance, Bacterial; Genes, Bacterial; Software
PubMed: 31665441
DOI: 10.1093/nar/gkz935 -
FEMS Microbiology Reviews Jan 2020Protein aggregation occurs as a consequence of perturbations in protein homeostasis that can be triggered by environmental and cellular stresses. The accumulation of... (Review)
Review
Protein aggregation occurs as a consequence of perturbations in protein homeostasis that can be triggered by environmental and cellular stresses. The accumulation of protein aggregates has been associated with aging and other pathologies in eukaryotes, and in bacteria with changes in growth rate, stress resistance and virulence. Numerous past studies, mostly performed in Escherichia coli, have led to a detailed understanding of the functions of the bacterial protein quality control machinery in preventing and reversing protein aggregation. However, more recent research points toward unexpected diversity in how phylogenetically different bacteria utilize components of this machinery to cope with protein aggregation. Furthermore, how persistent protein aggregates localize and are passed on to progeny during cell division and how their presence impacts reproduction and the fitness of bacterial populations remains a controversial field of research. Finally, although protein aggregation is generally seen as a symptom of stress, recent work suggests that aggregation of specific proteins under certain conditions can regulate gene expression and cellular resource allocation. This review discusses recent advances in understanding the consequences of protein aggregation and how this process is dealt with in bacteria, with focus on highlighting the differences and similarities observed between phylogenetically different groups of bacteria.
Topics: Bacteria; Bacterial Proteins; Gene Expression Regulation, Bacterial; Phylogeny; Protein Aggregates; Protein Folding; Species Specificity
PubMed: 31633151
DOI: 10.1093/femsre/fuz026 -
Trends in Genetics : TIG Dec 2014Allosteric proteins have great potential in synthetic biology, but our limited understanding of the molecular underpinnings of allostery has hindered the development of... (Review)
Review
Allosteric proteins have great potential in synthetic biology, but our limited understanding of the molecular underpinnings of allostery has hindered the development of designer molecules, including transcription factors with new DNA-binding or ligand-binding specificities that respond appropriately to inducers. Such allosteric proteins could function as novel switches in complex circuits, metabolite sensors, or as orthogonal regulators for independent, inducible control of multiple genes. Advances in DNA synthesis and next-generation sequencing technologies have enabled the assessment of millions of mutants in a single experiment, providing new opportunities to study allostery. Using the classic LacI protein as an example, we describe a genetic selection system using a bidirectional reporter to capture mutants in both allosteric states, allowing the positions most crucial for allostery to be identified. This approach is not limited to bacterial transcription factors, and could reveal new mechanistic insights and facilitate engineering of other major classes of allosteric proteins such as nuclear receptors, two-component systems, G protein-coupled receptors, and protein kinases.
Topics: Allosteric Regulation; Bacterial Proteins; Binding Sites; DNA, Bacterial; Models, Molecular; Mutation; Nucleic Acid Conformation; Protein Binding; Protein Structure, Tertiary; Transcription Factors
PubMed: 25306102
DOI: 10.1016/j.tig.2014.09.004 -
Current Opinion in Structural Biology Aug 2021The bacterial outer membrane forms an impermeable barrier to the environment, but a wide variety of substances must cross it without compromising the membrane. Perhaps,... (Review)
Review
The bacterial outer membrane forms an impermeable barrier to the environment, but a wide variety of substances must cross it without compromising the membrane. Perhaps, the most fascinating transport phenomenon is the import and export of very large protein toxins using relatively small β-barrel proteins residing in the outer membrane. Progress has been made on three systems in recent years that shed light on this process. In this review, we summarize bacteriocin (toxin) import using TonB-dependent transporters and protein secretion by autotransporters and two partner secretion systems.
Topics: Bacterial Outer Membrane; Bacterial Outer Membrane Proteins; Bacterial Proteins; Biological Transport; Protein Transport
PubMed: 33901701
DOI: 10.1016/j.sbi.2021.03.007 -
Microbiology Spectrum Oct 2014Proteasomes are ATP-dependent, barrel-shaped proteases found in all three domains of life. In eukaryotes, proteins are typically targeted for degradation by... (Review)
Review
Proteasomes are ATP-dependent, barrel-shaped proteases found in all three domains of life. In eukaryotes, proteins are typically targeted for degradation by posttranslational modification with the small protein ubiquitin. In 2008, the first bacterial protein modifier, Pup (prokaryotic ubiquitin-like protein), was identified in Mycobacterium tuberculosis. Functionally analogous to ubiquitin, conjugation with Pup serves as a signal for degradation by the mycobacterial proteasome. Proteolysis-dependent and -independent functions of the M. tuberculosis proteasome are essential for virulence of this successful pathogen. In this article we describe the discovery of the proteasome as a key player in tuberculosis pathogenesis and the biology and biochemistry of the Pup-proteasome system.
