Genetic Basis of Intestinal Persistence of Salmonella enterica
Salmonella is a leading cause of food borne illness, causing an estimated 1.4 million cases per year in the United States. Serovar Typhimurium is responsible for about 26% of these cases (CDC, 1998). The vast majority of Salmonella infections in mammals and birds are the result of infection with S. enterica subspecies I serovars, yet very few genetic factors that are necessary for intestinal persistence in these reservoirs have been described. Intestinal persistence is critical for shedding and transmission of serovar Typhimurium in mammals and birds, yet this phenomenon and interaction of the organism with the host immune system during persistent infection is poorly understood. The long-term goal of our work is to understand the genetic basis of persistence and host range restriction of Salmonella enterica serovar Typhimurium in its mammalian hosts. We are currently working on the following projects:
1. Functional Genomics of Salmonellae: Generation of a Complete Deletion Library
We are generating a library of targeted deletions using λ red recombination in all non-essential genes of Salmonella enterica serotype Typhimurium ATCC14028 in collaboration with Michael McClelland (Sidney Kimmel Cancer Center, San Diego CA). We currently have generated targeted deletions in 1032 genes specific to Salmonellae, or approximately ¼ of the genome, and are progressing to complete this collection. This library will be used for in vitro and in vivo screening, and will be an outstanding resource for the field!
2. In vitro Screening of Complete Deletion Library.
We are interested in the ability of Salmonellae to perisist in the mammalian and avian intestine, thus we are interested in identification of mutants defective in all aspects of the lifestyle of this important pathogen in the host. We are currently screening our library of deletions to identify mutants with interesting phenotypes in vitro including: motility (both reduced and enhanced), resistance to gastric contents, resistance to bile acids, resistance to NO, biofilm formation, and resistance to antimicrobial peptides. We welcome collaborators on these projects!!
3. In vivo Screening of Complete Deletion Library.
We are currently screening our pooled library in various animals to identify new genes important for intestinal persistence in these models. Animal models we are using are Salmonella-sensitive BALB/c mice, Salmonella-resistant CBA/J mice and Chickens. We are actively pursuing collaborations for large animal livestock models as well, as livestock animals are the primary reservoir of Non-Typhoidal salmonellosis for humans and are thus an important food safety concern. We welcome collaborators on these projects!
Postdoctoral Research Associates
Bogomolnaya, L.M., Aldrich, L., Ragoza, Y., Talamantes, M., McClelland, M., and H. Andrews-Polymenis. (2014) Identification of novel factors involved in modulating motility of Salmonella enterica serotype Typhimurium. PLOS One, Accepted October 7, 2014
Porwollik, S., Santiviago, C.A., Cheng, P. Long, F., Desai, P., Fredlund, J., Srikumar, S., Chu, W., Chen, X., Canals, R., Reynolds, M.M., Bogomolnaya, L., Shields, C. Cui, P., Guo, J., Endicott-Yazdani, T., Yang, H.J., Maple, A., Ragoza, Y., Blondel, C.J., Valenquela, C., Santiviago, C.A., and H. Andrews-Polymenis*, and M. McClelland* (2014) Defined single-gene and multi-gene mutant collections in Salmonella enterica sv. Typhimurium. PLOS One, in press.*Co-corresponding authors
Pezoa, D., Blondel, C.J., Silva, C.A., Yang, H.J., Andrews-Polymenis, H.L., Santiviago, C.A., and I. Contreras. (2014) Only one of the two Type VI secretion systems encoded in the Salmonella enterica serotype Dublin genome is involved in colonization of the avian and murine host. Veterinary Research Journal. 45:2. doi:10.1186/1297-9716-45-22
Bogomolnaya, L.M., Andrews, K.D., Talamantes, M., Maple, A., Ragoza, Y., Vazquez-Torres, A., and H.L. Andrews-Polymenis (2013) The ABC-type efflux pump MacAB protects Salmonella enterica serovar Typhimurium from Oxidative Stress. mBio. 4(5):e00630-13. doi:10.1128/mBio.00630-13.
