Proteome analysis of host-pathogen interactions: Investigation of pathogen responses to the host cell environment

PROTEOMICS ◽  
2011 ◽  
Vol 11 (15) ◽  
pp. 3203-3211 ◽  
Author(s):  
Frank Schmidt ◽  
Uwe Völker
Keyword(s):  
Host Cell ◽  
Proteome Analysis ◽  
Host Pathogen Interactions ◽  
Host Pathogen

scholarly journals Determinants of Phagosomal pH During Host-Pathogen Interactions

2021 ◽  
Vol 8 ◽  
Author(s):  
Johannes Westman ◽  
Sergio Grinstein
Keyword(s):  
Host Cell ◽  
Microbial Growth ◽  
Intracellular Pathogens ◽  
Ion Permeation ◽  
Host Pathogen Interactions ◽  
Counter Ion ◽  
Regulatory Machinery ◽  
Different Types ◽  
Host Pathogen ◽  
Luminal Ph

The ability of phagosomes to halt microbial growth is intimately linked to their ability to acidify their luminal pH. Establishment and maintenance of an acidic lumen requires precise co-ordination of H+ pumping and counter-ion permeation to offset the countervailing H+ leakage. Despite the best efforts of professional phagocytes, however, a number of specialized pathogens survive and even replicate inside phagosomes. In such instances, pathogens target the pH-regulatory machinery of the host cell in an effort to survive inside or escape from phagosomes. This review aims to describe how phagosomal pH is regulated during phagocytosis, why it varies in different types of professional phagocytes and the strategies developed by prototypical intracellular pathogens to manipulate phagosomal pH to survive, replicate, and eventually escape from the phagocyte.

scholarly journals Silica-coated phosphorescent nanoprobes for selective cell targeting and dynamic bioimaging of pathogen–host cell interactions

2020 ◽  
Vol 56 (51) ◽  
pp. 6989-6992 ◽  
Author(s):  
Federico Iovino ◽  
Padryk Merkl ◽  
Anastasia Spyrogianni ◽  
Birgitta Henriques-Normark ◽  
Georgios A. Sotiriou
Keyword(s):  
Host Cell ◽  
Dynamic Imaging ◽  
Cell Interactions ◽  
Cell Targeting ◽  
Host Pathogen Interactions ◽  
Host Pathogen ◽  
Host Cell Interactions

Optically stable nanophosphors coated with a nanothin amorphous SiO2 layer allow for dynamic imaging of cell host–pathogen interactions. The SiO2 layer facilitates the functionalization of the nanoprobes with antibodies for selective cell targeting.

scholarly journals Simultaneous transcriptional profiling of Leishmania major and its murine macrophage host cell reveals insights into host-pathogen interactions

BMC Genomics ◽  
2015 ◽  
Vol 16 (1) ◽  
Author(s):  
Laura A. L. Dillon ◽  
Rahul Suresh ◽  
Kwame Okrah ◽  
Hector Corrada Bravo ◽  
David M. Mosser ◽  
...  
Keyword(s):  
Host Cell ◽  
Leishmania Major ◽  
Transcriptional Profiling ◽  
Murine Macrophage ◽  
Host Pathogen Interactions ◽  
Host Pathogen

scholarly journals Lipids in host–pathogen interactions: Pathogens exploit the complexity of the host cell lipidome

2010 ◽  
Vol 49 (1) ◽  
pp. 1-26 ◽  
Author(s):  
Ynske P.M. van der Meer-Janssen ◽  
Josse van Galen ◽  
Joseph J. Batenburg ◽  
J. Bernd Helms
Keyword(s):  
Host Cell ◽  
Host Pathogen Interactions ◽  
Host Pathogen

scholarly journals Proteomic identification of Coxiella burnetii effector proteins targeted to the host cell mitochondria during infection

2020 ◽  
Author(s):  
Laura F. Fielden ◽  
Nichollas E. Scott ◽  
Catherine S. Palmer ◽  
Chen Ai Khoo ◽  
Hayley J Newton ◽  
...  
Keyword(s):  
Host Cell ◽  
Coxiella Burnetii ◽  
Q Fever ◽  
Bacterial Pathogens ◽  
Effector Proteins ◽  
Effector Protein ◽  
Subcellular Localisation ◽  
Host Pathogen Interactions ◽  
Affinity Enrichment ◽  
Host Pathogen

