Patrick Eichenberger

Bacillus subtilis is a non-pathogenic soil bacterium and the prevalent model organism for all low GC Gram-positive bacteria. When B. subtilis cells are starved, they initiate a developmental program that culminates in the formation of highly resistant endospores (also referred to as spores). Endospore formation (sporulation) constitutes a relatively simple developmental system in which the generation of distinct cell types can be investigated experimentally. In previous work in the laboratory of Prof. Richard Losick at Harvard University, we have used a variety of genomics techniques to identify most, if not all, of the genes that are specifically turned on during the process of sporulation in B. subtilis. However, the function of many of these newly-identified genes remains undetermined.

1. B. subtilis spore coat composition and assembly during sporulation

In my laboratory, our characterization of newly-identified sporulation genes focuses on genes involved in the formation of the outermost structure of the mature spore: the spore coat. The coat is a proteinaceous shell surrounding the spore. It confers resistance to various chemicals and is required to maintain the structural integrity of the spore to avoid spontaneous spore germination. More than 30 different coat proteins had been previously characterized in B. subtilis from classical genetic screens. In order to identify the complete repertoire of genes encoding coat proteins, we have performed a systematic program of gfp fusions to the sporulation genes that were identified in our transcriptional profiling experiments. The subcellular localization of all of the resulting protein fusions was investigated and as a result, 24 novel coat proteins have been identified. These fusions localize as rings or polar caps around the maturing forespore. We are also expressing all of the newly-generated fusions in cells mutant for genes involved in spore coat assembly. In parallel, we have observed by time-course microscopy that several of the novel coat proteins display dynamic patterns of spore coat localization. We would like to determine how these proteins affect subcellular localization of other coat proteins. The ultimate goal is to obtain a detailed assembly map of the entire developing spore coat.

2. Comparative genomics analysis of sporulation in endospore-forming bacteria

Many genome sequences of bacteria related to B. subtilis (from the genera Bacillus and Clostridium) have been released recently. We are interested in performing a comparative genomics analysis of sporulation in several endospore-forming species. Using bioinformatics, we can identify orthologs of all known sporulation genes in all of the sequenced genomes and estimate the minimal set of conserved sporulation genes. We will also seek to identify species-specific sporulation genes, i.e. genes absent in B. subtilis but expressed in other endospore-forming bacteria, especially in the non-pathogenic Sterne strain of B. anthracis. Sporulation transcription factors (and their DNA binding domains) are usually conserved in other endospore-formers, although their target genes can differ. Therefore, in species related to Bacillus subtilis, binding sites for sporulation transcription factors can be searched in the upstream sequence of genes of unknown function using the consensus binding sequences defined in B. subtilis. In parallel, we will perform transcriptional profiling analyses of gene expression during sporulation using B. anthracis DNA microarrays. Each newly-identified B. anthracis-specific sporulation gene will be analyzed in more detail. It is expected that many of these genes will encode coat proteins, because the surface of the spore is likely to have adapted depending on the ecological habitat in which a particular species is found.

Figure 1
Field of sporulating B. subtilis cells of a strain triply mutant for spoIID, spoIIM and spoIIP. The membranes were stained with FM4-64 (red) and the DNA was stained with DAPI (blue). Photo by Patrick Eichenberger. For details, see Eichenberger et al. (2001).

Figure 2
Field of sporulating B. subtilis cells producing GFP (green) fused in-frame to the C terminus of CotT, a spore coat protein. Photo by Paul Grabowski. For details, see Kim et al. (2006).

Microbiology and Microbial Genomics (V23.0044)

I also give lectures in Principles of Biology (V23.0014), Biocore (G23.1001) and Developmental Genetics (G16.2610).

After studying Biochemistry and Molecular Biology, I obtained my Ph.D. from the University of Geneva in 1997. My doctoral work in the laboratory of Prof. Hans Geiselmann focused on the analysis of mechanisms of transcriptional activation in the bacterium Escherichia coli. Then, as a post-doctoral fellow, I moved to the laboratory of Prof. Richard Losick at Harvard, where I spent six wonderful years investigating various aspects of sporulation in Bacillus subtilis with a special emphasis on genome-wide identification of sporulation genes. I joined NYU Biology’s department as an Assistant Professor in October 2004.

