scholarly journals Molecular Mimicry: a Paradigm of Host-Microbe Coevolution Illustrated by Legionella

mBio ◽  
2020 ◽  
Vol 11 (5) ◽  
Author(s):  
Sonia Mondino ◽  
Silke Schmidt ◽  
Carmen Buchrieser
Keyword(s):  
Molecular Mimicry ◽  
Severe Pneumonia ◽  
Eukaryotic Cell ◽  
Host Cells ◽  
Exciting Field ◽  
Associated Bacteria ◽  
Host Interactions ◽  
Eukaryotic Proteins ◽  
Host Pathways

ABSTRACT Through coevolution with host cells, microorganisms have acquired mechanisms to avoid the detection by the host surveillance system and to use the cell’s supplies to establish themselves. Indeed, certain pathogens have evolved proteins that imitate specific eukaryotic cell proteins, allowing them to manipulate host pathways, a phenomenon termed molecular mimicry. Bacterial “eukaryotic-like proteins” are a remarkable example of molecular mimicry. They are defined as proteins that strongly resemble eukaryotic proteins or that carry domains that are predominantly present in eukaryotes and that are generally absent from prokaryotes. The widest diversity of eukaryotic-like proteins known to date can be found in members of the bacterial genus Legionella, some of which cause a severe pneumonia in humans. The characterization of a number of these proteins shed light on their importance during infection. The subsequent identification of eukaryotic-like genes in the genomes of other amoeba-associated bacteria and bacterial symbionts suggested that eukaryotic-like proteins are a common means of bacterial evasion and communication, shaped by the continuous interactions between bacteria and their protozoan hosts. In this review, we discuss the concept of molecular mimicry using Legionella as an example and show that eukaryotic-like proteins effectively manipulate host cell pathways. The study of the function and evolution of such proteins is an exciting field of research that is leading us toward a better understanding of the complex world of bacterium-host interactions. Ultimately, this knowledge will teach us how host pathways are manipulated and how infections may possibly be tackled.

scholarly journals Monoassociation with bacterial isolates reveals the role of colonization, community complexity and abundance on locomotor behavior in larval zebrafish

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Chelsea A. Weitekamp ◽  
Allison Kvasnicka ◽  
Scott P. Keely ◽  
Nichole E. Brinkman ◽  
Xia Meng Howey ◽  
...  
Keyword(s):  
Total Concentration ◽  
Bacterial Species ◽  
Locomotor Behavior ◽  
Host Cells ◽  
Individual Species ◽  
Zebrafish Model ◽  
Associated Bacteria ◽  
Larval Zebrafish ◽  
Toxicological Studies ◽  
Community Complexity

Abstract Background Across taxa, animals with depleted intestinal microbiomes show disrupted behavioral phenotypes. Axenic (i.e., microbe-free) mice, zebrafish, and fruit flies exhibit increased locomotor behavior, or hyperactivity. The mechanism through which bacteria interact with host cells to trigger normal neurobehavioral development in larval zebrafish is not well understood. Here, we monoassociated zebrafish with either one of six different zebrafish-associated bacteria, mixtures of these host-associates, or with an environmental bacterial isolate. Results As predicted, the axenic cohort was hyperactive. Monoassociation with three different host-associated bacterial species, as well as with the mixtures, resulted in control-like locomotor behavior. Monoassociation with one host-associate and the environmental isolate resulted in the hyperactive phenotype characteristic of axenic larvae, while monoassociation with two other host-associated bacteria partially blocked this phenotype. Furthermore, we found an inverse relationship between the total concentration of bacteria per larvae and locomotor behavior. Lastly, in the axenic and associated cohorts, but not in the larvae with complex communities, we detected unexpected bacteria, some of which may be present as facultative predators. Conclusions These data support a growing body of evidence that individual species of bacteria can have different effects on host behavior, potentially related to their success at intestinal colonization. Specific to the zebrafish model, our results suggest that differences in the composition of microbes in fish facilities could affect the results of behavioral assays within pharmacological and toxicological studies.

scholarly journals IKKε isoform switching governs the immune response against EV71 infection

