Elucidation of host–pathogen protein–protein interactions to uncover mechanisms of host cell rewiring

Abstract

Infectious diseases are the result of molecular cross-talks between hosts and their pathogens. These cross-talks are in part mediated by Host-Pathogen Protein-Protein Interactions (HP-PPI). HP-PPI play crucial roles in infections, as they may tilt the balance either in favor of the pathogens’ spread or their clearance. The identification of host proteins targeted by viral or bacterial pathogenic proteins necessary for the infection can provide insights into their underlying molecular mechanisms of pathogenicity, and potentially even single out pharmacological intervention targets. Here, we review the available methods to study HP-PPI, with a focus on recent mass spectrometry based methods to decipher bacterial – human infectious diseases and examine their relevance in uncovering host cell rewiring by pathogens.

Technological platforms used for the screening of new antiviral drugs

“…8 Thus, mapping the host-pathogen protein interactome may provide valuable insights into the biological functions of virulence factor proteins, highlight interactions critical to the pathogens' progression, and improve our overall understanding on the molecular basis of pathogenicity. 9 Recent advances in technology provide opportunities to overcome the limitations of traditional methodologies: any new analytical platform for this purpose must (a) facilitate incorporation of human an viral proteins in a single platform, (b) resolving the behavior of individual proteins in the viral life cycle, (c) identify altered signaling pathways, (d) identify therapeutic targets with quick, practical, affordable, and reliable assays. Microfluidic platforms, miniaturized devices with micrometer-sized channels and chambers, are good candidates for all of these requirements.…”

Microbial Proteomics and Their Importance in Medical Microbiology

“…Many proteomic techniques are used to study the host-pathogen interactions; it may lead to the discovery of important biological insights. Different kinds of methods available for 3.2 UNdERsTANdINg HOsT-PATHOgEN INTERACTIONs ANd INfECTIOUs dIsEAsEs detecting host-pathogen interactions, that is, yeast 2 hybrid, affinity purification-mass spectrometry, chemical cross-linking mass spectrometry, proximity-dependent labeling strategiesmass spectrometry, and protein microarray-based technologies and protein correlation profiling, have its own advantage and disadvantages (Table 3.1) (Nicod et al, 2017). Viral and bacterial proteins interact with host hub proteins or central proteins and alter the cellular processes.…”

Interactomics: Development of an efficient and improved Agrobacterium tumefaciens-mediated transformation method for transient expression of heterologous protein in recalcitrant plant tissues in planta

“…This knowledge is crucial to understand the biological mechanism of an infection and serves as a gateway for targeting novel treatments against pathogens [19]. In mammalian cells, AP-MS approach was used to identify host proteins that are targeted by infectious pathogens [19,20] such as in human-pathogenic bacteria interaction studies [21,22] and in human-virus interaction studies [7,23,24]. However, to date, AP-MS approach has yet to be adopted to study plant-pathogen interaction even in model plants presumably due to the hurdle in delivering parasitism genes into plant tissues, hence, the needs to design an optimised transformation procedure for successful isolation of pathogen-targeted plant proteins.…”