Elfenbein, J.R., Endicott-Yazdani, T., Porwollik, S. Bogomolnaya, L.M., Cheng, P. Guo, J., Zheng, Y., Yang, H.J., Talamantes, M., Shields, C., Maple, A., Ragoza, Y., DeAtley, K., Tatsch, T., Cui, P., Andrews, K.D., McClelland, M., Lawhon, S., and H. Andrews-Polymenis (2013) Novel determinants of intestinal colonization of Salmonella enterica serotype Typhimurium identified in bovine enteric infection. Infection and Immunity. , doi:10.1128/IAI.00874-13.
Nagy, T.A., Moreland, S.M., Andrews-Polymenis, H.L., and C. Detweiler (2013) The ferric enterobactin transporter, Fep, is required for persistent Salmonella infection. Infection and Immunity. 19 August 2013, doi:10.1128/IAI.00412-13.
Zheng, Y., Sambou, T., Cirillo, J.D., McClelland, M., and H. Andrews-Polymenis (2013) The EAL-domain containing protein STM2215 (rtn) is a cyclic di-GMP phosphodiesterase that is needed during Salmonella infection. Mol. Microbiology. Online 12 July 2013. DOI: 10.1111/mmi.12284.
Pezoa, D., Blondel, C.J., Santiviago, C.A., Andrews-Polymenis, H.L., and I. Contreras (2013) The type VI secretion system encoded in SPI-6 plays a role in gastrointestinal colonization and systemic spread of Salmonella enterica serovar Typhimurium in the chicken. PLoS One 8(5) e63917. PMCID: PMC3653874.
Kullas, A.L., McClelland, M., Yang, H.J., Torres, A., Porwollik, S., Mena, P., Andrews-Polymenis, H., and A.W.M., van der Velden (2011) Salmonella utilize L-asparaginase II to inhibit the response of mammalian T cells. Cell, Host, and Microbe. 12(6), 791-8. doi 10.1016/j.chrom.2012.10.018.
Hao, L.y., Willis, D.K., Andrews-Polymenis, H.L., McClelland, M., and J.D. Barak (2012) Salmonella enterica requires siderophore biosynthesis to colonize plants. App. Environ. Microbiology. 13: 4561-4570.
Canals, R., Xia, X.Q., Fronick, C., Clifton, S.W., Ahmer, B.M.M., Andrews-Polymenis, H.L., Porwollik, S., and M. McClelland (2012) High-throughput comparison of gene fitness among related bacteria. BMC Genomics, 13(1) 212.
Silva, C.A., Blondel, C.J., Quezada, C.P., Porwollik, S., Andrews-Polymenis, H.L., Toro, C.S., Zaldivar, M., Contreras, I., McClelland, M., and C.A. Santiviago (2012) Infection of mice by Salmonella enterica serovar Enteritidis involves additional genes that are absent in the genome of serovar Typhimurium. Infection and Immunity, doi:10.1128/IAI.05497-11.
Kanluk, N.A., Canadlen, V., Bagshaw, R.D., Makowski, M., Braun, V., Landekic, M., Mitra, S., Huang, J., Heo, W.D., Meyer, T., Pelletier, L., Andrews-Polymenis, H., McClelland, M., Pawson, T., Grinstein, S., and J.H. Brumell. (2011) Salmonella exploits Arl8B-directed kinesin activity to promote endosome tubulation and cell-to-cell transfer. Cellular Microbiology. doi:10.1111/j.1462-5822.2011.01663.x
Reynolds, M., Bogomolnaya, L., Guo, J., Aldrich, L., Bokhari, D., Santiviago, C.A., McClelland, M., and H. Andrews-Polymenis (2011) Abrogation of the twin arginine transport system in Salmonella enterica serovar Typhimurium leads to colonization defects during infection. PLoS One. Jan 26;6(1):e15800. PMID 21298091. PMCID: PMC3027627
Weatherspoon, N. Zhao, G., Kong, W., Kong, Y. Morigen, M. Andrews-Polymenis, H., McClelland, M. and Yixin Shi (2011) The CpxR/CpxA two-component system up regulates two Tat-dependent peptidoglycan amidases to confer bacterial resistance to the antimicrobial peptide protamine. Journal of Biological Chemistry. 286(7): 5529-39. PMID:21149452
Winter, S.E., Winter, M. G., Godinez, I. Yang, H.J., Russman, H., Andrews-Polymenis, H.L., and A.J. Baumler (2010) A rapid change in virulence gene expression during the transition from the intestinal lumen into tissue promotes systemic dissemination of Salmonella. PLoS Pathogens 6(8) e1001060.