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Ya-Ling Chang ◽  
Yu-Wen Liao ◽  
Min-Hsuan Chen ◽  
Sui-Yuan Chang ◽  
Yao-Ting Huang ◽  
...  
Keyword(s):  
Host Cells ◽  
Ev71 Infection ◽  
Virus Propagation ◽  
Host Interactions ◽  
Reciprocal Interactions ◽  
Isoform Switching ◽  
Gene Regulatory ◽  
Potential Strategy ◽  
Antiviral Innate Immunity ◽  
Interferon Responses

AbstractThe reciprocal interactions between pathogens and hosts are complicated and profound. A comprehensive understanding of these interactions is essential for developing effective therapies against infectious diseases. Interferon responses induced upon virus infection are critical for establishing host antiviral innate immunity. Here, we provide a molecular mechanism wherein isoform switching of the host IKKε gene, an interferon-associated molecule, leads to alterations in IFN production during EV71 infection. We found that IKKε isoform 2 (IKKε v2) is upregulated while IKKε v1 is downregulated in EV71 infection. IKKε v2 interacts with IRF7 and promotes IRF7 activation through phosphorylation and translocation of IRF7 in the presence of ubiquitin, by which the expression of IFNβ and ISGs is elicited and virus propagation is attenuated. We also identified that IKKε v2 is activated via K63-linked ubiquitination. Our results suggest that host cells induce IKKε isoform switching and result in IFN production against EV71 infection. This finding highlights a gene regulatory mechanism in pathogen-host interactions and provides a potential strategy for establishing host first-line defense against pathogens.

scholarly journals Characterization of symbiotic and associated bacteria from entomopathogenic nematode Heterorhabditis sp. (nematode: Heterorhabditidae) isolated from India

2020 ◽  
Vol 30 (1) ◽  
Author(s):  
Rashid Pervez ◽  
Showkat Ahmad Lone ◽  
Sasmita Pattnaik
Keyword(s):  
Insect Pests ◽  
Entomopathogenic Nematode ◽  
Alcaligenes Faecalis ◽  
Symbiotic Bacteria ◽  
Rrna Gene ◽  
Main Body ◽  
Associated Bacteria ◽  
Molecular Approaches

Abstract Background Entomopathogenic nematodes (EPNs) harboring symbiotic bacteria are one of the safest alternatives to the chemical insecticides for the control of various insect pests. Infective juveniles of EPNs locate a target insect, enter through the openings, and reach the hemocoel, where they release the symbiotic bacteria and the target gets killed by the virulence factors of the bacteria. Photorhabdus with Heterorhabditis spp. are well documented; little is known about the associated bacteria. Main body In this study, we explored the presence of symbiotic and associated bacteria from Heterorhabditis sp. (IISR-EPN 09) and characterized by phenotypic, biochemical, and molecular approaches. Six bacterial isolates, belonging to four different genera, were recovered and identified as follows: Photorhabdus luminescens, one each strain of Providencia vermicola, Pseudomonas entomophila, Alcaligenes aquatilis, and two strains of Alcaligenes faecalis based on the phenotypic, biochemical criteria and the sequencing of 16S rRNA gene. Conclusion P. luminescens is symbiotically associated with Heterorhabditis sp. (IISR-EPN 09), whereas P. vermicola, P. entomophila, A. aquatilis, and A. faecalis are the associated bacteria. Further studies are needed to determine the exact role of the bacterial associates with the Heterorhabditis sp.

scholarly journals Isolation and Characterization of Euglena gracilis-Associated Bacteria, Enterobacter sp. CA3 and Emticicia sp. CN5, Capable of Promoting the Growth and Paramylon Production of E. gracilis under Mixotrophic Cultivation

2021 ◽  
Vol 9 (7) ◽  
pp. 1496
Author(s):  
Rubiyatno ◽  
Kazuhiro Mori ◽  
Daisuke Inoue ◽  
Sunah Kim ◽  
Jaecheul Yu ◽  
...  
Keyword(s):  
Euglena Gracilis ◽  
Functional Foods ◽  
Mixotrophic Culture ◽  
Associated Bacteria ◽  
Isolation And Characterization ◽  
Growth Promoting ◽  
Value Functional ◽  
Mixotrophic Conditions ◽  
Microalgae Growth

