Prof. Anat Herskovits

Our lab is focused on understanding the interactions between the human bacterial pathogen Listeria monocytogenes and mammalian cells, specifically, macrophage cells. We explore different strategies of L. monocytogenes that allow it to infect and replicate efficiently within mammalian cells, evade recognition by the innate immune system and manipulate host cellular pathways. We combine computational, biochemical and genetic approaches to decipher these mechanisms. 

Projects in the lab include:

• Studying the interactions of L. monocytogenes with the innate immune system
• Studying the role of MDR transporters in activation of innate immune response and in L. monocytogenes physiology
• Identification of novel effector proteins of L. monocytogenes
• L. monocytogenes metabolism during intracellular growth
• Regulation of virulence genes via metabolic signals
• The role of the Sec system in L. monocytogenes virulence
• • Pathogen-host-phage interactions

Listeria monocytogenes MDR transporters are involved in LTA synthesis and triggering of innate immunity during infection.  Keren Tadmor, Yair Pozniak, Tamar Burg Golani, Lior Lobel, Moran Brenner, Nadejda Sigal, and Anat A. Herskovits. Front Cell Infect Microbiol. 2014; 4: 16.

Membrane Chaperone SecDF Plays a Role in the Secretion of Listeria monocytogenes Major Virulence Factors. Tamar Burg-Golani, Yair Pozniak, Lev Rabinovich, Nadejda Sigal, Ran Nir Paz and Anat A. Herskovits J. Bacteriol. December 2013 vol. 195 no. 23 5262-5272

Listeria monocytogenes MDR transporters and c-di-AMP that contribute to Type I interferons induction, play a role in cell wall stress. Millie Kaplan Zeevi, Nirit S. Shafir, Shira Shaham, Sivan Friedman, Nadejda Sigal, Ran Nir-Paz, Ivo G. Boneca and Anat A. Herskovits J. Bacteriol. December 2013 vol. 195 no. 23 5250-5261
 

Prophage Excision Activates Listeria Competence Genes that Promote Phagosomal Escape and Virulence. Lev Rabinovich, Nadejda Sigal, Ilya Borovok, Ran Nir-Paz, and Anat A. Herskovits Cell 150, 792–802, August 17, 2012

Integrative Genomic Analysis Identifies Isoleucine and CodY as Regulators of Listeria monocytogenes Virulence Lior Lobel, Nadejda Sigal, Ilya Borovok, Eytan Ruppin, and Anat A. Herskovits. PLoS Genet 8(9): e1002887. doi:10.1371/journal.pgen.1002887

Listeria monocytogenes 6-Phosphogluconolactonase mutants induce increased activation of a host cytosolic surveillance pathway. Crimmins GT, Schelle MW, Herskovits AA, Ni PP, Kline BC, Meyer-Morse N, Iavarone AT, Portnoy DA. Infect Immun. 2009 Jul;77(7):3014-22. Epub 2009 Apr 27.

Listeria monocytogenes multidrug resistance transporters activate a cytosolic surveillance pathway of innate immunity. Crimmins GT, Herskovits AA, Rehder K, Sivick KE, Lauer P, Dubensky TW Jr, Portnoy DA. Proc Natl Acad Sci U S A. 2008 Jul 22;105(29):10191-6. Epub 2008 Jul 16.

Bacterial ligands generated in a phagosome are targets of the cytosolic innate immune system. Herskovits AA, Auerbuch V, Portnoy DA. PLoS Pathog. 2007 Mar;3(3):e51.

The Unc93b1 mutation 3d disrupts exogenous antigen presentation and signaling via Toll-like receptors 3, 7 and 9. Tabeta K, Hoebe K, Janssen EM, Du X, Georgel P, Crozat K, Mudd S, Mann N, Sovath S, Goode J, Shamel L, Herskovits AA, Portnoy DA, Cooke M, Tarantino LM, Wiltshire T, Steinberg BE, Grinstein S, Beutler B. Nat Immunol. 2006 Feb;7(2):156-64. Epub 2006 Jan 15.

Killed but metabolically active microbes: a new vaccine paradigm for eliciting effector T-cell responses and protective immunity. Brockstedt DG, Bahjat KS, Giedlin MA, Liu W, Leong M, Luckett W, Gao Y, Schnupf P, Kapadia D, Castro G, Lim JY, Sampson-Johannes A, Herskovits AA, Stassinopoulos A, Bouwer HG, Hearst JE, Portnoy DA, Cook DN, Dubensky TW Jr. Nat Med. 2005 Aug;11(8):853-60. Epub 2005 Jul 24.

Accumulation of endoplasmic membranes and novel membrane-bound ribosome-signal recognition particle receptor complexes in Escherichia coli. Herskovits AA, Shimoni E, Minsky A, Bibi E. J Cell Biol. 2002 Nov 11;159(3):403-10. Epub 2002 Nov 4. PMID: 12417577 [PubMed - indexed for MEDLINE]Free PMC ArticleFree text

Evidence for coupling of membrane targeting and function of the signal recognition particle (SRP) receptor FtsY. Herskovits AA, Seluanov A, Rajsbaum R, ten Hagen-Jongman CM, Henrichs T, Bochkareva ES, Phillips GJ, Probst FJ, Nakae T, Ehrmann M, Luirink J, Bibi E. EMBO Rep. 2001 Nov;2(11):1040-6.

Putative integral membrane SRP receptors. Bibi E, Herskovits AA, Bochkareva ES, Zelazny A. Trends Biochem Sci. 2001 Jan;26(1):15-6.

New prospects in studying the bacterial signal recognition particle pathway. Herskovits AA, Bochkareva ES, Bibi E.
Mol Microbiol. 2000 Dec;38(5):927-39. Review.

Association of Escherichia coli ribosomes with the inner membrane requires the signal recognition particle receptor but is independent of the signal recognition particle. Herskovits AA, Bibi E. Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4621-6