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Michael Apicella, MD

Professor Emeritus of Microbiology and Immunology

Email: michael-apicella@uiowa.edu

photo of Michael Apicella

Research Description

My long-range goal of my research has been to understand the factors involved human infections caused by the Gram-negative bacterial pathogens, Neisseria meningitidis, Neisseria gonorrhoeae,  nontypeable Haemophilus influenzae and Francisella tularenesis.   My research combines state of the art methodologies in molecular biology, cell biology, molecular biology and macromolecular chemistry to study mechanisms involved in these bacterial infections.  

In my early years, my laboratory has focused on the role that the major surface glycolipid, the lipooligosaccharide (LOS), the pathogenic Neisseria and Haemophilus played in the disease process caused by these organisms.  Our laboratory was the first to demonstrate that the carbohydrate portion of these molecules formed mimics of human glycosphingolipids which acted as a form of immune evasion by these microbes.  Using manipulation of the genes involved in biosynthesis of the toxic Lipid A portion of the LOS in these species, we were able to produce mutants in pathogenic Neisseria and Haemophilus whose LOS has substantially reduced toxicity (<10,000X) when compared to wild type strains.  This same approach has been used recently by Glaxo Smith Klein in their highly successful meningococcal serogroup B vaccine to reduce its toxicity.  We also were among the first to demonstrate that both the Neisseria and Haemophilus strains produce a biofilm and have elucidated the genes involved in its biosynthesis.  Our studies have shown that this biofilm is composed of bacterial DNA and these bacterial produce a nuclease which is involved in remodeling of the biofilm as it transitions from the sessile to the planktonic states.  We have done considerable amount of work in cellular microbiology, using primary human cells to identify the bacterial ligands responsible for entry of H. influenzae into airway epithelial cells and N. gonorrhoeae into cervical and male urethral cells. Recently, we have been focusing on developing potential vaccine antigens for prevention of N. gonorrhoeae using novel LOS structures we have find.