AbstractModulation of the host cell is integral to the survival and replication of microbial pathogens. Several intracellular bacterial pathogens deliver a cohort of bacterial proteins, termed ‘effector proteins’ into the host cell during infection by sophisticated protein translocation systems which manipulate cellular processes and functions. Despite the importance of these proteins during infection the functional contribution of individual effectors is poorly characterised, particularly in intracellular bacterial pathogens with large effector protein repertoires. Technical caveats have limited the capacity to study these proteins during a native infection, with many effector proteins having only been demonstrated to be translocated during over-expression of tagged versions. Here we present development of a novel strategy to examine effector proteins in the context of infection. We coupled a broad, unbiased proteomics-based screen with organelle purification to study the host-pathogen interactions occurring between the host cell mitochondrion and the Gram-negative, Q fever pathogen Coxiella burnetii. We identify 4 novel mitochondrially-targeted C. burnetii effector proteins, renamed Mitochondrial Coxiella effector protein (Mce) B to E. Examination of the subcellular localisation of ectopically expressed proteins in epithelial cells confirmed the mitochondrial localisation, demonstrating the robustness of our approach. Subsequent biochemical analysis and affinity enrichment proteomics of one of these effector proteins, MceC, revealed the protein is imported into mitochondria and can interact with components of the mitochondrial quality control machinery. Our study adapts high-sensitivity proteomics to the study of intracellular host-pathogen interactions occurring during infection, providing a robust strategy to examine the sub-cellular localisation of effector proteins during native infection. This approach could be applied to a range of pathogens and host cell compartments to provide a rich map of effector dynamics throughout infection.

scholarly journals The Ubiquitination System within Bacterial Host–Pathogen Interactions

2021 ◽  
Vol 9 (3) ◽  
pp. 638
Author(s):  
Vera Vozandychova ◽  
Pavla Stojkova ◽  
Kamil Hercik ◽  
Pavel Rehulka ◽  
Jiri Stulik
Keyword(s):  
Host Cell ◽  
Legionella Pneumophila ◽  
Pathogenic Bacteria ◽  
Vaccine Development ◽  
Shigella Flexneri ◽  
Effector Proteins ◽  
Deubiquitinating Enzymes ◽  
Host Pathogen Interactions ◽  
Host Pathogen ◽  
Ubiquitination System

Ubiquitination of proteins, like phosphorylation and acetylation, is an important regulatory aspect influencing numerous and various cell processes, such as immune response signaling and autophagy. The study of ubiquitination has become essential to learning about host–pathogen interactions, and a better understanding of the detailed mechanisms through which pathogens affect ubiquitination processes in host cell will contribute to vaccine development and effective treatment of diseases. Pathogenic bacteria (e.g., Salmonella enterica, Legionella pneumophila and Shigella flexneri) encode many effector proteins, such as deubiquitinating enzymes (DUBs), targeting the host ubiquitin machinery and thus disrupting pertinent ubiquitin-dependent anti-bacterial response. We focus here upon the host ubiquitination system as an integral unit, its interconnection with the regulation of inflammation and autophagy, and primarily while examining pathogens manipulating the host ubiquitination system. Many bacterial effector proteins have already been described as being translocated into the host cell, where they directly regulate host defense processes. Due to their importance in pathogenic bacteria progression within the host, they are regarded as virulence factors essential for bacterial evasion. However, in some cases (e.g., Francisella tularensis) the host ubiquitination system is influenced by bacterial infection, although the responsible bacterial effectors are still unknown.

scholarly journals Cellular metabolism in the defense against microbes

2021 ◽  
Vol 134 (5) ◽  
pp. jcs252023
Author(s):  
Lena Pernas
Keyword(s):  
Host Cell ◽  
Cell Metabolism ◽  
Critical Role ◽  
Cellular Metabolism ◽  
Human Metabolism ◽  
Host Pathogen Interactions ◽  
Nutrient Sources ◽  
Microbial Invasion ◽  
Host Pathogen ◽  
Host Metabolism

ABSTRACTThe study of metabolic changes associated with host–pathogen interactions have largely focused on the strategies that microbes use to subvert host metabolism to support their own proliferation. However, recent reports demonstrate that changes in host cell metabolism can also be detrimental to pathogens and restrict their growth. In this Review, I present a framework to consider how the host cell exploits the multifaceted roles of metabolites to defend against microbes. I also highlight how the rewiring of metabolic processes can strengthen cellular barriers to microbial invasion, regulate microbial virulence programs and factors, limit microbial access to nutrient sources and generate toxic environments for microbes. Collectively, the studies described here support a critical role for the rewiring of cellular metabolism in the defense against microbes. Further study of host–pathogen interactions from this framework has the potential to reveal novel aspects of host defense and metabolic control, and may inform how human metabolism impacts the progression of infectious disease.

scholarly journals Identification and Characterization of Sindbis Virus RNA-Host Protein Interactions

2018 ◽  
Vol 92 (7) ◽  
Author(s):  
Autumn T. LaPointe ◽  
Natasha N. Gebhart ◽  
Megan E. Meller ◽  
Richard W. Hardy ◽  
Kevin J. Sokoloski
Keyword(s):  
Host Cell ◽  
Growth Kinetics ◽  
Protein Interactions ◽  
Sindbis Virus ◽  
Life Cycles ◽  
Host Protein ◽  
Host Pathogen Interactions ◽  
Content Type ◽  
Interaction Sites ◽  
Host Pathogen

