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What I Do

What I Do. Mike Bachman MD PhD Assistant Professor Director, Molecular Microbiology. Duties. Clinical Director of Molecular Microbiology M Labs Service Line Director Molecular Microbiology Malaria Diagnosis Research Principal Investigator Innate Immunity to Bacterial Infections

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What I Do

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  1. What I Do Mike Bachman MD PhD Assistant Professor Director, Molecular Microbiology

  2. Duties • Clinical • Director of Molecular Microbiology • M Labs Service Line Director • Molecular Microbiology • Malaria Diagnosis • Research • Principal Investigator • Innate Immunity to Bacterial Infections • Member, Distributed Health Technologies Cluster

  3. Molecular Microbiology Lab • Section of Clinical Microbiology Laboratory • Testing Performed Seven Days a Week • Dedicated Team of Technologists • Coverage of Day Shift • Afternoon coverage soon

  4. Molecular Microbiology Test Menu • Diagnostic Testing • Herpes Simplex Virus (CSF) • Detection and Typing • Chlamydia trachomatis/ Neisseria gonnorhoeae • Bordetellapertussis/parapertussis • Clostridium difficileToxin B • Pneumocystis jiroveci • Respiratory Viruses • Influenza A • Influenza B • Respiratory Syncitial Virus (RSV) • Parainfluenza 1,2,3 • Human Metapneumovirus

  5. Molecular Microbiology Test Menu • Viral Load Monitoring • HIV • Hepatitis B • Hepatitis C • CMV • Viral Genotyping • Hepatitis C • Adjunct Testing • High-Risk Human Papillomavirus

  6. Test Development • Herpes Lesion Diagnosis • High throughput testing to replace culture • Platform for Quantitative Testing • Abbott m2000 (HIV, HBV, HCV) • EBV • Platform for Qualitative Testing • HSV, Bordetellapertussis/parapertussis, C. difficile • Basis for expanding testing • Human Papillomavirus • 4 FDA-approved assays • Potential for HPV 16/18 Genotyping

  7. Duties • Clinical • Director of Molecular Microbiology • M Labs Service Line Director • Molecular Microbiology • Malaria Diagnosis • Research • Principal Investigator • Innate Immunity to Bacterial Infections • Member, Distributed Health Technologies Cluster

  8. Asymptomatic intestinal colonization - 75% of patients Nasopharynx Colonization -19% of patients Pneumonia #3 hospital-acquired cause Bacteremia Urinary tract infection Klebsiella pneumoniae • Genetically tractable • Iron-chelating Siderophores are major virulence factors RICHARDS, M.J. ET AL (1999) PEDIATRICS. 103:E39; ZAOUTIS, T.E. ET AL (2005) PEDIATRICS. 115: 942; LAWLOR, M.S. ET. AL, (2007) INFECT IMMUN. 75:1463; NASSIF, X. AND SANSONETTI, P.J. (1986) INFECT IMMUN. 54:603

  9. Innate Immune Response to Microbial Iron Metabolism • Iron is required by both bacterial pathogens and human hosts • Gram-negative pathogens acquire iron by secreting iron chelators called siderophores • Enterobactin • Lipocalin 2 is an innate immune protein that binds Enterobactin to inhibit bacterial growth Lipocalin 2 Enterobactin

  10. Glycosylated Enterobactin • Glucose on catechol rings prevents Lcn2 binding • Yersiniabactin Fischbach, M.A. et. al. 2006. PNAS USA, 103:16502 K. Pneumoniae May produce Siderophores to evade Lipocalin 2 Does K. pneumoniae require these siderophores to cause disease?

  11. Yersiniabactin is prevalent among K. pneumoniae respiratory isolates

  12. The interaction between siderophores and lipocalin 2 determines the pattern of pneumonia Bachman, M.A., Lenio, S., Schmidt, L. et al 2012 Submitted.

  13. + LCN2 Lipocalin 2 bound to enterobactin triggers inflammation NELSON ET AL. INFECTION AND IMMUNITY 2007

  14. Ent-Lcn2 may alter gene expression via hypoxia-response pathways • HIF-1α • INDUCED BY HYPOXIA OR IRON CHELATION • REGULATES: • MYELOID CELL FUNCTION • PRO-INFLAMMATORY CYTOKINE SIGNALING (TNF) • CELL SURVIVAL/APOPTOSIS • ANGIOGENESIS (VEGFA) R. KUICK, S. LENIO, V. HOLDEN CRAMER ET AL. 2003 CELL; PEYSSONNAUX ET. AL 2007 J IMMUNOL; WALMSLEY ET. AL 2011 JCI

  15. Acknowledgements • Pathology/ U of M • Jeff Warren • Jay Hess • Lindsay Schmidt • RorkKuick • Harry Mobley • Clinical Micro Lab • Duane Newton • Rosemary Hankerd • The Molecular Team • Bachman Lab • Steve Lenio • Victoria Holden • NIH/NIGMS • K08 Career Development Award

  16. Test Methodology • Real-Time PCR • Closed System (low cross-contamination risk) • Simultaneous Amplification and Detection of RNA or DNA • Quantitative or Qualitative

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