Date of these PubMed search results: March 24 2020
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1. Compatibility of Site-Specific Recombination Units between Mobile Genetic Elements.
   iScience (2020 Jan 24) PMC6957869 free full-text archive
   Suzuki S, Yoshikawa M, Imamura D, Abe K, Eichenberger P, Sato T
2. Expansion of the Spore Surface Polysaccharide Layer in Bacillus subtilis by Deletion of Genes Encoding Glycosyltransferases and Glucose Modification Enzymes.
   J Bacteriol (2019 Oct 1) PMC6755746 free full-text archive
   Shuster B, Khemmani M, Nakaya Y, Holland G, Iwamoto K, Abe K, Imamura D, Maryn N, Driks A, Sato T, Eichenberger P
3. Bacillus subtilis Spore Resistance to Simulated Mars Surface Conditions.
   Front Microbiol (2019) PMC6399134 free full-text archive
   Cortesao M, Fuchs FM, Commichau FM, Eichenberger P, Schuerger AC, Nicholson WL, Setlow P, Moeller R
4. Contributions of crust proteins to spore surface properties in Bacillus subtilis.
   Mol Microbiol (2019 Mar) PMC6417949 free full-text archive
   Shuster B, Khemmani M, Abe K, Huang X, Nakaya Y, Maryn N, Buttar S, Gonzalez AN, Driks A, Sato T, Eichenberger P
5. SpoVID functions as a non-competitive hub that connects the modules for assembly of the inner and outer spore coat layers in Bacillus subtilis.
   Mol Microbiol (2018 Nov) PMC6282716 free full-text archive
   Nunes F, Fernandes C, Freitas C, Marini E, Serrano M, Moran CP Jr, Eichenberger P, Henriques AO
6. The Spore Coat.
   Microbiol Spectr (2016 Apr) PMID: 27227299
   Driks A, Eichenberger P
7. An experimentally supported model of the Bacillus subtilis global transcriptional regulatory network.
   Mol Syst Biol (2015 Nov 17) PMC4670728 free full-text archive
   Arrieta‑Ortiz ML, Hafemeister C, Bate AR, Chu T, Greenfield A, Shuster B, Barry SN, Gallitto M, Liu B, Kacmarczyk T, Santoriello F, Chen J, Rodrigues CD, Sato T, Rudner DZ, Driks A, Bonneau R, Eichenberger P
8. Dual-specificity anti-sigma factor reinforces control of cell-type specific gene expression in Bacillus subtilis.
   PLoS Genet (2015 Apr) PMC4383634 free full-text archive
   Serrano M, Gao J, Bota J, Bate AR, Meisner J, Eichenberger P, Moran CP Jr, Henriques AO
9. Developmentally-regulated excision of the SPbeta prophage reconstitutes a gene required for spore envelope maturation in Bacillus subtilis.
   PLoS Genet (2014 Oct) PMC4191935 free full-text archive
   Abe K, Kawano Y, Iwamoto K, Arai K, Maruyama Y, Eichenberger P, Sato T
10. Bacillus subtilis Systems Biology: Applications of -Omics Techniques to the Study of Endospore Formation.
    Microbiol Spectr (2014 Apr) PMID: 26105826
    Bate AR, Bonneau R, Eichenberger P
11. RemA is a DNA-binding protein that activates biofilm matrix gene expression in Bacillus subtilis.
    Mol Microbiol (2013 Jun) PMC3732408 free full-text archive
    Winkelman JT, Bree AC, Bate AR, Eichenberger P, Gourse RL, Kearns DB
12. The Bacillus subtilis endospore: assembly and functions of the multilayered coat.
    Nat Rev Microbiol (2013 Jan) PMID: 23202530
    McKenney PT, Driks A, Eichenberger P
13. Physical interaction between coat morphogenetic proteins SpoVID and CotE is necessary for spore encasement in Bacillus subtilis.
    J Bacteriol (2012 Sep) PMC3430338 free full-text archive
    de Francesco M, Jacobs JZ, Nunes F, Serrano M, McKenney PT, Chua MH, Henriques AO, Eichenberger P
14. SlrA/SinR/SlrR inhibits motility gene expression upstream of a hypersensitive and hysteretic switch at the level of sigma(D) in Bacillus subtilis.
    Mol Microbiol (2012 Mar) PMC3303961 free full-text archive
    Cozy LM, Phillips AM, Calvo RA, Bate AR, Hsueh YH, Bonneau R, Eichenberger P, Kearns DB
15. Dynamics of spore coat morphogenesis in Bacillus subtilis.
    Mol Microbiol (2012 Jan) PMC3256263 free full-text archive
    McKenney PT, Eichenberger P
16. Multi-species integrative biclustering.
    Genome Biol (2010) PMC2965388 free full-text archive
