- Bacterial pathogenesis
- Bacterial adhesion
- Salmonella and Escherichia coli fimbriae
- Salmonella and adhesin vaccines
- Yersinia pestis and pneumonic plague
Key words: Yersinia pestis, Salmonella, Escherichia coli, fimbriae, adhesion, plague.
Description of Research
The long-term goal of this laboratory is to understand how bacterial pathogens initiate their infectious process. Our research is directed towards bacterial ligands that bind to specific host receptors and mediate bacterial colonization, host cell signaling, and/or optimal toxin delivery. A better understanding of the structure and function of the microbial ligands and host receptors will help to design new prophylactic and therapeutic approaches against bacterial pathogens. Studies in this laboratory are focused on Yersinia pestis, Escherichia coli and Salmonella ligands. Although Yersinia pestis, the causative agent of plague is best known to be transmitted by fleas to cause bubonic plague, it can also be inhaled, triggering the more contagious and lethal pneumonic plague. There is currently no protective vaccine against pneumonic plague and we are studying the structure and function of putative adhesins, as well as their immunogenic and protective properties for the development of a multi-subunit vaccine. Recently, we became interested in the use of next generation sequencing methods to screen for the distribution of virulence factors and virulence factor alleles in large collections of Salmonella isolates. We are looking for associations of specific virulence factor alleles with the strain origins, pathotypes, and the presence of antibiotic resistance genes, antibiotypes. Detected associations are then being studied for biological relevance.
The 987P-like CS18 fimbriae of human enterotoxigenic Escherichia coli ON phase variants. Fimbrial expression is regulated by CS18-specific DNA recombinases catalizing the inversion of a promoter-containing DNA segment. (Molecular Microbiology, Volume 48, Number 1, 2003, cover illustration)
Rotation Projects for 2013-2014
1. Switching virulence factor SNPs between Salmonella strains and functional assays.
2. Studies of new secretion systems of Y. pestis
Min Yue, Ph.D., Postdoctoral Fellow -
Leon de Masi, Ph.D., Postdoctoral Fellow -
Xiangan Han, Ph.D., visiting scholar (Chinese Academy of Agricultural Sciences, Shanghai, China) -
Chunhong Zhu, Ph.D., visiting scholar (Chinese Academy of Agricultural Sciences, Yangzhou, Jiangsu, China)
Zhang Junjie, De Masi Leon, John Beena, Chen Wenxin, Schifferli Dieter M Improved delivery of the OVA-CD4 peptide to T helper cells by polymeric surface display on Salmonella. Microbial cell factories 13: 80, 2014.Yue Min, Schifferli Dieter M Allelic variation in Salmonella: an underappreciated driver of adaptation and virulence. Frontiers in microbiology 4: 419, 2014.Bao, R., Nair, M. K., Tang, W. K., Esser, L., Sadhukhan, A., Holland, R. L., Xia, D., Schifferli, D. M. Structural basis for the specific recognition of dual receptors by the homopolymeric pH 6 antigen (Psa) fimbriae of Yersinia pestis Proc Natl Acad Sci U S A 110: 1065-70, 2013.Bao Rui, Esser Lothar, Sadhukhan Annapurna, Nair Manoj K M, Schifferli Dieter M, Xia Di Crystallization and preliminary X-ray diffraction analysis of PsaA, the adhesive pilin subunit that forms the pH 6 antigen on the surface of Yersinia pestis. Acta crystallographica. Section F, Structural biology and crystallization communications 68: 1243-1246, 2012.Yue Min, Schmieder Robert, Edwards Robert A, Rankin Shelley C, Schifferli Dieter M Microfluidic PCR Combined with Pyrosequencing for Identification of Allelic