I. What Distinguishes a Pathogen from a Non-Pathogen?
II. Community Behavior of an Extracellular Pathogen
Part I: What Distinguishes a Pathogen from a Non-Pathogen?
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Isberg begins by asking what distinguishes a pathogen from a non-pathogen? Our bodies are host to many microbes, most of which do not cause disease and many of which are beneficial. Occasionally, however, microbes do cause infection and disease. Pathogens such as Staphlococcus, Vibrio cholera and Mycobacterium tuberculosis differ from normal non-pathogenic microbes in that they cause damage to the host. This damage allows the pathogen to colonize novel sites, antagonizes the host immune response, and facilitates spread of the pathogen. Isberg explains that pathogens inflict damage on their hosts by secreting toxins that act on host cell membranes or translocate across the cell membrane and usurp normal cellular functions. He also reviews the ways that host immune phagocytes defend against pathogens.
In his second talk, Isberg explains that pathogenic bacteria growing in tissues may form heterogeneous communities with bacteria expressing different protein profiles depending on their microenvironment. Using Yersinia pseudotuberculosis as a model system, Isberg and his colleagues studied gene expression patterns within bacterial colonies in the spleen. They found that expression of toxins and other virulence factors is influenced by cues such as proximity to host phagocytic cells or the concentration of secreted molecules such as NO. These results showed that only a subset of cells within a community of pathogenic bacteria need to express virulence factors.
Ralph Isberg is professor of molecular biology and microbiology at Tufts University School of Medicine and an Investigator of the Howard Hughes Medical Institute. Isberg’s lab strives to understand how pathogenic bacteria enter and grow within human cells, how they spread within the body and how they evade the immune system. The lab uses genetic and biochemical approaches to study these questions in the pathogenic bacteria Yersinia pseudotuberculosis and Legionella pneumophila.
Isberg received his AB in chemistry from Oberlin College and his PhD in microbiology and molecular genetics from Harvard University. He was a post-doctoral fellow at Stanford University with Stanley Falkow when he identified the first gene shown to be responsible for the entry of bacteria into host cells. Isberg’s contributions to microbiology have been recognized by election to the American Academy of Microbiology and the U.S National Academy of Sciences.
- Stanley Falkow iBioSeminar: Host-Pathogen Interaction and Human Disease
- Lora Hooper iBioSeminar: Mammalian Gut Microbiota
- John McKinney iBioSeminar: Tuberculosis a Persistent Threat to Global Health
- Pascale Cossart iBioSeminar: The Bacterial Pathogen Listeria Monocytogenes
- Grice EA, Segre JA. The human microbiome: our second genome. Annu Rev Genomics Hum Genet. 2012. 13:151-70. PMID: 22703178.
- Montoya M, Gouaux E. Beta-barrel membrane protein folding and structure viewed through the lens of alpha-hemolysin. Biochim Biophys Acta. 2003. 1609:19-27. PMID: 12507754.
- Robins WP, Mekalanos JJ. Genomic science in understanding cholera outbreaks and evolution of Vibrio cholerae as a human pathogen. Curr Top Microbiol Immunol. 2014. 379:211-29. PMID: 24590676.
- Fuchs TA, Abed U, Goosmann C, Hurwitz R, Schulze I, Wahn V, Weinrauch Y, Brinkmann V, Zychlinsky A. Novel cell death program leads to neutrophil extracellular traps. J Cell Biol. 2007. 176:231-41. PMID: 17210947.
- Barnes PD, Bergman MA, Mecsas J, Isberg RR. Yersinia pseudotuberculosis disseminates directly from a replicating bacterial pool in the intestine. J Exp Med. 2006. 203:1591-601. PMID: 16754724.
- Davis KM, Mohammadi S, Isberg RR. Community Behavior and Spatial Regulation within a Bacterial Microcolony in Deep Tissue Sites Serves to Protect against Host Attack. Cell Host Microbe. 2014. S1931-3128(14)00424-7. doi: 10.1016/j.chom.2014.11.008. PMID: 25500192.
- Pettersson J, Nordfelth R, Dubinina E, Bergman T, Gustafsson M, Magnusson KE, Wolf-Watz H. Modulation of virulence factor expression by pathogen target cell contact. Science. 1996. 273:1231-3. PMID: 8703058.
- Bliska JB, Wang X, Viboud GI, Brodsky IE. Modulation of innate immune responses by Yersinia type III secretion system translocators and effectors. Cell Microbiol. 2013. 15:1622-31. PMID: 23834311.
- Galán JE, Lara-Tejero M, Marlovits TC, Wagner S. Bacterial type III secretion systems: specialized nanomachines for protein delivery into target cells. Annu Rev Microbiol. 2014. 68:415-38. PMID: 25002086.
- Schraidt O, Marlovits TC. Three-dimensional model of Salmonella's needle complex at subnanometer resolution. Science. 2011. 331:1192-5. PMID: 21385715.