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A Comparative Approach to Characterize the Landscape of Host-Pathogen Protein-Protein Interactions
Published on: July 18, 2013
Pathogenicity and virulence: another view
1Long Island Jewish Medical Center, New Hyde Park, New York 11042.
Abstract:
The concepts of pathogenicity and virulence have governed our perception of microbial harmfulness since the time of Pasteur and Koch. These concepts resulted in the recognition and identification of numerous etiological agents and provided natural and synthetic agents effective in therapy and prevention of diseases. However, Koch's postulates--the premier product of this view--place the onus of harmfulness solely on the microbial world. Our recent experiences with polymicrobic and nosocomial infections, legionellosis, and acquired immunodeficiency syndrome point to the host as the major determinant of disease. The principles of parasitism, enunciated by Theobold Smith, approximate more accurately the disturbances of the host-parasite equilibrium we designate as infection. Many complex attributes of microbial anatomy and physiology have been obscured by our dependency on the pure-culture technique. For example, bacterial attachment organelles and the production of exopolysaccharides enable microorganisms to interact with mammalian glycocalyces and specific receptors. In addition, selection, through the use of therapeutic agents, aids in the progression of environmental organisms to members of the intimate human biosphere, with the potential to complicate the recovery of patients. These factors emphasize further the pivotal significance of host reactions in infections. Parasitism, in its negative aspects, explains the emergence of "new" infections that involve harm to more than host organs and cells: we may encounter subtler infections that reveal parasitic and host cell nucleic acid interactions in a form of genomic parasitism.
Insights
Microbial pathogenicity and virulence concepts overlook host factors in disease. Host reactions are crucial determinants in infections, including genomic parasitism, shifting focus from microbes to host-parasite equilibrium.
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- Traditional concepts of pathogenicity and virulence, rooted in Pasteur and Koch's work, focus on microbial agents causing disease.
- Koch's postulates attribute harmfulness solely to microbes, a view challenged by complex infections like polymicrobic, nosocomial, legionellosis, and acquired immunodeficiency syndrome.
Purpose of the Study:
- To re-evaluate the traditional understanding of microbial harmfulness by emphasizing the host's role in disease determination.
- To explore the host-parasite equilibrium, as proposed by Theobold Smith, as a more accurate model for understanding infections.
- To highlight the significance of host reactions and microbial-host interactions in the emergence of novel infectious diseases.
Main Methods:
- Review of historical concepts of pathogenicity and virulence.
- Analysis of recent clinical observations of complex infections (polymicrobic, nosocomial, legionellosis, AIDS).
- Consideration of microbial attributes (attachment organelles, exopolysaccharides) and their interaction with host cells.
- Examination of the impact of therapeutic agents on microbial adaptation and host colonization.
Main Results:
- Host factors are increasingly recognized as major determinants of disease severity and outcome.
- Microbial interactions with host cells, such as attachment to glycocalyces, are critical in infection dynamics.
- Therapeutic interventions can inadvertently promote the adaptation of environmental organisms to the human host.
- The concept of genomic parasitism, involving nucleic acid interactions between parasite and host, represents a subtler form of infection.
Conclusions:
- The host's immune response and intrinsic factors are pivotal in determining the outcome of infections.
- A shift from a purely microbe-centric view to a host-parasite equilibrium model is necessary for a comprehensive understanding of infectious diseases.
- Emerging infections may involve complex interactions at the genomic level, underscoring the dynamic interplay between host and pathogen.
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