HID-HPP

Infectious diseases are disorders caused by (micro) organisms (viruses, bacteria, fungi and parasites). These have the potential to rapidly become global epidemics and pandemics, and are a leading cause of human disease and death worldwide, in particular in low income countries. Lower respiratory infections, HIV/AIDS and diarrheal diseases are ranked in the top ten causes of death globally, whereas malaria and tuberculosis are two of the major ten causes of death in low income countries. In developed countries infectious diseases are also important in immunosuppressed patients and transplant recipients. New diagnostic tests and therapeutic agents are required to reduce the mortality of these infectious diseases.

Date of Session: 6th October 2014
Name of Session: Infectious Diseases (HID)
Names of Session Chairs: Dr. Concha Gil (Universidad Complutense de Madrid, Spain) & Dr. Ileana M. Cristea (Princeton University, USA)

Names of Speakers/Presenters/Panellists:
Dr. Ileana Cristea, Princeton University USA
Dr. Concha Gil, Complutense University of Madrid, Madrid
Dr. Manuel Fuentes,Universidad of Salamanca, Spain
Dr. Sanjeeva Srivastava, IIT Bombay, India
Dr. Rafa Cantón, Hospital Universitario Ramón y Cajal, Spain
Dr. Jesús Fortún, Hospital Universitario Ramón y Cajal, Spain
Dr. Catherine Costello, Boston University, USA
Dr. Christopher Overall, University of British Columbia, Canada
Dr. Frank Schmidt, University of Greifswald, Germany
Dr. Joshua LaBaer, Arizona State University, USA
Dr. Peter Nilsson, KTH- Royal Institute of Technology, Sweden

Highlights and summary of session:
A. How to organize a community of scientists working in Infectious disease proteomics?
B. Potential scientific goals for this initiative

  • Selection of human proteins related to infectious diseases and immune system response based on published data using literature searches and bioinformatic analysis
  • Definition of human infectious disease-specific protein profiles (viruses, bacteria, fungi and parasites)
  • Selection of microbial proteins useful as diagnostic biomarkers.
  • Development of SRM methods for detection and quantification of human and microbial proteins
  • Generation of PeptideAtlas and SRMAtlas of selected microorganisms
  • Detection and quantification of these proteins by targeted proteomics in clinical samples
  • Detection and quantification of these proteins by affinity or antibodies based technologies
  • Identification of novel host factors for antiviral therapeutic intervention
  • Characterization of host-pathogen protein-protein interactions
  • Building of a web page to freely-access data
  • Collaboration with other HPP Initiatives (e. g. HAI – Antibodies, HPPP – Plasma Proteins, DBI- Disease Biomarkers Initiatives, iMOP- Initiative on Model Organism Proteomes

C. Contribution to J. Proteomics HUPO 2014 special issue
D. HID-HPP initiative Organization and future actions


B/D-HPP Sessions at HUPO 2015
Vancouver, Canada

Date of Session: 30th September 2015
Name of Session: Infectious Diseases (HID)-BD-HPP
Names of Session Chairs: Concha Gil, Universidad Complutense de Madrid, Spain & Ileana M. Cristea, Princeton University, USA
_____________
Names of Speakers/Presenters:
Sanjeeva Srivastava, IIT Bombay, India
Joshua LaBaer, TheBiodesignInstitute at Arizona State University, USA
Frank Schmidt, University Medicine Greifswald, Germany
Concha Gil, Universidad Complutense de Madrid, Spain
Manuel Fuentes, Cancer Research Center, Spain
Catherine Costello, Boston University School of Medicine, USA

Number of people attended: 30

Highlights and summary of session:
Highlights of each speaker and short over all summary of session (point form is sufficient, use back if necessary)

Proteomic characterization of host-pathogen interactions: lesson learned from Staphylococcus aureus 

To our knowledge the characterization of the proteome responses of microbial pathogens during infection is still limited due to the experimental challenges of the infection models. New and sophisticated analytical tools and methods are needed to overcome the limitations. In the presentation various experimental workflows already successfully applied in host-pathogen interaction experiments between S. aureus and various host cells were shown. The new tools such as iron nanoparticle labeling and classical enrichment strategies such FACS analysis in combination with SRM and DIA were discussed. The presented workflows enabled us to quantify nearly 50-60% of the predicted S. aureus proteins during infection.

