scholarly journals Xenogeneic modulation of the ClpCP protease of Bacillus subtilis by a phage-encoded adaptor-like protein

2019 ◽  
Vol 294 (46) ◽  
pp. 17501-17511 ◽  
Author(s):  
Nancy Mulvenna ◽  
Ingo Hantke ◽  
Lynn Burchell ◽  
Sophie Nicod ◽  
David Bell ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Gene Products ◽  
Bacterial Host ◽  
Systematic Analysis ◽  
Phage Gene ◽  
Cellular Processes ◽  
Bacteriophage Infection ◽  
Archaeal Viruses ◽  
Cytotoxic Proteins ◽  
Cellular Pathways

Like eukaryotic and archaeal viruses, which coopt the host's cellular pathways for their replication, bacteriophages have evolved strategies to alter the metabolism of their bacterial host. SPO1 bacteriophage infection of Bacillus subtilis results in comprehensive remodeling of cellular processes, leading to conversion of the bacterial cell into a factory for phage progeny production. A cluster of 26 genes in the SPO1 genome, called the host takeover module, encodes for potentially cytotoxic proteins that specifically shut down various processes in the bacterial host, including transcription, DNA synthesis, and cell division. However, the properties and bacterial targets of many genes of the SPO1 host takeover module remain elusive. Through a systematic analysis of gene products encoded by the SPO1 host takeover module, here we identified eight gene products that attenuated B. subtilis growth. Of the eight phage gene products that attenuated bacterial growth, a 25-kDa protein called Gp53 was shown to interact with the AAA+ chaperone protein ClpC of the ClpCP protease of B. subtilis. Our results further reveal that Gp53 is a phage-encoded adaptor-like protein that modulates the activity of the ClpCP protease to enable efficient SPO1 phage progeny development. In summary, our findings indicate that the bacterial ClpCP protease is the target of xenogeneic (dys)regulation by a SPO1 phage–derived factor and add Gp53 to the list of antibacterial products that target bacterial protein degradation and therefore may have utility for the development of novel antibacterial agents.

scholarly journals Xenogeneic regulation of the ClpCP protease ofBacillus subtilisby a phage-encoded adaptor-like protein

2019 ◽  
Author(s):  
Nancy Mulvenna ◽  
Ingo Hantke ◽  
Lynn Burchell ◽  
Sophie Nicod ◽  
Kürşad Turgay ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Bacterial Cell ◽  
Adaptor Protein ◽  
Gene Products ◽  
Progeny Production ◽  
Systematic Analysis ◽  
Physiological Processes ◽  
Small Proteins ◽  
Cytotoxic Proteins ◽  
Novel Strategy

AbstractSPO1 phage infection ofBacillus subtilisresults in a comprehensive remodelling of processes leading to conversion of the bacterial cell into a factory for phage progeny production. A cluster of 26 genes in the SPO1 genome, called the host takeover module, encodes for potentially cytotoxic proteins for the specific shut down of various host processes including transcription, DNA synthesis and cell division. However, the properties and bacterial targets of many genes of the SPO1 host takeover module remain elusive. Through a systematic analysis of gene products encoded by the SPO1 host takeover module we identified eight gene products which attenuatedB. subtilisgrowth. Out of the eight gene products that attenuated bacterial growth, a 25 kDa protein, called Gp53, was shown to interact with the AAA+ chaperone protein ClpC of the ClpCP protease ofB. subtilis. Results reveal that Gp53 functions like a phage encoded adaptor protein and thereby appears to alter the substrate specificity of the ClpCP protease to modulate the proteome of the infected cell to benefit efficient SPO1 phage progeny development. It seems that Gp53 represents a novel strategy used by phages to acquire their bacterial prey.Significance statementViruses of bacteria (phages) represent the most abundant living entities on the planet, and many aspects of our fundamental knowledge of phage–bacteria relationships remain elusive. Many phages encode specialised small proteins, which modulate essential physiological processes in bacteria in order to convert the bacterial cell into a ‘factory’ for phage progeny production – ultimately leading to the demise of the bacterial cell. We describe the identification of several antibacterial proteins produced by a prototypical phage that infectsBacillus subtilisand describe how one such protein subverts the protein control system of its host to benefit phage progeny development. The results have broad implications for our understanding of phage–bacteria relationships and the therapeutic application of phages and their gene products.

scholarly journals Cryptic prophage-encoded small protein DicB protects Escherichia coli from phage infection by inhibiting inner membrane receptor proteins

2019 ◽  
Author(s):  
Preethi T. Ragunathan ◽  
Carin K. Vanderpool
Keyword(s):  
Escherichia Coli ◽  
Cell Division ◽  
Functional Characterization ◽  
Phage Infection ◽  
Gene Products ◽  
Bacterial Host ◽  
Host Chromosome ◽  
Small Protein ◽  
Bacterial Physiology ◽  
Bacteriophage Infection