ABSTRACTArthropod-borne viruses, such as the members of the genusAlphavirus, are a significant concern to global public health. As obligate intracellular pathogens, RNA viruses must interact with the host cell machinery to establish and complete their life cycles. Despite considerable efforts to define the host-pathogen interactions essential for alphaviral replication, an unbiased and inclusive assessment of alphaviral RNA-protein interactions has not been undertaken. Moreover, the biological and molecular importance of these interactions, in the full context of their molecular function as RNA-binding proteins, has not been fully realized. The data presented here introduce a robust viral RNA-protein discovery method to elucidate the Sindbis virus (SINV) RNA-protein host interface. Cross-link-assisted mRNP purification (CLAMP) assessment revealed an extensive array of host-pathogen interactions centered on the viral RNAs (vRNAs). After prioritization of the host proteins associated with the vRNAs, we identified the site of protein-vRNA interaction by a UV cross-linking and immunoprecipitation sequencing (CLIP-seq) approach and assessed the consequences of the RNA-protein binding event of hnRNP K, hnRNP I, and hnRNP M in regard to viral infection. Here, we demonstrate that mutation of the prioritized hnRNP-vRNA interaction sites effectively disrupts hnRNP-vRNA interaction. Correlating with disrupted hnRNP-vRNA binding, SINV growth kinetics were reduced relative to wild-type parental viral infections in vertebrate and invertebrate tissue culture models of infection. The molecular mechanism leading to reduced viral growth kinetics was found to be dysregulated structural-gene expression. Collectively, this study further defines the scope and importance of the alphavirus host-pathogen vRNA-protein interactions.IMPORTANCEMembers of the genusAlphavirusare widely recognized for their potential to cause severe disease. Despite this recognition, there are no antiviral therapeutics, or safe and effective vaccines, currently available to treat alphaviral infection. Alphaviruses utilize the host cell machinery to efficiently establish and complete their life cycle. However, the extent and importance of host-pathogen RNA-protein interactions are woefully undercharacterized. The efforts detailed in this study fill this critical gap, and the significance of this research is 3-fold. First, the data presented here fundamentally expand the scope and understanding of alphavirus host-pathogen interactions. Second, this study identifies the sites of interaction for several prioritized interactions and defines the contribution of the RNA-protein interaction at the molecular level. Finally, these studies build a strategy by which the importance of the given host-pathogen interactions may be assessed in the future, using a mouse model of infection.

scholarly journals Proteomic identification of Coxiella burnetii effector proteins targeted to the host cell mitochondria during infection

2020 ◽  
pp. mcp.RA120.002370
Author(s):  
Laura F Fielden ◽  
Nichollas E. Scott ◽  
Catherine S Palmer ◽  
Chen Ai Khoo ◽  
Hayley J. Newton ◽  
...  
Keyword(s):  
Host Cell ◽  
Coxiella Burnetii ◽  
Q Fever ◽  
Bacterial Pathogens ◽  
Effector Proteins ◽  
Effector Protein ◽  
Subcellular Localisation ◽  
Host Pathogen Interactions ◽  
Affinity Enrichment ◽  
Host Pathogen

Modulation of the host cell is integral to the survival and replication of microbial pathogens. Several intracellular bacterial pathogens deliver bacterial proteins, termed ‘effector proteins’ into the host cell during infection by sophisticated protein translocation systems, which manipulate cellular processes and functions. The functional contribution of individual effectors is poorly characterised, particularly in intracellular bacterial pathogens with large effector protein repertoires. Technical caveats have limited the capacity to study these proteins during a native infection, with many effector proteins having only been demonstrated to be translocated during over-expression of tagged versions. Here we developed a novel strategy to examine effector proteins in the context of infection. We coupled a broad, unbiased proteomics-based screen with organelle purification to study the host-pathogen interactions occurring between the host cell mitochondrion and the Gram-negative, Q fever pathogen Coxiella burnetii. We identify 4 novel mitochondrially-targeted C. burnetii effector proteins, renamed Mitochondrial Coxiella effector protein (Mce) B to E. Examination of the subcellular localisation of ectopically expressed proteins confirmed their mitochondrial localisation, demonstrating the robustness of our approach. Subsequent biochemical analysis and affinity enrichment proteomics of one of these effector proteins, MceC, revealed the protein localises to the inner membrane and can interact with components of the mitochondrial quality control machinery. Our study adapts high-sensitivity proteomics to study intracellular host-pathogen interactions, providing a robust strategy to examine the sub-cellular localisation of effector proteins during native infection. This approach could be applied to a range of pathogens and host cell compartments to provide a rich map of effector dynamics throughout infection.

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