Blondel, C.J. , Yang, H.J., Castro, B., Chiang, S., Toro, C.S., Zaldívar, M., Contreras, Andrews-Polymenis, H.L.**, and C.A. Santiviago (2010) Contribution of the Type VI Secretion System Encoded in SPI-19 to Chicken Colonization by Salmonella enterica Serotypes Gallinarum and Enteritidis. PLoS ONE 5(7): e11724. doi:10.1371, **Co-corresponding for animal studies.
Reynolds, M.M., Canals, R. McClelland, M., and H.L. Andrews-Polymenis (2011) High-Throughput Screening to Determine the Genetic Requirements for Salmonella Survival under different Growth Conditions. In ‘ Salmonella- from genome to function’ Ed. Steffen Porwollik (Horizon Press) In press.
Canals, R., McClelland, M., Santiviago, C.A., and H.L. Andrews-Polymenis (2010) Genomics of Salmonella ssp. In ‘Genomics of Foodborne Pathogens’. Ed. Wei Zhang & Martin Wiedmann, (Springer) In Press
Andrews-Polymenis, H.L., Baumler, A.J., McCormick, B.A., and F. Fang (2010) Taming the Elephant: Frontiers in Salmonella Biology, Pathogenesis and Prevention. Infection and Immunity. In Press.
Santiviago, C.A., Blondel, C.L., Quezada, C.P., Silva, C.A., Tobar, P.M., Porwollik, S., McClelland, M., Andrews-Polymenis, H.L., Toro, C.S., Zaldivar, M., and I. Contreras (2010) Spontaneous excision of the Salmonella enterica serovar Enteritidis-specific defective prophage-like element ΦSE14. J. Bacteriology, 192(8), 2246-2254.
Nunes, J.S., Lawhon, S.D., Rossetti, C.A., Khare, S., Figueiredo, J.F., Gull, T., Burghardt, R.C., Baumler, A.J., Tsolis, R.M., Andrews-Polymenis, H.L., and L.G. Adams (2010) Morphologic and Cytokine Profile Characterization of Salmonella enterica serovar Typhimurium Infection in Calves with Bovine Leukocyte Adhesion Deficiency. Veterinary Pathology. January 2010 Issue.
Santiviago, C.*, Reynolds, M*. Porwollik, S., Choi, S.H., Long, F., Andrews-Polymenis, H.**, and M. McClelland** (2009) Analysis of pools of targeted Salmonella deletion mutants identifies novel genes affecting fitness during competitive infection in mice. PLOS Pathogens,5(7): e1000477 . *Co-First, **Co-Corresponding
Andrews-Polymenis, H.L.*, Santiviago, C. and M. McClelland* (2009) Novel Genetic Tools for Studying Food Borne Salmonella. Current Opinion in Biotechnology, 20, 1-9.
Katribe, E.L., Bogomolnaya, L.M., and H.L. Andrews-Polymenis (2009) Subspecies IIIa and IIIb Salmonellae are Defective for Colonization of Murine Models of Salmonellosis as Compared to Ssp. I Serotype Typhimurium. J. Bacteriology 191 (8) 2843-2850.
Bogomolnaya, L.M. , Santiviago, C.A. , Yang, H,J., Baumler, A.J., and H.L. Andrews-Polymenis (2008) Form Variation’ of the O12 Antigen is Critical for Persistence of Salmonella Typhimurium in the Murine Intestine. Molecular Microbiology, 70(5), 1105-1119.
Sivula, C.P., Bogomolnaya, L.M., and H.L. Andrews-Polymenis (2008) A Comparison of Cecal Colonization of Salmonella enterica serotype Typhimurium in White Leghorn Chicks and Salmonella-resistant Mice. BMC Microbiology 8, 182.