AbstractBacterial genomes harbor cryptic prophages that have lost genes required for induction, excision from host chromosomes, or production of phage progeny. Escherichia coli K12 strains contain a cryptic prophage Qin that encodes a small RNA, DicF, and small protein, DicB, that have been implicated in control of bacterial metabolism and cell division. Since DicB and DicF are encoded in the Qin immunity region, we tested whether these gene products could protect the E. coli host from bacteriophage infection. Transient expression of the dicBF operon yielded cells that were ~100-fold more resistant to infection by λ phage than control cells, and the phenotype was DicB-dependent. DicB specifically inhibited infection by λ and other phages that use ManYZ membrane proteins for cytoplasmic entry of phage DNA. In addition to blocking ManYZ-dependent phage infection, DicB also inhibited the canonical sugar transport activity of ManYZ. Previous studies demonstrated that DicB interacts with MinC, an FtsZ polymerization inhibitor, causing MinC localization to mid-cell and preventing Z ring formation and cell division. In strains producing mutant MinC proteins that do not interact with DicB, both DicB-dependent phenotypes involving ManYZ were lost. These results suggest that DicB is a pleiotropic regulator of bacterial physiology and cell division, and that these effects are mediated by a key molecular interaction with the cell division protein MinC.ImportanceTemperate bacteriophages can integrate their genomes into the bacterial host chromosome and exist as prophages whose gene products play key roles in bacterial fitness and interactions with eukaryotic host organisms. Most bacterial chromosomes contain “cryptic” prophages that have lost genes required for production of phage progeny but retain genes of unknown function that may be important for regulating bacterial host physiology. This study provides such an example – where a cryptic prophage-encoded product can perform multiple roles in the bacterial host and influence processes including metabolism, cell division, and susceptibility to phage infection. Further functional characterization of cryptic prophage-encoded functions will shed new light on host-phage interactions and their cellular physiological implications.

scholarly journals Molecular Signaling and Cellular Pathways for Virus Entry

ISRN Virology ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Pei-I Chi ◽  
Hung-Jen Liu
Keyword(s):  
Signaling Pathways ◽  
Viral Entry ◽  
Virus Entry ◽  
Host Cells ◽  
Target Cells ◽  
Molecular Signaling ◽  
Cellular Processes ◽  
Cellular Pathways ◽  
Host Life ◽  
Endocytic Vesicles

The cell signaling plays a pivotal role in regulating cellular processes and is often manipulated by viruses as they rely on the functions offered by cells for their propagation. The first stage of their host life is to pass the genetic materials into the cell. Although some viruses can directly penetrate into cytosol, in fact, most virus entry into their host cells is through endocytosis. This machinery initiates with cell type specific cellular signaling pathways, and the signaling compounds can be proteins, lipids, and carbohydrates. The activation can be triggered in a very short time after virus binds on target cells, such as receptors. The signaling pathways involved in regulation of viral entry are wide diversity that often cross-talk between different endocytosis results. Furthermore, some viruses have the ability to use the multiple internalization pathways which leads to the regulation being even more complex. In this paper, we discuss some recent advances in our understanding of cellular pathways for virus entry, molecular signaling during virus entry, formation of endocytic vesicles, and the traffic.

scholarly journals Toxoplasma gondii Development of Its Replicative Niche: in Its Host Cell and Beyond

2014 ◽  
Vol 13 (8) ◽  
pp. 965-976 ◽  
Author(s):  
Ira J. Blader ◽  
Anita A. Koshy
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cell ◽  
Host Cells ◽  
Content Type ◽  
Obligate Intracellular ◽  
Cellular Processes ◽  
High Prevalence ◽  
Life Threatening ◽  
Cell Processes ◽  
Cellular Pathways

ABSTRACTIntracellular pathogens can replicate efficiently only after they manipulate and modify their host cells to create an environment conducive to replication. While diverse cellular pathways are targeted by different pathogens, metabolism, membrane and cytoskeletal architecture formation, and cell death are the three primary cellular processes that are modified by infections.Toxoplasma gondiiis an obligate intracellular protozoan that infects ∼30% of the world's population and causes severe and life-threatening disease in developing fetuses, in immune-comprised patients, and in certain otherwise healthy individuals who are primarily found in South America. The high prevalence ofToxoplasmain humans is in large part a result of its ability to modulate these three host cell processes. Here, we highlight recent work defining the mechanisms by whichToxoplasmainteracts with these processes. In addition, we hypothesize why some processes are modified not only in the infected host cell but also in neighboring uninfected cells.

