*Not accepting graduate student applications
The major focus of research in my laboratory is centered on bacterial pathogenesis of Yersinia enterocolitica
and Y. pestis
, etiologic agents of yersiniosis and bubonic plague respectively. The hallmark of these infectious agents is their ability to suppress the innate immune response of mammalian hosts. This is accomplished actively by injecting protein anti-host factors directly into white blood cells to circumvent cytokine induction, and passively by repressing or modifying bacterial surface components recognized by toll-like receptors (TLRs). Deacylation of lipidA reduces activation of TLR-4. Transcriptional arrest (Y. enterocolitica) or permanent mutational silencing of flagellin (Y. pestis
) circumvents activation of host cell TLR-5. Flagellin, the major filament protein of the bacterial flagellin is exported to the cell surface via a type III protein secretion system (TTSS), the same type of export mechanism used to deliver virulence proteins to macrophages. We have shown that flagellin, if artificially expressed under host conditions, is actively secreted by virulence TTSS, so repression of this protein may be essential in evasion of innate immunity. We are actively testing this hypothesis. We have also shown that exposure of immunologically naïve mice to synthetic lipid A compounds that induce TLR-4 mediated cytokine responses, are protective when mice are challenged with lethal doses of Y. pestis
. Furthermore, these lipid A mimetics have powerful adjuvant properties and their use with two Y. pestis
protective antigens has a powerful potential as a protective vaccine. Our goal is to adapt these observations for novel protective measures and vaccine strategies.
- Dustin J. Van Hofwegen, Carolyn J. Hovde, and Scott A. Minnich. 2015. Rapid evolution of citrate utilization by Escherichia coli K12 by direct selection requires citT and dctA. J. of Bacteriol. (provisionally accepted pending additional experiment)
- Haiqing Sheng, Smriti Shringi, Katherine N. K. Baker, Scott A. Minnich, Carolyn J. Hovde, Thomas E. Besser. 2015. Standardized Escherichia coli O157:H7 Exposure studies in cattle provide evidence that bovine factors do not drive increased summertime colonization. Appl. Environ. Micobiol. (in press).
- Kolodziejek AM, Caplan AB, Bohach GA, Paszczynski AJ, Minnich SA, Hovde CJ. 2013.
- Seo K. S., J. W. Kim, J. Y. Park, A. K. Viall, S.S. Minnich, H. N. Rohde, D. R. Schnider, S. Y. Lim, J. B. Hong, B. J. Hinnebusch, J. L. O’Loughlin, G. A. Bohach, C. J. Hovde, S. A. Minnich. 2012. The role of intimin/invasin-like protein (Ilp) in Yersinia pestis virulence. Infect. Immun. 80(10):3559-69.
- Kolodziejek A. M., C.J. Hovde, S.A. Minnich. 2012. Yersinia pestis Ail: multiple roles of a single protein. Frontiers Cell Infect. Microbiol. 2:1-10.
- Sheng, H H, J Wang, JY Lim, C Davitt, and SA Minnich, CJ Hovde. 2011. Internalization of Escherichia coli O157:H7 by bovine rectal epithelial cells. Frontiers Microbiol. 2:32.doi:10.3389/fmicb.2011.00032. PMCID 3109292
- Kolodziejek, A. M., Schnider, D. R., Rohde, N.H., Wojtowicz, A. J., Bohach, G. A., Minnich, S.A., and Hovde, C. J. (2010). Outer membrane protein X (Ail) contributes to Yersinia pestis virulence in pneumonic plague and its activity is dependent on the lipopolysaccharide core length. Infect Immun. 78:5233-5243.
- Spinner, J.L., Seo, K.S., O’Loughlin, J.L., Cundiff, J.A., Minnich, S. A., Bohach, G.A., and Kobayashi, S. D. (2010). Neutrophils are resistant to Yersinia YopJ/P-induced apoptosis and are protected from ROS-mediated cell death by the type III secretion system. PLoS One. 5:e9279.
