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Virulence Dec 2021Bacterial proteases and peptidases are integral to cell physiology and stability, and their necessity in is no exception. Protein cleavage and processing mechanisms... (Review)
Review
Bacterial proteases and peptidases are integral to cell physiology and stability, and their necessity in is no exception. Protein cleavage and processing mechanisms within the bacterial cell serve to ensure that the cell lives and functions in its commensal habitat and can respond to new environments presenting stressful conditions. For , the human nasopharynx is its natural habitat. In the context of virulence, movement of to the lungs, blood, or other sites can instigate responses by the bacteria that result in their proteases serving dual roles of self-protein processors and virulence factors of host protein targets.
Topics: Animals; Bacterial Proteins; Genome, Bacterial; Humans; Immune Evasion; Lung; Mice; Nasopharynx; Peptide Hydrolases; Streptococcus pneumoniae; Virulence; Virulence Factors
PubMed: 33660565
DOI: 10.1080/21505594.2021.1889812 -
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 Spectrum Jul 2019The type VI secretion system (T6SS) is a multiprotein machine that uses a spring-like mechanism to inject effectors into target cells. The injection apparatus is... (Review)
Review
The type VI secretion system (T6SS) is a multiprotein machine that uses a spring-like mechanism to inject effectors into target cells. The injection apparatus is composed of a baseplate on which is built a contractile tail tube/sheath complex. The inner tube, topped by the spike complex, is propelled outside of the cell by the contraction of the sheath. The injection system is anchored to the cell envelope and oriented towards the cell exterior by a trans-envelope complex. Effectors delivered by the T6SS are loaded within the inner tube or on the spike complex and can target prokaryotic and/or eukaryotic cells. Here we summarize the structure, assembly, and mechanism of action of the T6SS. We also review the function of effectors and their mode of recruitment and delivery.
Topics: Bacteria; Bacterial Proteins; Cell Membrane; Protein Transport; Type VI Secretion Systems
PubMed: 31298206
DOI: 10.1128/microbiolspec.PSIB-0031-2019 -
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 -
Nature Jul 2022Bacterial conjugation is the fundamental process of unidirectional transfer of DNAs, often plasmid DNAs, from a donor cell to a recipient cell. It is the primary means...
Bacterial conjugation is the fundamental process of unidirectional transfer of DNAs, often plasmid DNAs, from a donor cell to a recipient cell. It is the primary means by which antibiotic resistance genes spread among bacterial populations. In Gram-negative bacteria, conjugation is mediated by a large transport apparatus-the conjugative type IV secretion system (T4SS)-produced by the donor cell and embedded in both its outer and inner membranes. The T4SS also elaborates a long extracellular filament-the conjugative pilus-that is essential for DNA transfer. Here we present a high-resolution cryo-electron microscopy (cryo-EM) structure of a 2.8 megadalton T4SS complex composed of 92 polypeptides representing 8 of the 10 essential T4SS components involved in pilus biogenesis. We added the two remaining components to the structural model using co-evolution analysis of protein interfaces, to enable the reconstitution of the entire system including the pilus. This structure describes the exceptionally large protein-protein interaction network required to assemble the many components that constitute a T4SS and provides insights on the unique mechanism by which they elaborate pili.
Topics: Bacterial Proteins; Conjugation, Genetic; Cryoelectron Microscopy; DNA; Evolution, Molecular; Fimbriae, Bacterial; Plasmids; Type IV Secretion Systems
PubMed: 35732732
DOI: 10.1038/s41586-022-04859-y -
Nucleic Acids Research Jan 2022The virulence factor database (VFDB, http://www.mgc.ac.cn/VFs/) is dedicated to presenting a comprehensive knowledge base and a versatile analysis platform for bacterial...
The virulence factor database (VFDB, http://www.mgc.ac.cn/VFs/) is dedicated to presenting a comprehensive knowledge base and a versatile analysis platform for bacterial virulence factors (VFs). Recent developments in sequencing technologies have led to increasing demands to analyze potential VFs within microbiome data that always consist of many different bacteria. Nevertheless, the current classification of VFs from various pathogens is based on different schemes, which create a chaotic situation and form a barrier for the easy application of the VFDB dataset for future panbacterial metagenomic analyses. Therefore, based on extensive literature mining, we recently proposed a general category of bacterial VFs in the database and reorganized the VFDB dataset accordingly. Thus, all known bacterial VFs from 32 genera of common bacterial pathogens collected in the VFDB are well grouped into 14 basal categories along with over 100 subcategories in a hierarchical architecture. The new coherent and well-defined VFDB dataset will be feasible and applicable for future panbacterial analysis in terms of virulence factors. In addition, we introduced a redesigned JavaScript-independent web interface for the VFDB website to make the database readily accessible to all users with various client settings worldwide.
Topics: Bacteria; Bacterial Proteins; Data Mining; Databases, Genetic; Gene Expression Regulation, Bacterial; Gene Regulatory Networks; Genome, Bacterial; Humans; Internet; Knowledge Bases; Molecular Sequence Annotation; Phylogeny; Protein Interaction Mapping; Software; Virulence Factors
PubMed: 34850947
DOI: 10.1093/nar/gkab1107 -
FEBS Letters Dec 2020Bacterial membrane proteins of the SbmA/BacA family are multi-solute transporters that mediate the uptake of structurally diverse hydrophilic molecules, including...
Bacterial membrane proteins of the SbmA/BacA family are multi-solute transporters that mediate the uptake of structurally diverse hydrophilic molecules, including aminoglycoside antibiotics and antimicrobial peptides. Some family members are full-length ATP-binding cassette (ABC) transporters, whereas other members are truncated homologues that lack the nucleotide-binding domains and thus mediate ATP-independent transport. A recent cryo-EM structure of the ABC transporter Rv1819c from Mycobacterium tuberculosis has shed light on the structural basis for multi-solute transport and has provided insight into the mechanism of transport. Here, we discuss how the protein architecture makes SbmA/BacA family transporters prone to inadvertent import of antibiotics and speculate on the question which physiological processes may benefit from multi-solute transport.
Topics: ATP-Binding Cassette Transporters; Anti-Bacterial Agents; Antigens, Bacterial; Bacterial Proteins; Biological Transport; Escherichia coli Proteins; Membrane Transport Proteins; Mycobacterium tuberculosis; Phosphoric Monoester Hydrolases; Substrate Specificity
PubMed: 32810294
DOI: 10.1002/1873-3468.13912 -
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 -
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