Michael A. Apicella, M.D.
M.D., SUNY Downstate Medical Center, 1963 |
Professor of Microbiology Campus address: 3-370 BSB Mailing address: 51 Newton Rd. 3-370 Bowen Science Building Iowa City, IA 52242 Phone: 319-335-7807 Email: |
Pathogenesis of Human Infection by Pathogenic Neisseria and Haemophilus
Research Program: The long range goal of Dr. Apicella's research is to understand the factors involved in the pathogenesis of human pathogenic Neisseria and nontypeable Haemophilus influenzae infections in order to develop methods to inhibit these infectious processes either by vaccination or chemotherapy. These organisms are strict human pathogens and cause considerable disease worldwide. Dr. Apicella's research combines state of the art methodologies in molecular biology, cell biology, bioinformatics and macromolecular chemistry to study mechanisms involved in bacterial pathogenesis.
The studies of the Apicella laboratory on Neisseria gonorrhoeae have shown that this organism is unique since it utilizes different mechanisms of infection in men and in women. In men, the organism is able to infect the urethral epithelial cell by the binding of the terminal lactosamine on the gonococcal lipooligosaccharide (LOS) to the asialoglycoprotein receptor on the surface of the urethral epithelial cell. This initiates a process of clathrin-dependent receptor mediated endocytosis resulting in the internalization of the gonococcus. Studies in human urethral cells from men are now focusing on the intracellular life of the gonococcus using chip array technology and proteomics to determine changes in bacterial and eukaryotic gene and protein expression as a result of this infection. Studies in women have shown that infection in cervical epithelial cells is initiated by surface ruffling induced by the interaction of the gonococcus with the complement receptor 3 (CR3) receptor on the surface of the epithelial cell. This initiates an actin-dependent process that results in the internalization of gonococci into cervical epithelial cells. Present studies are focusing on the ligand on the surface of the gonococcus that binds to CR3 and the cervical cell signaling process, which ensues. Recent studies in the Apicella Lab indicate that the gonococcus can form a biofilm during infection in patients. Studies are now underway defining the nature of this structure at the biochemical and genetic level.
The studies of the Apicella laboratory on nontypeable Haemophilus influenzae (NTHi) have shown that NTHi invades host cells by binding of the platelet-activating factor (PAF) receptor via LOS glycoforms containing phosphorylcholine (ChoP). The binding of the PAF receptor by NTHi initiates receptor coupling to a pertussis toxin-sensitive heterotrimeric G protein complex, resulting in a multifactorial host cell signal cascade and bacterial invasion. We are currently engaged in studies of NTHi biofilm formation in continuous flow chambers and during infection of airway epithelial cells. To date, these studies suggest that sialic acid plays an important role in biofilm development and gene regulation within the NTHi biofilm.
Recent publications
Apicella, MA, Post, DMB, Fowler, CA, Jones, BD, Rasmussen, JA, Hunt, JR, Imagawa, S, Choudhury, B, Inzana, TJ, Maier, TM, Frank, DW, Zahrt, TC, Jennings, MP, McLendon, MK, and Gibson, BW. Identification, Characterization and Immunogenicity of an O-Antigen Capsular Polysaccharide of Francisella tularensis. PLoS One, Accepted pending revisions.
Johansen, EB, Szoka, FC, Zaleski, A, Apicella, MA, and Gibson, BW. 2010. Utilizing the O-antigen Lipopolysaccharide Biosynthesis Pathway in Escherichia coli to Interrogate the Substrate Specificities of Exogenous Glycosyltransferase Genes in a Combinatorial Approach. Glycobiology 2010 Mar 5. [Epub ahead of print] PMID: 20208062
Wu, HJ, Seib, KL, Srikhanta, YN, Edwards, J, Kidd, SP, Maguire, TL, Hamilton, A, Pan, KT, Hsiao, HH, Yao, CW, Grimmond, SM, Apicella, MA, McEwan, AG, Wang, AH, and Jennings, MP. 2010. Manganese regulation of virulence factors and oxidative stress resistance in Neisseria gonorrhoeae. Journal of Proteomics 2009 Dec 11. [Epub ahead of print], In Press 2010. PMID: 20004262
Falsetta, ML, Bair, TB, Shan, CK, vanden Hoven, RN, Steichen, CT, McEwan, AG, Jennings, MP, and Apicella, MA. 2009. Transcriptional profiling identifies the metabolic phenotype of gonococcal biofilm. Infection and Immunity 77(9):3522-3532. PMID: 19528210
Neil, RB, and Apicella, MA. 2009. Role of HrpA in biofilm formation of Neisseria meningitidis and regulation of the hrpBAS transcripts. Infection and Immunity 77:2285-2293. PMID: 19289515; PMCID: PMC2687342
Srikhanta, YN, Dowideit, SJ, Edwards, JL, Falsetta, ML, Wu, H-J, Harrison, OB, Fox, KL, Seib, KL, Maguire, TL, Wang, AH-J, Maiden, MC, Grimmond, SM, Apicella, MA, and Jennings, MP. 2009. Phasevarions mediate random switching of gene expression in pathogenic Neisseria. PLoS Pathogens 5(4):e1000400, April 2009. PMID: 19390608; PMCID: PMC2667262
Apicella, MA. 2009. Bacterial otitis media, the chinchilla middle ear, and biofilms. Invited Editorial Commentary. Journal of Infectious Diseases. 199:774-775. PMID: 19183065
Neil, RB, Shao, JQ, and Apicella, MA. 2009. Biofilm formation on human airway epithelia by encapsulated Neisseria meningitidis serogroup B. Microbes and Infection 11(2):281-287. PMID: 19114123
Steichen, CT, Shao, JQ, Ketterer, MR, and Apicella, MA. 2008. Gonococcal cervicitis: a role for biofilm in pathogenesis. Journal of Infectious Diseases 198(12):1856-1861. PMID: 18973432
Apicella, MA. 2008. Isolation and characterization of lipopolysaccharides. Methods in Molecular Biology 431:3-13. PMID: 18287743