- O’Loughlin, J.L., Spinner, J.L, Minnich, S. A., and Kobayashi, S. D. (2010). Yersinia pestis two-component systems protmote survival in human neutrophils. Infect Immun. 78:773-782.
- Larson, C.L. Christensen, J.E., Pacheco, S.A., Minnich, S.A., and M.E. Konkel (2008) Campylobacter jejuni secretes proteins via the flagellar type III secretion system that contribute to host cell invasion and gastroenteritis. In: Campylobacter 3rd Ed. Eds. Nachamkin et al., ASM Press, Washington, DC
- Airhart, C. L., H. N. Rohde, G. A. Bohach, C. J. Hovde, C. F. Deobald, S. S. Lee & S. A. Minnich, (2008a) Induction of innate immunity by lipid A mimetics increases survival from pneumonic plague. Microbiology 154: 2131-2138.
- Airhart, C. L., H. N. Rohde, C. J. Hovde, G. A. Bohach, C. F. Deobald, S. S. Lee & S. A. Minnich, (2008b) Lipid A mimetics are potent adjuvants for an intranasal pneumonic plague vaccine. Vaccine 26: 5554-5561.
- Sheng, H., J. Y. Lim, M. K. Watkins, S. A. Minnich & C. J. Hovde, (2008) Characterization of an Escherichia coli O157:H7 O-antigen deletion mutant and effect of the deletion on bacterial persistence in the mouse intestine and colonization at the bovine terminal rectal mucosa. Appl Environ Microbiol 74: 5015-5022.
- Kolodziejek, A. M., D. J. Sinclair, K. S. Seo, D. R. Schnider, C. F. Deobald, H. N. Rohde, A. K. Viall, S. S. Minnich, C. J. Hovde, S. A. Minnich & G. A. Bohach, (2007) Phenotypic characterization of OmpX, an Ail homologue of Yersinia pestis KIM. Microbiology 153: 2941-2951.
- Minnich, S. A. & H. N. Rohde, (2007) A rationale for repression and/or loss of motility by pathogenic Yersinia in the mammalian host. Adv Exp Med Biol 603: 298-310.
- Dobbin, H. S., C. J. Hovde, C. J. Williams & S. A. Minnich, (2006) The Escherichia coli O157 flagellar regulatory gene flhC and not the flagellin gene fliC impacts colonization of cattle. Infect Immun 74: 2894-2905.
- V. Kapatral , J. W. Campbell, S. A. Minnich, N. R. Thomson, P. Matsumura and B. M. Pruess. 2004. Gene array analysis of Yersinia enterocolitica FlhD and FlhC: regulation of enzymes affecting synthesis and degradation of carbamoylphosphate. Microbiology 150: p. 2289-2300.
- Monday S.R., Minnich S.A., Feng PC. 2004. A 12-base-pair deletion in the flagellar master control gene flhC causes nonmotility of the pathogenic German sorbitol-fermenting Escherichia coli O157:H-strains. J Bacteriol. 186:2319-2327.
- Yoon J.W., Minnich S.A., Ahn J.S., Park Y.H., Paszczynski A., Hovde C.J. 2004. Thermoregulation of the Escherichia coli O157:H7 pO157 ecf operon and lipid A myristoyl transferase activity involves intrinsically curved DNA. Mol. Microbiol. 51:419-435.
- Ely B., Ely T.W, Crymes W.B. Jr, Minnich S.A. 2000. A family of six flagellin genes contributes to the Caulobacter crescentus flagellar filament. J. Bacteriol. 182:5001-5004.
- Rohde J.R., Luan X.S., Rohde H., Fox J.M., Minnich S.A. 1999. The Yersinia enterocolitica pYV virulence plasmid contains multiple intrinsic DNA bends which melt at 37 degrees C. J Bacteriol 181:4198-4204.