Euglena gracilis produces paramylon, which is a feedstock for high-value functional foods and nutritional supplements. The enhancement of paramylon productivity is a critical challenge. Microalgae growth-promoting bacteria (MGPB) can improve microalgal productivity; however, the MGPB for E. gracilis remain unclear. This study isolated bacteria capable of enhancing E. gracilis growth and paramylon production under mixotrophic conditions. Enterobacter sp. CA3 and Emticicia sp. CN5 were isolated from E. gracilis grown with sewage-effluent bacteria under mixotrophic conditions at pH 4.5 or 7.5, respectively. In a 7-day E. gracilis mixotrophic culture with glucose, CA3 increased E. gracilis biomass and paramylon production 1.8-fold and 3.5-fold, respectively (at pH 4.5), or 1.9-fold and 3.5-fold, respectively (at pH 7.5). CN5 increased E. gracilis biomass and paramylon production 2.0-fold and 4.1-fold, respectively (at pH 7.5). However, the strains did not show such effects on E. gracilis under autotrophic conditions without glucose. The results suggest that CA3 and CN5 promoted both E. gracilis growth and paramylon production under mixotrophic conditions with glucose at pH 4.5 and 7.5 (CA3) or pH 7.5 (CN5). This study also provides an isolation method for E. gracilis MGPB that enables the construction of an effective E. gracilis–MGPB-association system for increasing the paramylon yield of E. gracilis.

scholarly journals Exploitation of conserved eukaryotic host cell farnesylation machinery by an F-box effector of Legionella pneumophila

2010 ◽  
Vol 207 (8) ◽  
pp. 1713-1726 ◽  
Author(s):  
Christopher T.D. Price ◽  
Tasneem Al-Quadan ◽  
Marina Santic ◽  
Snake C. Jones ◽  
Yousef Abu Kwaik
Keyword(s):  
Legionella Pneumophila ◽  
Biological Function ◽  
Host Cells ◽  
Dependent Manner ◽  
Protein Farnesyltransferase ◽  
Type Iv ◽  
Eukaryotic Proteins ◽  
Bacterial Effectors

Farnesylation involves covalent linkage of eukaryotic proteins to a lipid moiety to anchor them into membranes, which is essential for the biological function of Ras and other proteins. A large cadre of bacterial effectors is injected into host cells by intravacuolar pathogens through elaborate type III–VII translocation machineries, and many of these effectors are incorporated into the pathogen-containing vacuolar membrane by unknown mechanisms. The Dot/Icm type IV secretion system of Legionella pneumophila injects into host cells the F-box effector Ankyrin B (AnkB), which functions as platforms for the docking of polyubiquitinated proteins to the Legionella-containing vacuole (LCV) to enable intravacuolar proliferation in macrophages and amoeba. We show that farnesylation of AnkB is indispensable for its anchoring to the cytosolic face of the LCV membrane, for its biological function within macrophages and Dictyostelium discoideum, and for intrapulmonary proliferation in mice. Remarkably, the protein farnesyltransferase, RCE-1 (Ras-converting enzyme-1), and isoprenyl cysteine carboxyl methyltransferase host farnesylation enzymes are recruited to the LCV in a Dot/Icm-dependent manner and are essential for the biological function of AnkB. In conclusion, this study shows novel localized recruitment of the host farnesylation machinery and its anchoring of an F-box effector to the LCV membrane, and this is essential for biological function in vitro and in vivo.

scholarly journals Functional Characterization of a Redundant Plasmodium TRAP Family Invasin, TRAP-Like Protein, by Aldolase Binding and a Genetic Complementation Test

2008 ◽  
Vol 7 (6) ◽  
pp. 1062-1070 ◽  
Author(s):  
Kirsten Heiss ◽  
Hui Nie ◽  
Sumit Kumar ◽  
Thomas M. Daly ◽  
Lawrence W. Bergman ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Cell Entry ◽  
Host Cells ◽  
Complementation Test ◽  
Type I ◽  
Cycle Progression ◽  
Targeted Gene Disruption ◽  
Specific Host ◽  
Host Cell Entry

ABSTRACT Efficient and specific host cell entry is of exquisite importance for intracellular pathogens. Parasites of the phylum Apicomplexa are highly motile and actively enter host cells. These functions are mediated by type I transmembrane invasins of the TRAP family that link an extracellular recognition event to the parasite actin-myosin motor machinery. We systematically tested potential parasite invasins for binding to the actin bridging molecule aldolase and complementation of the vital cytoplasmic domain of the sporozoite invasin TRAP. We show that the ookinete invasin CTRP and a novel, structurally related protein, termed TRAP-like protein (TLP), are functional members of the TRAP family. Although TLP is expressed in invasive stages, targeted gene disruption revealed a nonvital role during life cycle progression. This is the first genetic analysis of TLP, encoding a redundant TRAP family invasin, in the malaria parasite.

scholarly journals Screening and Characterization of Sponge-Associated Bacteria Producing Bioactive Compounds Anti-Vibrio sp.

