Microbiology and Microbial Pathogenesis Program
Infectious Diseases and Immunity Branch
Division of Basic and Translational Sciences
We are seeking Concept Clearance for a Program Announcement (PA) that invites applications to develop and utilize innovative approaches to study the mechanisms by which two or more microorganisms contribute to the pathogenesis of infectious diseases. This announcement encourages investigators to think beyond the one organism-one disease concept, and instead, to consider the fact that many diseases are caused by the synergistic and inhibitory interactions of bacteria, viruses (with the exception of HIV), parasites, and fungi. Projects should include studies aimed at understanding the cellular and molecular interactions of pathogens with the normal (commensal) flora as well as the interactions among pathogens themselves, and how commensal organisms can be used to prevent or treat infections. In addition, the PA encourages research on the host responses to polymicrobial infections in order to develop new approaches to treat and prevent these infections. The development of co-infection models and the use of genomic and proteomic technologies to identify common virulence mechanisms and host response patterns, as well as the development of diagnostic and prognostic microbial/host signature patterns are encouraged. Because of the complexity of such projects, the establishment of collaborative scientific teams, both domestic and international, with diverse scientific disciplines studying polymicrobial diseases, including microbiology, immunology, biochemistry, clinical medicine, pathology, bioengineering, material science, imaging technology, and mathematical modeling are encouraged.
Examples of projects that would be responsive to this PA include, but are not limited to the following:
• Elucidation of the mechanisms by which viral or parasitic infections increase the risk for bacterial infection or vice versa;
• Determination of how, for example, surface adhesins are expressed or altered during microbial interactions;
• Identification of the mechanisms by which polymicrobial infections lead to enhanced resistance of microbes to acquired or innate immunity;
• Development of co-infection animal models or cell culture systems for multiple pathogens;
• Use of genomics and proteomics to identify microbial virulence genes that may be uniquely expressed during co-infection;
• Evaluation of host response patterns, in response to single vs. multiple infections (simultaneous or sequential activation), required to enhance or inhibit pathogenesis;
• Colonization and invasion of tissues by bacteria following recent viral infection; and,
• Development of biotherapeutics, such as phage therapy and probiotics, to block the pathogenicity of microorganisms.
To be responsive to this PA, the project must be restricted to polymicrobial interactions that have been well-documented to occur in clinical settings or are based on clinically significant studies, and are designed on the basis of sound scientific arguments with clearly defined endpoints such as immunological responses, production of toxins, membrane composition, metabolic activities or adherence to host cells. This initiative is not designed to support clinical trials; however the use of clinical samples from patients is allowed and encouraged.
The NIDCR expects to release this PA in collaboration with the NIAID and possibly other Institutes at the NIH.