Variants with Phenotypic Associations among Targeted Salmonella Genes. Applied and environmental microbiology 78: 7480-2, 2012.Bartra Sara Schesser, Gong Xin, Lorica Cherish D, Jain Chaitanya, Nair Manoj K M, Schifferli Dieter, Qian Lianfen, Li Zhongwei, Plano Gregory V, Schesser Kurt The outer membrane protein A (OmpA) of Yersinia pestis promotes intracellular survival and virulence in mice. Microbial pathogenesis 52: 41-6, 2012.Yue Min, Rankin Shelley C, Blanchet Ryan T, Nulton James D, Edwards Robert A, Schifferli Dieter M Diversification of the Salmonella fimbriae: a model of macro- and microevolution. PloS one 7: e38596, 2012.Guo Jitao, Nair Manoj K M, Galván Estela M, Liu Shu-Lin, Schifferli Dieter M Tn5AraOut mutagenesis for the identification of Yersinia pestis genes involved in resistance towards cationic antimicrobial peptides. Microbial pathogenesis 51: 121-32, 2011.Zhu Liqian, Ding Xiuyan, Zhu Xiaofang, Meng Songshu, Wang Jianye, Zhou Hong, Duan Qiangde, Tao Jie, Schifferli Dieter M, Zhu Guoqiang Biphasic activation of PI3K/Akt and MAPK/Erk1/2 signaling pathways in bovine herpesvirus type 1 infection of MDBK cells. Veterinary research 42: 57, 2011.O'Keefe Alexandra, Hutton Tabitha A, Schifferli Dieter M, Rankin Shelley C First detection of CTX-M and SHV extended-spectrum beta-lactamases in Escherichia coli urinary tract isolates from dogs and cats in the United States. Antimicrobial agents and chemotherapy 54: 3489-92, 2010.Galván Estela M, Lasaro Melissa A S, Schifferli Dieter M Capsular antigen fraction 1 and Pla modulate the susceptibility of Yersinia pestis to pulmonary antimicrobial peptides such as cathelicidin. Infection and immunity 76: 1456-64, 2008.Guo Aizhen, Lasaro Melissa A, Sirard Jean-Claude, Kraehenbühl Jean-Pierre, Schifferli Dieter M Adhesin-dependent binding and uptake of Salmonella enterica serovar Typhimurium by dendritic cells. Microbiology (Reading, England) 153: 1059-69, 2007.Galván Estela M, Chen Huaiqing, Schifferli Dieter M The Psa fimbriae of Yersinia pestis interact with phosphatidylcholine on alveolar epithelial cells and pulmonary surfactant. Infection and immunity 75: 1272-9, 2007.Chen Huaiqing, Schifferli Dieter M Comparison of a fimbrial versus an autotransporter display system for viral epitopes on an attenuated Salmonella vaccine vector. Vaccine 25: 1626-33, 2007.Liu, Fengzhi. Chen, Huaiqing. Galvan, Estela M. Lasaro, Melissa A. Schifferli, Dieter M. Effects of Psa and F1 on the adhesive and invasive interactions of Yersinia pestis with human respiratory tract epithelial cells. Infection & Immunity 74: 5636-44, 2006.Zhu, Guoqiang. Chen, Huaiqing. Choi, Byung-Kwon. Del Piero, Fabio. Schifferli, Dieter M. Histone H1 proteins act as receptors for the 987P fimbriae of enterotoxigenic Escherichia coli. Journal of Biological Chemistry 280: 23057-65, 2005.Schifferli, D. M. Adhesins of enterotoxigenic Escherichia coli strains that infect animals EcoSal-Escherichia coli and Salmonella. Cellular and Molecular Biology, ASM Press, Washington, D.C. : , 2005.Guo, A., S. Cao, L. Tu, P. Chen, C. Zhang, A. Jia, W. Yang, Z. Liu, H. Chen, and D.M. Schifferli. FimH alleles direct preferential binding of Salmonella to distinct mammalian cells or to avian cells. Microbiology 155: 1623-33, 2009.Galván, E. M., M. A. Lasaro, and D. M. Schifferli F1 and Pla modulate the susceptibility of Yersinia pestis to pulmonary antimicrobial peptides such as cathelicidin. Infect Immun 76: 1456-1464, 2008.Galván EM, Nair MK, Chen H, Del Piero F, Schifferli DM. Biosafety level 2 model of pneumonic plague and protection studies with F1 and Psa. Infect. Immun. 78: 3443-53, 2010.