The aim of this proposal is to characterize a newly multivalent adhesion molecule (MAM7) found in the majority of Gram-negative pathogenic animal bacteria. We propose that MAM7 is involved in the initial contact of bacterial pathogens with host cells. As a representative for this type of molecule, we will use the MAM7 protein from Vibrio parahaemolyticus, an emerging pathogen that causes gastroenteritis through consumption of raw or undercooked seafood, to study the multivalent binding to host cells. We observe MAM7 dependent changes in the actin cytoskeleton in host cells. We predict that binding of MAM7 will trigger the production of more adhesion factors in the bacterial pathogens. Thus as one of our aims, we would like to uncover the signaling machinery activated in the bacteria and the host cell upon binding of MAM7. In another aim, we would like to understand the biochemical interaction of MAM7 with its two host cell receptors, fibronectin and phosphatidic acid. This information will be extremely valuable for future studies focused on MAM7 inhibitors. Finally, we observe that binding of non-pathogenic bacteria expressing MAM7 (BL21-MAM7) to host cells ameliorates cytotoxicity of Gram-negative pathogens expressing MAM7. We are interested in determining how broadly MAM7 provides a competitive advantage over other types of bacterial pathogens that do not express MAM7 but other types of adhesins. Together, these experiments will allow us to characterize the newly identified multivalent adhesion molecule MAM7 and will help to elucidate its value as a competitive inhibitor for a wide variety of bacterial pathogens.

Public Health Relevance

The aim of this proposal is to characterize a newly identified multivalent adhesion molecule (MAM7) that mediates the initial interaction between the eukaryotic host and the bacterial pathogen. We will use the MAM7 from Vibrio parahaemolyticus, an emerging pathogen that causes gastroenteritis through consumption of raw or undercooked sea food, to study the host/pathogen crosstalk upon binding of MAM7 to the previously identified host cell receptors, determine the biochemical interaction of host receptors with MAM7 and elucidate the value of MAM7 in augmenting bacterial infections.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1-IDM-A (80))
Program Officer
Hall, Robert H
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University of Texas Sw Medical Center Dallas
Schools of Medicine
United States
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Salomon, Dor; Orth, Kim (2013) What pathogens have taught us about posttranslational modifications. Cell Host Microbe 14:269-79
Hawley, Catherine Alice; Watson, Charlie Anne; Orth, Kim et al. (2013) A MAM7 peptide-based inhibitor of Staphylococcus aureus adhesion does not interfere with in vitro host cell function. PLoS One 8:e81216
Krachler, Anne Marie; Ham, Hyeilin; Orth, Kim (2012) Turnabout is fair play: use of the bacterial Multivalent Adhesion Molecule 7 as an antimicrobial agent. Virulence 3:68-71
Zhang, Lingling; Krachler, Anne Marie; Broberg, Christopher A et al. (2012) Type III effector VopC mediates invasion for Vibrio species. Cell Rep 1:453-60
Li, Yan; Al-Eryani, Rowaida; Yarbrough, Melanie L et al. (2011) Characterization of AMPylation on threonine, serine, and tyrosine using mass spectrometry. J Am Soc Mass Spectrom 22:752-61
Broberg, Christopher A; Calder, Thomas J; Orth, Kim (2011) Vibrio parahaemolyticus cell biology and pathogenicity determinants. Microbes Infect 13:992-1001
Broberg, Christopher A; Orth, Kim (2010) Tipping the balance by manipulating post-translational modifications. Curr Opin Microbiol 13:34-40