2018 ◽  
Vol 14 (3) ◽  
pp. 221-229 ◽  
Author(s):  
Aris Tri Wahyudi ◽  
Jepri Agung Priyanto ◽  
Wenang Maharsiwi ◽  
Rika Indri Astuti
Keyword(s):  
Bioactive Compounds ◽  
Associated Bacteria ◽  
Sponge Associated Bacteria

scholarly journals Characterization of Hepatitis C Virus Interaction with Heparan Sulfate Proteoglycans

2015 ◽  
Vol 89 (7) ◽  
pp. 3846-3858 ◽  
Author(s):  
Yan Xu ◽  
Pierre Martinez ◽  
Karin Séron ◽  
Guangxiang Luo ◽  
Fabrice Allain ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Apolipoprotein E ◽  
Heparan Sulfate ◽  
Heparan Sulfate Proteoglycans ◽  
Hcv Infection ◽  
Host Cells ◽  
Envelope Glycoproteins ◽  
Length Unit

ABSTRACTHepatitis C virus (HCV) entry involves binding to cell surface heparan sulfate (HS) structures. However, due to the lipoprotein-like structure of HCV, the exact contribution of virion components to this interaction remains controversial. Here, we investigated the relative contribution of HCV envelope proteins and apolipoprotein E in the HS-binding step. Deletion of hypervariable region 1, a region previously proposed to be involved in HS binding, did not alter HCV virion binding to HS, indicating that this region is not involved in this interaction in the context of a viral infection. Patient sera and monoclonal antibodies recognizing different regions of HCV envelope glycoproteins were also used in a pulldown assay with beads coated with heparin, a close HS structural homologue. Although isolated HCV envelope glycoproteins could interact with heparin, none of these antibodies was able to interfere with the virion-heparin interaction, strongly suggesting that at the virion surface, HCV envelope glycoproteins are not accessible for HS binding. In contrast, results from kinetic studies, heparin pulldown experiments, and inhibition experiments with anti-apolipoprotein E antibodies indicated that this apolipoprotein plays a major role in HCV-HS interaction. Finally, characterization of the HS structural determinants required for HCV infection by silencing of the enzymes involved in the HS biosynthesis pathway and by competition with modified heparin indicated thatN- and 6-O-sulfation but not 2-O-sulfation is required for HCV infection and that the minimum HS oligosaccharide length required for HCV infection is a decasaccharide. Together, these data indicate that HCV hijacks apolipoprotein E to initiate its interaction with specific HS structures.IMPORTANCEHepatitis C is a global health problem. Hepatitis C virus (HCV) infects approximately 130 million individuals worldwide, with the majority of cases remaining undiagnosed and untreated. In most infected individuals, the virus evades the immune system and establishes a chronic infection. As a consequence, hepatitis C is the leading cause of cirrhosis, end-stage liver disease, hepatocellular carcinoma, and liver transplantation. Virus infection is initiated by entry of the virus into the host cell. In this study, we provide new insights into the viral and cellular determinants involved in the first step of HCV entry, the binding of the virus to host cells. We show that apolipoprotein E is likely responsible for virus binding to heparan sulfate and thatN- and 6-O-sulfation of the heparan sulfate proteoglycans is required for HCV infection. In addition, the minimal HS length unit required for HCV infection is a decasaccharide.

scholarly journals N-Glycolyl GM1 Ganglioside as a Receptor for Simian Virus 40

2007 ◽  
Vol 81 (23) ◽  
pp. 12846-12858 ◽  
Author(s):  
Maria A. Campanero-Rhodes ◽  
Alicia Smith ◽  
Wengang Chai ◽  
Sandro Sonnino ◽  
Laura Mauri ◽  
...  
Keyword(s):  
Simian Virus 40 ◽  
High Specificity ◽  
Simian Virus ◽  
Receptor Expression ◽  
Host Cells ◽  
Gm1 Ganglioside ◽  
Ganglioside Gm1 ◽  
Virus Binding ◽  
Host Interactions ◽  
Sv40 Infection

