The emergence and increasing occurrence of bacterial strains that are resistant to all classes of available antibiotics is a global problem. Current antimicrobials target a relatively small number of essential gene functions including: inhibition of cell wall biosynthesis, and synthesis of macromolecules (proteins, DNA and RNA). Treatment of infections caused by antibiotic resistant bacteria requires new approaches and agents with novel modes of action. The bacterial extracellular proteome (cell envelope, membrane vesicles and secreted proteins) plays a fundamental role in establishing infection by enabling the microbes to adhere to and invade host cells, facilitating nutrient acquisition, host tissue destruction, and suppression of host immune responses. Hence the components of the extracellular proteome are promising targets for drugs/vaccines aimed at preventing bacterial infections. The long-term goal of our research is to enhance our understanding of the phenotypic plasticity of the bacterial extracellular proteome and utilize this information to identify attractive targets for development of new therapeutic interventions. Currently, our research focuses on the role of bacterial extracellular proteomes in colonization and circumvention or exploitation of host immune response using two model organisms Vibrio cholerae and Neisseria gonorrhoeae. We examine these issues using comprehensive proteomic studies, chemical genomics, and state of the art genetic, molecular and biochemical methods.
Zielke RA, Simmons RS, Park BR, Nonogaki M, Emerson S, Sikora AE*. The type II secretion pathway in Vibrio cholerae is characterized by growth-phase dependent expression of exoprotein genes and is positively regulated by sigmaE. Infection and Immunity. 2014 April 14http://iai.asm.org/content/early/2014/04/08/IAI.01292-13.abstract
Zielke RA, Wierzbicki IH, Weber JV, Gafken PR, Sikora AE*. Quantitative proteomics of the Neisseria gonorrhoeae cell envelope and membrane vesicles for the discovery of potential therapeutic targets. Mol. and Cell. Proteom. Epub 2014 March 8.http://www.mcponline.org/content/early/2014/03/08/mcp.M113.029538.abstract
Tran N, Zielke RA, Vining OB, Azevedo MD, Armstrong DJ, Banowetz GM, McPhail KL, Sikora AE*. Development of a Quantitative Assay Amenable for High-Throughput Screening to Target the Type II Secretion System for New Treatments against Plant-Pathogenic Bacteria. J. Biomol. Screen. 2013 Sep;18(8):921-9doi: 10.1177/1087057113485426. Epub 2013 Apr 11.
Sikora, A.E., Zielke, R., Lawrence, D. A., Andrews, P. C., Sandkvist M. (2011). A comprehensive proteomic analysis of Vibrio cholerae type II secretome reveals new proteins including three related serine proteases. Journal of Biological Chemistry, 2011 May 13; 286(19):16555-66.