Lenz, L.L. and H. Andrews-Polymenis. (2008) Silencing the Alarm: insights into the interaction between host and pathogen. EMBO Reports 9, 27-32.
Andrews-Polymenis, H.L., Dorsey, C.,W., Raffatellu, M., and Bäumler. A.J. (2006) ‘Expression, function, and in vivo identification of Salmonella virulence factors.’ In Salmonella Infections: Clinical, Immunological and Molecular Aspects. Ed. Pietro Mastroeni (Cambridge University Press).
Andrews-Polymenis, H.L. and Baumler, A.J. ‘Salmonella ssp.’ In Pathogenomics. Ed. Joerg Hacker and Ulrich Dobrindt, (WILEY-VCH Verlag GmbH, Weinheim) 2005.
Tukel, C., Raffatellu, M., Humphries, A.D., Wilson, R.P., Andrews-Polymenis, H.L., Adams, L.G., and Baumler, A.J., (2005) Thin curled fimbriae are a pathogen-associated molecular pattern of Salmonella enterica serotype Typhimurium that is recognized by Toll-like receptor 2. Molecular Microbiology, 58(1), 289-304.
Raffatellu, M., Wilson, R.P., Tran, Q.T., Chessa, D., Andrews-Polymenis, H.L., Lawhon, S.D., Figueiredo, J.F., Adams, L.G., and Baumler, A.J. (2005) Host restriction of Salmonella enterica serotype Typhi is not caused by functional alteration of SipA, SopB or SopD. Infection and Immunity, 73(12), 7817-7826.
Raffatellu, M., Wilson, R.P., Chessa, D., Andrews-Polymenis, H.L., Tran, Q.T., Lawhon, S., Khare, S. Adams, L.G., and Bäumler, A.J. (2005) SipA, SopA, SopB, SopD, and SopE2 contribute to Salmonella enterica serotype Typhimurium invasion of epithelial cells. Infection and Immunity 73(1): 1-9.
Andrews-Polymenis, H.L., Rabsch, W., Porwollik, S., McClelland, M., Rosetti, C., Adams, L.G., and Bäumler, A.J.(2004) Host restriction of Salmonella enterica serotype Typhimurium pigeon isolates does not correlate with loss of discrete genes. Journal of Bacteriology 186(9): 2619-2628.
Zhang, S., Kingsley, R.A., Santos, R.L., Andrews-Polymenis, H., Raffatellu, M., Figueiredo, J., Nunes, J., Tsolis, R.M., Adams, L.G., and Bäumler, A.J. (2003) Molecular Pathogenesis of Salmonella enterica serotype Typhimurium-Induced Diarrhea. Infection and Immunity 71(1): 1-12.
Rabsch, W., Andrews, H.L., Kingsley, R.A., Prager, R., Tschaepe, H., Adams, L.G., and A. Bäumler, (2002) Salmonella enterica serotype Typhimurium and its host adapted variants. Infection and Immunity 70: 2249-2255.
Watarai, M.*, Andrews, H.L.*, and Isberg, R. R., (2001) Formation of a fibrous structure on the surface of Legionella pneumophila associated with exposure of DotH and DotO proteins after intracellular growth. Molecular Microbiology 39(2): 313-329. *The first two authors contributed equally to this work.
Vogel, J.P., Andrews, H.L., Wong, S.K., and Isberg, R.R. (1998) Conjugative transfer by the virulence system of Legionella pneumophila. Science 279: 873-876.
Andrews, H.L., Vogel, J.P., and Isberg, R.R. (1998) Identification of linked genes of Legionella pneumophila essential for intracellular growth and evasion of the endocytic pathway. Infection and Immunity 66(3): 950-958.
Kirby, J.E., Vogel, J.P., Andrews, H.L., and Isberg, R.R. (1998) Evidence for pore forming ability by L. pneumophila. Molecular Microbiology 27(2): 323-336.
Wang, J., Andrews, H., and Thukral, V., (1992) Presynaptic glutamate receptors regulate noradrenaline release from isolated nerve terminals. J. Neurochemistry 58(1): 204-211.