Organizing Committee Members - Infectious Diseases 2018
Kansas State University
Phillip E. Klebba.(Biography)
Phillip Klebba received his doctorate in Biochemistry at the University of California, Berkeley, working with the discoverer of siderophores, Dr. Joe . Neilands. He performed post-doctoral study with Drs. Leon Rosenberg at Stanford University and Hiroshi Nikaido at UC Berkeley, and was a visiting professor with Drs Maurice Hofnung, Institut Pasteur, Alain Charbit, Institut Necker, and Ron Kaback, UCLA. Dr. Klebba is Head of Biochemistry and Molecular Biophysics at Kansas State University. His research interests focus on biophysical approaches to problems in membrane transport, especially iron acquisition by bacteria.
Phillip E. Klebba.(Research Area)
My scientific interests focus on the mechanisms of iron acquisition proâ€ and eukaryotic cells, including transformed cells. This goal involved different processes in Gramâ€negative bacteria, Gramâ€positive bacteria, and most recently cancer cells. Iron is essential for cellular metabolism in both bacteria and animals, and consequently it is a virulence determinant in regard to bacterial pathogenesis. E. coli and its Gramâ€negative relatives (e.g., Salmonella, Shigella, Vibrio, Neisseria, Yersinia, Klebsiella, Pseudomonas, etc) secrete small molecules called siderophores (Gr; ironâ€bearer) that chelate iron in the environment. They then capture these ferric complexes with receptor proteins in their outer membrane (OM). Our findings defined the mechanism by which the E. coli OM protein FepA recognizes and transports the siderophore ferric enterobactin (FeEnt). Experiments with this system spanned many aspects of prokaryotic membrane biochemistry, including protein structure and function to produce selective permeability, the immunology and immunochemistry of bacterial cell surfaces, and the relationship of bacterial iron acquisition to infectious disease. We immunologically characterized FepA, used antibodies to predict its porinâ€like structure, showed that it contains a large channel through which iron enter the cell, and spectroscopically characterized the transport process. Our recent research was biophysical and more mechanistic, as we studied the transport actions of FepA and its accessory protein TonB, using electron spin resonance and fluorescence spectroscopic approaches. Our understanding of Gramâ€negative bacterial iron transport led to highâ€throughput screening methods to identify compounds in chemical libraries that block bacterial iron uptake, and thereby thwart pathogenesis. Our accomplishments include definition of the mechanism by which OM transporters accumulate iron against its concentration gradient, which requires energy and therefore falls into the category of active transport. They also require the actions of the additional cell envelope protein TonB, and are therefore â€œTonBâ€dependent.â€ Toward understanding this process I spent a year with Ron Kaback at UCLA studying the lactose permease, LacY. Our recent findings finally connected these two aspects of OM transport in a comprehensive mechanism. In the Rotational Surveillance and Energy Transfer (ROSET) model TonB undergoes energyâ€dependent motion (rotation) that transfers mechanical force to the OM. FepA uses this mechanical energy to undergo changes in structure that internalize FeEnt. By biophysical analyses in vivo we showed that internal motion in FepA controls transport through its pore, and TonBâ€derived energy transfer underlies structural rearrangements in FepA. The results portray OM iron transporters as highâ€affinity, dynamic receptors that actively capture iron and internalize it. After a sabbatical with Professor Alain Charbit at Institut Necker in Paris in 2002â€3, we expanded our research to consider the ability of the Gramâ€positive organism Listeria monocytogenes to acquire iron. We discovered heme and hemoglobin binding proteins in the listerial cell wall that are distinct from the iron transporters of Gramâ€negative cells, and explained their internalization of iron into the cytoplasm. Heme/ hemoglobin acquisition systems are crucial to the infectivity of Gramâ€positive bacteria, that besides L. monocytogenes include Staphylococcus, Streptococcus, Bacillus and more. These bacteria all use nearly identical systems to bind hemoglobin, extract its heme and then transport the iron porphyrin to support their growth in human and animal hosts. Our primary research aim is to use his biochemical knowledge of their mechanisms to generate therapeutic agents (i.e., antibiotics) or immunological reagents (monoclonal antibodies) that block heme acquisition and thereby combat Gramâ€positive bacterial pathogenesis.
Dutch Armed Forces / Royal Dutch Navy
Works internationally for several medical and biotech companies as scientific advisory board member and is also an active reserve-officer of the Royal Dutch Navy in his rank as Commander (OF4). For the Dutch Armed Forces he is CBRNe specialist with focus on (micro)biological and chemical threats and medical- and environmental functional specialist within the 1st CMI (Civil Military Interaction) Battalion of the Dutch Armed Forces. For Expertise France he is now managing an EU CBRN CoE public health project in West Africa. In his civilian position he is at this moment developing with MT-Derm in Berlin (Germany) a novel interdermal vaccination technology as well as a new therapy for cutaneous leishmaniasis for which he has won a Canadian â€˜Grand Challengeâ€™ grant. With Hemanua in Dublin (Ireland) he has developed an innovative blood separation unit, which is also suitable to produce convalescent plasma for Ebola Virus Disese therapy. He has finished both his studies in Medicine and in Biochemistry in The Netherlands with a doctorate and has extensive practical experience in cell biology, immuno-haematology, infectous diseaases, biodefense and transfusion medicine. His natural business acumen and negotiation competence helps to initiate new successful businesses, often generated from unexpected combinations of technologies.
Stef Stienstra(Research Area)
University of Lille,
Catherine MulliÃ© obtained a PhD in Microbiology and a PharmD at the University of Lille, France, in 1999. After a post-doc year at the FacultÃ© de Medicine in Amiens (Laboratoire dâ€™Immunologie, INSERM-EMI 0351), she was appointed as assistant professor at the FacultÃ© de Pharmacie in Amiens in 2000 and joined the LG-2A (Laboratoire de Glycochimie des Antimicrobiens et des Agroressources, UMR 7378 CNRS) in 2008. She has been a member of the French Society for Microbiology since 2000. Her research is focused on the development of new antimicrobial and antimalarial drugs, with a special interest in efflux-mediated antibiotic resistance in Pseudomonas aeruginosa and Acinetobacter baumannii. She currently heads the French part of a bilateral project funded by France and Algeria (Partenariat Hubert Curien Tassili) on this topic.
Catherine Mullie(Research Area)
development of new antimicrobial and antimalarial drugs, with a special interest in efflux-mediated antibiotic resistance in Pseudomonas aeruginosa and Acinetobacter baumannii