scholarly journals Regulation of cell cycle drivers by Cullin-RING ubiquitin ligases

2020 ◽  
Vol 52 (10) ◽  
pp. 1637-1651 ◽  
Author(s):  
Sang-Min Jang ◽  
Christophe E. Redon ◽  
Bhushan L. Thakur ◽  
Meriam K. Bahta ◽  
Mirit I. Aladjem
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Cell Cycle Progression ◽  
Ubiquitin Ligases ◽  
Anaphase Promoting Complex ◽  
Cycle Progression ◽  
Cellular Processes ◽  
Cellular Pathways ◽  
Regulation Of Cell Cycle ◽  
F Box Protein

Abstract The last decade has revealed new roles for Cullin-RING ubiquitin ligases (CRLs) in a myriad of cellular processes, including cell cycle progression. In addition to CRL1, also named SCF (SKP1-Cullin 1-F box protein), which has been known for decades as an important factor in the regulation of the cell cycle, it is now evident that all eight CRL family members are involved in the intricate cellular pathways driving cell cycle progression. In this review, we summarize the structure of CRLs and their functions in driving the cell cycle. We focus on how CRLs target key proteins for degradation or otherwise alter their functions to control the progression over the various cell cycle phases leading to cell division. We also summarize how CRLs and the anaphase-promoting complex/cyclosome (APC/C) ligase complex closely cooperate to govern efficient cell cycle progression.

Bacteriophage gene products as potential antimicrobials against tuberculosis

2019 ◽  
Vol 47 (3) ◽  
pp. 847-860 ◽  
Author(s):  
Maria Puiu ◽  
Christina Julius
Keyword(s):  
Phage Therapy ◽  
Basic Research ◽  
Gene Products ◽  
Cellular Processes ◽  
Tb Treatment ◽  
Current State ◽  
Rapid Spread ◽  
Long Time ◽  
State Of Research ◽  
Host Target

Abstract Tuberculosis (TB) is recognised as one of the most pressing global health threats among infectious diseases. Bacteriophages are adapted for killing of their host, and they were exploited in antibacterial therapy already before the discovery of antibiotics. Antibiotics as broadly active drugs overshadowed phage therapy for a long time. However, owing to the rapid spread of antibiotic resistance and the increasing complexity of treatment of drug-resistant TB, mycobacteriophages are being studied for their antimicrobial potential. Besides phage therapy, which is the administration of live phages to infected patients, the development of drugs of phage origin is gaining interest. This path of medical research might provide us with a new pool of previously undiscovered inhibition mechanisms and molecular interactions which are also of interest in basic research of cellular processes, such as transcription. The current state of research on mycobacteriophage-derived anti-TB treatment is reviewed in comparison with inhibitors from other phages, and with focus on transcription as the host target process.

scholarly journals Systematic analysis of Ca2+homeostasis inSaccharomyces cerevisiaebased on chemical-genetic interaction profiles

2017 ◽  
Vol 28 (23) ◽  
pp. 3415-3427 ◽  
Author(s):  
Farzan Ghanegolmohammadi ◽  
Mitsunori Yoshida ◽  
Shinsuke Ohnuki ◽  
Yuko Sukegawa ◽  
Hiroki Okada ◽  
...  
Keyword(s):  
Genetic Interaction ◽  
Principal Component ◽  
Analysis Of Covariance ◽  
High Dimensional ◽  
High Concentration ◽  
Systematic Analysis ◽  
Chemical Genetic ◽  
Cellular Processes ◽  
Cellular Compartments

We investigated the global landscape of Ca2+homeostasis in budding yeast based on high-dimensional chemical-genetic interaction profiles. The morphological responses of 62 Ca2+-sensitive (cls) mutants were quantitatively analyzed with the image processing program CalMorph after exposure to a high concentration of Ca2+. After a generalized linear model was applied, an analysis of covariance model was used to detect significant Ca2+–cls interactions. We found that high-dimensional, morphological Ca2+–cls interactions were mixed with positive (86%) and negative (14%) chemical-genetic interactions, whereas one-dimensional fitness Ca2+–cls interactions were all negative in principle. Clustering analysis with the interaction profiles revealed nine distinct gene groups, six of which were functionally associated. In addition, characterization of Ca2+–cls interactions revealed that morphology-based negative interactions are unique signatures of sensitized cellular processes and pathways. Principal component analysis was used to discriminate between suppression and enhancement of the Ca2+-sensitive phenotypes triggered by inactivation of calcineurin, a Ca2+-dependent phosphatase. Finally, similarity of the interaction profiles was used to reveal a connected network among the Ca2+homeostasis units acting in different cellular compartments. Our analyses of high-dimensional chemical-genetic interaction profiles provide novel insights into the intracellular network of yeast Ca2+homeostasis.

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