-
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 -
The Journal of Biological Chemistry Apr 2014Microbial ester kinases identified in the past 3 decades came as a surprise, as protein phosphorylation on Ser, Thr, and Tyr amino acids was thought to be unique to... (Review)
Review
Microbial ester kinases identified in the past 3 decades came as a surprise, as protein phosphorylation on Ser, Thr, and Tyr amino acids was thought to be unique to eukaryotes. Current analysis of available microbial genomes reveals that "eukaryote-like" protein kinases are prevalent in prokaryotes and can converge in the same signaling pathway with the classical microbial "two-component" systems. Most microbial tyrosine kinases lack the "eukaryotic" Hanks domain signature and are designated tyrosine kinases based upon their biochemical activity. These include the tyrosine kinases termed bacterial tyrosine kinases (BY-kinases), which are responsible for the majority of known bacterial tyrosine phosphorylation events. Although termed generally as bacterial tyrosine kinases, BY-kinases can be considered as one family belonging to the superfamily of prokaryotic protein-tyrosine kinases in bacteria. Other members of this superfamily include atypical "odd" tyrosine kinases with diverse mechanisms of protein phosphorylation and the "eukaryote-like" Hanks-type tyrosine kinases. Here, we discuss the distribution, phylogeny, and function of the various prokaryotic protein-tyrosine kinases, focusing on the recently discovered Mycobacterium tuberculosis PtkA and its relationship with other members of this diverse family of proteins.
Topics: Bacterial Proteins; Mycobacterium tuberculosis; Phylogeny; Protein Structure, Tertiary; Protein-Tyrosine Kinases
PubMed: 24554699
DOI: 10.1074/jbc.R113.520015 -
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 -
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 -
The Journal of Biological Chemistry Mar 2013Protein glycosylation is widespread throughout all three domains of life. Bacterial protein N-glycosylation and its application to engineering recombinant glycoproteins... (Review)
Review
Protein glycosylation is widespread throughout all three domains of life. Bacterial protein N-glycosylation and its application to engineering recombinant glycoproteins continue to be actively studied. Here, we focus on advances made in the last 2 years, including the characterization of novel bacterial N-glycosylation pathways, examination of pathway enzymes and evolution, biological roles of protein modification in the native host, and exploitation of the N-glycosylation pathways to create novel vaccines and diagnostics.
Topics: Animals; Bacterial Infections; Bacterial Proteins; Glycoproteins; Glycosylation; Humans; Models, Immunological; Mutation; Periplasm; Signal Transduction
PubMed: 23329827
DOI: 10.1074/jbc.R112.417857 -
Science China. Life Sciences Jan 2016The study of human microbiota is an emerging research topic. The past efforts have mainly centered on studying the composition and genomic landscape of bacterial species... (Review)
Review
The study of human microbiota is an emerging research topic. The past efforts have mainly centered on studying the composition and genomic landscape of bacterial species within the targeted communities. The interaction between bacteria and hosts is the pivotal event in the initiation and progression of infectious diseases. There is a great need to identify and characterize the molecules that mediate the bacteria-host interaction. Bacterial surface exposed proteins play an important role in the bacteria- host interaction. Numerous surface proteins are glycosylated, and the glycosylation is crucial for their function in mediating the bacterial interaction with hosts. Here we present an overview of surface glycoproteins from bacteria that inhabit three major mucosal environments across human body: oral, gut and skin. We describe the important enzymes involved in the process of protein glycosylation, and discuss how the process impacts the bacteria-host interaction. Emerging molecular details underlying glycosylation of bacterial surface proteins may lead to new opportunities for designing anti-infective small molecules, and developing novel vaccines in order to treat or prevent bacterial infection.
Topics: Bacterial Proteins; Gastrointestinal Microbiome; Glycosylation; Host-Pathogen Interactions; Humans; Microbiota; Mouth Mucosa; Protein Processing, Post-Translational; Skin
PubMed: 26712033
DOI: 10.1007/s11427-015-4980-7 -
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 -
BMC Bioinformatics Mar 2017Protein-protein interactions (PPIs) can offer compelling evidence for protein function, especially when viewed in the context of proteome-wide interactomes. Bacteria...
BACKGROUND
Protein-protein interactions (PPIs) can offer compelling evidence for protein function, especially when viewed in the context of proteome-wide interactomes. Bacteria have been popular subjects of interactome studies: more than six different bacterial species have been the subjects of comprehensive interactome studies while several more have had substantial segments of their proteomes screened for interactions. The protein interactomes of several bacterial species have been completed, including several from prominent human pathogens. The availability of interactome data has brought challenges, as these large data sets are difficult to compare across species, limiting their usefulness for broad studies of microbial genetics and evolution.
RESULTS
In this study, we use more than 52,000 unique protein-protein interactions (PPIs) across 349 different bacterial species and strains to determine their conservation across data sets and taxonomic groups. When proteins are collapsed into orthologous groups (OGs) the resulting meta-interactome still includes more than 43,000 interactions, about 14,000 of which involve proteins of unknown function. While conserved interactions provide support for protein function in their respective species data, we found only 429 PPIs (~1% of the available data) conserved in two or more species, rendering any cross-species interactome comparison immediately useful. The meta-interactome serves as a model for predicting interactions, protein functions, and even full interactome sizes for species with limited to no experimentally observed PPI, including Bacillus subtilis and Salmonella enterica which are predicted to have up to 18,000 and 31,000 PPIs, respectively.
CONCLUSIONS
In the course of this work, we have assembled cross-species interactome comparisons that will allow interactomics researchers to anticipate the structures of yet-unexplored microbial interactomes and to focus on well-conserved yet uncharacterized interactors for further study. Such conserved interactions should provide evidence for important but yet-uncharacterized aspects of bacterial physiology and may provide targets for anti-microbial therapies.
Topics: Bacillus subtilis; Bacteria; Bacterial Proteins; Evolution, Molecular; Humans; Protein Interaction Mapping; Proteome; Salmonella enterica
PubMed: 28298180
DOI: 10.1186/s12859-017-1585-0 -
Cold Spring Harbor Perspectives in... Sep 2016Protein synthesis occurs on macromolecular machines, called ribosomes. Bacterial ribosomes and the translational machinery represent one of the major targets for... (Review)
Review
Protein synthesis occurs on macromolecular machines, called ribosomes. Bacterial ribosomes and the translational machinery represent one of the major targets for antibiotics in the cell. Therefore, structural and biochemical investigations into ribosome-targeting antibiotics provide not only insight into the mechanism of action and resistance of antibiotics, but also insight into the fundamental process of protein synthesis. This review summarizes the recent advances in our understanding of protein synthesis, particularly with respect to X-ray and cryoelectron microscopy (cryo-EM) structures of ribosome complexes, and highlights the different steps of translation that are targeted by the diverse array of known antibiotics. Such findings will be important for the ongoing development of novel and improved antimicrobial agents to combat the rapid emergence of multidrug resistant pathogenic bacteria.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Cryoelectron Microscopy; Protein Biosynthesis; Ribosomes
PubMed: 27481773
DOI: 10.1101/cshperspect.a025361