Topics: Bacterial Proteins; Gene Expression Regulation, Bacterial; Mycobacterium tuberculosis; Proteasome Endopeptidase Complex; Protein Processing, Post-Translational; Proteolysis; Ubiquitins
PubMed: 26104367
DOI: 10.1128/microbiolspec.MGM2-0008-2013 -
International Journal of Molecular... Jul 2021The bacterial flagellum is a complex and dynamic nanomachine that propels bacteria through liquids. It consists of a basal body, a hook, and a long filament. The... (Review)
Review
The bacterial flagellum is a complex and dynamic nanomachine that propels bacteria through liquids. It consists of a basal body, a hook, and a long filament. The flagellar filament is composed of thousands of copies of the protein flagellin (FliC) arranged helically and ending with a filament cap composed of an oligomer of the protein FliD. The overall structure of the filament core is preserved across bacterial species, while the outer domains exhibit high variability, and in some cases are even completely absent. Flagellar assembly is a complex and energetically costly process triggered by environmental stimuli and, accordingly, highly regulated on transcriptional, translational and post-translational levels. Apart from its role in locomotion, the filament is critically important in several other aspects of bacterial survival, reproduction and pathogenicity, such as adhesion to surfaces, secretion of virulence factors and formation of biofilms. Additionally, due to its ability to provoke potent immune responses, flagellins have a role as adjuvants in vaccine development. In this review, we summarize the latest knowledge on the structure of flagellins, capping proteins and filaments, as well as their regulation and role during the colonization and infection of the host.
Topics: Bacteria; Bacterial Physiological Phenomena; Bacterial Proteins; Cytoskeleton; Flagella; Flagellin; Models, Molecular; Nanostructures
PubMed: 34299141
DOI: 10.3390/ijms22147521 -
Biomolecules Jun 2020Recently, a new class of prokaryotic compartments, collectively called encapsulins or protein nanocompartments, has been discovered. The shell proteins of these... (Review)
Review
Recently, a new class of prokaryotic compartments, collectively called encapsulins or protein nanocompartments, has been discovered. The shell proteins of these structures self-organize to form icosahedral compartments with a diameter of 25-42 nm, while one or more cargo proteins with various functions can be encapsulated in the nanocompartment. Non-native cargo proteins can be loaded into nanocompartments and the surface of the shells can be further functionalized, which allows for developing targeted drug delivery systems or using encapsulins as contrast agents for magnetic resonance imaging. Since the genes encoding encapsulins can be integrated into the cell genome, encapsulins are attractive for investigation in various scientific fields, including biomedicine and nanotechnology.
Topics: Bacterial Proteins; Models, Molecular; Nanocomposites; Protein Conformation
PubMed: 32604934
DOI: 10.3390/biom10060966 -
Open Biology Jun 2020Proper chromosome segregation during cell division is essential in all domains of life. In the majority of bacterial species, faithful chromosome segregation is mediated... (Review)
Review
Proper chromosome segregation during cell division is essential in all domains of life. In the majority of bacterial species, faithful chromosome segregation is mediated by the tripartite ParABS system, consisting of an ATPase protein ParA, a CTPase and DNA-binding protein ParB, and a centromere-like site. The site is most often located near the origin of replication and is segregated first after chromosome replication. ParB nucleates on before binding to adjacent non-specific DNA to form a multimeric nucleoprotein complex. ParA interacts with ParB to drive the higher-order ParB-DNA complex, and hence the replicating chromosomes, to each daughter cell. Here, we review the various models for the formation of the ParABS complex and describe its role in segregating the origin-proximal region of the chromosome. Additionally, we discuss outstanding questions and challenges in understanding bacterial chromosome segregation.
Topics: Bacteria; Bacterial Proteins; Chromosome Segregation; Chromosomes, Bacterial
PubMed: 32543349
DOI: 10.1098/rsob.200097