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Periodic Report Summary 1 - PSMS-IN-INFLAMMATION (Imaging Innate Immunity of Staphylococcal Infections)

This study was designed to dissect the role of Staphylococcal phenol soluble modulins (PSMs) in bacterial pathogenesis and visualize how Staphylococcus aureus modulate host immunology in vivo. Surewaard has approached this research project by cutting-edge real-time in vivo imaging techniques but also use standard multidisciplinary methodologies: microbiology, histopathology, immunology and biochemistry.
Surewaard has learned and gained extensive experience in intravital microscopy to study bacterial pathogenesis in mice. He developed various fluorescent reporter strains in clinical important staphylococcal strains. The applicant gained experience in Immunohistochemistry to determine in which cellular compartment MRSA is replication and confirmed this data using electron microscopy. Using high resolution Z-stack images and newly developed replication reporter strains surewaard could show that S. aureus replicates and forms intracellular micro-colonies of up to 80 bacteria in Kupffer cells. In addition newly developed antibiotics could target this intracellular reservoir in Kupffer cells and this result is accepted for publication in JEM. In addition Surewaard and Z. Zeng have discovered the mechanism how Gram-positive bacteria a captured by Kupffer cells. Kupffer cells express Crig, however unlike previously thought this receptor does not recognize complement but it recognizes Lipoteichoic acid in the cell wall from gram positive bacteria. This result is accepted for publication in Cell Host and Microbes. In addition collaborations have been established with the pharmaceutical company Medimmune to address the mechanism of action of bi-specific antibodies that work against intracellular virulence factors that could result in new therapeutics for staphylococcal diseases.
The data generated by this study are currently accepted for publication high ranking biomedical research journals; Journal of Experimental Medicine and Cell Host and Microbes. By publishing in this data many scientist in the field of Infectious disease, immunology and microbiology will have access to it. Furthermore we identified a clinical problem that Methicillin-resistant Staphylococcus aureus (MRSA) actually thrives intracellularly. The pathogen survives and grows inside Kupffer cells and ultimately escapes to colonize other tissues. Based on these findings, a simple, inexpensive and rational way to target and eradicate the pathogen was further uncovered. This immunotherapeutic approach could help treat patients with MRSA bacteremia by increasing effectiveness of antibiotics and decreasing the length of administration.

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Life Sciences
Record Number: 187481 / Last updated on: 2016-08-19
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