ABSTRACT Carbohydrate microarrays have emerged as powerful tools in analyses of microbe-host interactions. Using a microarray with 190 sequence-defined oligosaccharides in the form of natural glycolipids and neoglycolipids representative of diverse mammalian glycans, we examined interactions of simian virus 40 (SV40) with potential carbohydrate receptors. While the results confirmed the high specificity of SV40 for the ganglioside GM1, they also revealed that N-glycolyl GM1 ganglioside [GM1(Gc)], which is characteristic of simian species and many other nonhuman mammals, is a better ligand than the N-acetyl analog [GM1(Ac)] found in mammals, including humans. After supplementing glycolipid-deficient GM95 cells with GM1(Ac) and GM1(Gc) gangliosides and the corresponding neoglycolipids with phosphatidylethanolamine lipid groups, it was found that GM1(Gc) analogs conferred better virus binding and infectivity. Moreover, we visualized the interaction of NeuGc with VP1 protein of SV40 by molecular modeling and identified a conformation for GM1(Gc) ganglioside in complex with the virus VP1 pentamer that is compatible with its presentation as a membrane receptor. Our results open the way not only to detailed studies of SV40 infection in relation to receptor expression in host cells but also to the monitoring of changes that may occur with time in receptor usage by the virus.

scholarly journals Characterization of a Replicating Mammalian Orthoreovirus with Tetracysteine-Tagged μNS for Live-Cell Visualization of Viral Factories

2017 ◽  
Vol 91 (22) ◽  
Author(s):  
Luke D. Bussiere ◽  
Promisree Choudhury ◽  
Bryan Bellaire ◽  
Cathy L. Miller
Keyword(s):  
Nonstructural Protein ◽  
Critical Role ◽  
Viral Proteins ◽  
Live Cell ◽  
Host Cells ◽  
Live Cells ◽  
Virus Protein ◽  
Mammalian Orthoreovirus ◽  
Virus Proteins

ABSTRACT Within infected host cells, mammalian orthoreovirus (MRV) forms viral factories (VFs), which are sites of viral transcription, translation, assembly, and replication. The MRV nonstructural protein μNS comprises the structural matrix of VFs and is involved in recruiting other viral proteins to VF structures. Previous attempts have been made to visualize VF dynamics in live cells, but due to current limitations in recovery of replicating reoviruses carrying large fluorescent protein tags, researchers have been unable to directly assess VF dynamics from virus-produced μNS. We set out to develop a method to overcome this obstacle by utilizing the 6-amino-acid (CCPGCC) tetracysteine (TC) tag and FlAsH-EDT2 reagent. The TC tag was introduced into eight sites throughout μNS, and the capacity of the TC-μNS fusion proteins to form virus factory-like (VFL) structures and colocalize with virus proteins was characterized. Insertion of the TC tag interfered with recombinant virus rescue in six of the eight mutants, likely as a result of loss of VF formation or important virus protein interactions. However, two recombinant (r)TC-μNS viruses were rescued and VF formation, colocalization with associating virus proteins, and characterization of virus replication were subsequently examined. Furthermore, the rTC-μNS viruses were utilized to infect cells and examine VF dynamics using live-cell microscopy. These experiments demonstrate active VF movement with fusion events as well as transient interactions between individual VFs and demonstrate the importance of microtubule stability for VF fusion during MRV infection. This work provides important groundwork for future in-depth studies of VF dynamics and host cell interactions. IMPORTANCE MRV has historically been used as a model to study the double-stranded RNA (dsRNA) Reoviridae family, the members of which infect and cause disease in humans, animals, and plants. During infection, MRV forms VFs that play a critical role in virus infection but remain to be fully characterized. To study VFs, researchers have focused on visualizing the nonstructural protein μNS, which forms the VF matrix. This work provides the first evidence of recovery of replicating reoviruses in which VFs can be labeled in live cells via introduction of a TC tag into the μNS open reading frame. Characterization of each recombinant reovirus sheds light on μNS interactions with viral proteins. Moreover, utilizing the TC-labeling FlAsH-EDT2 biarsenical reagent to visualize VFs, evidence is provided of dynamic VF movement and interactions at least partially dependent on intact microtubules.

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