 

Proteomic Analysis of Malaria Patients to Investigate Pathogenesis and Identify Surrogate Protein Markers

Proteomic analysis of Plasmodium falciparumand vivax induced alterations in humans from different endemic regions of India to decipher malaria pathogenesis and identify surrogate markers of severity.We have analyzed alterations in the human serum proteome as a consequence of non-severe and severe infections by the malaria parasite Plasmodium falciparumand vivax to identify markers related to disease severity and to obtain mechanistic insights about disease pathogenesis and host immune responses. Proteins showing altered serum abundance in falciparum malaria patients revealed the modulation of different physiological pathways.  Identified proteins including serum amyloid A, C-reactive protein, apolipoprotein E, haptoglobin, titin and nebulinwhich exhibited sequential alterations in their serum abundance in different severity levels of malaria, could serve as potential predictive markers for disease severity.

Protein arrays to study infectious diseases

The DNASU plasmid repository was established at the Biodesign Institute at Arizona State University as a nonprofit service core with the goal of providing sequence-verified, highly-annotated plasmids to researchers though an easy-to-use and accessible website (http://dnasu.org). There are gene collections of Human, Saccharomyces cerevisiae, Vibrio cholera, Pseudomonas aeruginosa, Francisellatulariensis, viruses etc. These collections can be used to develop nucleic acid programmable protein arrays, where thousands of protein features are directly expressed by nucleic acids on the array surface. These arrays can be used to analyze sera from patients and controls.  We have carried out a study of all 262 outer membrane and exported P. aeruginosa proteins by a NAPPA array and it was possible to identify 12 proteins that trigger an adaptive immune response in cystic fibrosis and acutely infected patients, providing valuable information about which bacterial proteins are actually recognized by the immune system in vivo during the natural course of infection.In another study we evaluated the association between viral infections and T1D by profiling anti-viral antibodies using a high-throughput immunoproteomics approach in new-onset T1D patients. A viral protein array comprising the complete proteomes of seven viruses associated with T1D and open reading frames (ORFs) from other common viruses was constructed. Antibody responses to Epstein-Barr virus (EBV) were significantly higher in cases than controls, whereas the other viruses showed no differences suggesting a potential role for EBV in T1D development.

Fungal Proteomics to study infectious diseases.The model of invasive candidiasis.

We are using different approaches to study host-pathogen interactions. Genomics, proteomics and bioinformatics analysis, using the in vitro model “Candida albicans– macrophages”, allowed us to discover that fungi inside macrophages are dying by apoptosis.  A targeted proteomic approach of proteins involved in apoptosis is underway. A deep knowledge of C. albicans apoptosis would be very important for the development of new treatments for invasive candidiasis. A Candida albicansPeptideAtlas, a valuable resource for the selection of candidate proteotypic peptides for targeted proteomics experiments, was developed.

At the same time we are analyzing the signaling pathways in macrophages that are involved in the recognition and the destruction of the fungi using quantitative proteomics of ATP binding proteins and targeted proteomics of kinases involved in the immune response. 

Finally, different diagnosis and prognosis strategies based on antibody detection, fungal or human protein detection in sera from patients with invasive candidiasiswere discussed including different examples of biomarker discovery and validation.

Round table discussion:

A round table,moderated by Catherine Costello and Manuel Fuentes, took place. The following points were discussed:

(1)How can scientists working in Infectious disease proteomics collaborate?

(2)Development of SRM methods for detection and quantification of human and microbial proteins

(3) Detection and quantification of these proteins by affinity or antibodies based technologies

(4) Building of a web page to freely-access data

(5)Dissemination of HID-HPP activities (reports, special issues)

A web page of this initiative will be created and two special issues in “Molecular and Cellular Proteomics” and in “Translational Proteomics” devoted to Infectious diseases were announced.