    Waltman P, Kacmarczyk T, Bate AR, Kearns DB, Reiss DJ, Eichenberger P, Bonneau R
17. Hierarchical evolution of the bacterial sporulation network.
    Curr Biol (2010 Sep 14) PMC2944226 free full-text archive
    de Hoon MJ, Eichenberger P, Vitkup D
18. A distance-weighted interaction map reveals a previously uncharacterized layer of the Bacillus subtilis spore coat.
    Curr Biol (2010 May 25) PMC2920530 free full-text archive
    McKenney PT, Driks A, Eskandarian HA, Grabowski P, Guberman J, Wang KH, Gitai Z, Eichenberger P
19. Direct and indirect control of late sporulation genes by GerR of Bacillus subtilis.
    J Bacteriol (2010 Jul) PMC2897654 free full-text archive
    Cangiano G, Mazzone A, Baccigalupi L, Isticato R, Eichenberger P, De Felice M, Ricca E
20. The red-ox status of a penicillin-binding protein is an on/off switch for spore peptidoglycan synthesis in Bacillus subtilis.
    Mol Microbiol (2010 Jan) PMID: 19919674
    Eichenberger P
21. The coat morphogenetic protein SpoVID is necessary for spore encasement in Bacillus subtilis.
    Mol Microbiol (2009 Nov) PMC2806667 free full-text archive
    Wang KH, Isidro AL, Domingues L, Eskandarian HA, McKenney PT, Drew K, Grabowski P, Chua MH, Barry SN, Guan M, Bonneau R, Henriques AO, Eichenberger P
22. The forespore line of gene expression in Bacillus subtilis.
    J Mol Biol (2006 Apr 21) PMID: 16497325
    Wang ST, Setlow B, Conlon EM, Lyon JL, Imamura D, Sato T, Setlow P, Losick R, Eichenberger P
23. The Bacillus subtilis spore coat protein interaction network.
    Mol Microbiol (2006 Jan) PMID: 16390444
    Kim H, Hahn M, Grabowski P, McPherson DC, Otte MM, Wang R, Ferguson CC, Eichenberger P, Driks A
24. Characterization of the Bacillus subtilis spore morphogenetic coat protein CotO.
    J Bacteriol (2005 Dec) PMC1317010 free full-text archive
    McPherson DC, Kim H, Hahn M, Wang R, Grabowski P, Eichenberger P, Driks A
25. Defining a centromere-like element in Bacillus subtilis by Identifying the binding sites for the chromosome-anchoring protein RacA.
    Mol Cell (2005 Mar 18) PMID: 15780934
    Ben‑Yehuda S, Fujita M, Liu XS, Gorbatyuk B, Skoko D, Yan J, Marko JF, Liu JS, Eichenberger P, Rudner DZ, Losick R
26. Unmasking novel sporulation genes in Bacillus subtilis.
    J Bacteriol (2004 Dec) PMC529092 free full-text archive
    Silvaggi JM, Popham DL, Driks A, Eichenberger P, Losick R
27. The program of gene transcription for a single differentiating cell type during sporulation in Bacillus subtilis.
    PLoS Biol (2004 Oct) PMC517825 free full-text archive
    Eichenberger P, Fujita M, Jensen ST, Conlon EM, Rudner DZ, Wang ST, Ferguson C, Haga K, Sato T, Liu JS, Losick R
28. Dynamic patterns of subcellular protein localization during spore coat morphogenesis in Bacillus subtilis.
    J Bacteriol (2004 Jul) PMC438564 free full-text archive
    van Ooij C, Eichenberger P, Losick R
29. A threshold mechanism governing activation of the developmental regulatory protein sigma F in Bacillus subtilis.
    J Biol Chem (2004 Apr 9) PMID: 14744853
    Carniol K, Eichenberger P, Losick R
30. The Spo0A regulon of Bacillus subtilis.
    Mol Microbiol (2003 Dec) PMID: 14651647
    Molle V, Fujita M, Jensen ST, Eichenberger P, Gonzalez‑Pastor JE, Liu JS, Losick R
31. The sigmaE regulon and the identification of additional sporulation genes in Bacillus subtilis.
    J Mol Biol (2003 Apr 11) PMID: 12662922
    Eichenberger P, Jensen ST, Conlon EM, van Ooij C, Silvaggi J, Gonzalez‑Pastor JE, Fujita M, Ben‑Yehuda S, Stragier P, Liu JS, Losick R
32. Identification of a new gene essential for germination of Bacillus subtilis spores with Ca2+-dipicolinate.
    J Bacteriol (2003 Apr) PMC151495 free full-text archive
    Ragkousi K, Eichenberger P, van Ooij C, Setlow P
33. Genome-wide analysis of the stationary-phase sigma factor (sigma-H) regulon of Bacillus subtilis.
    J Bacteriol (2002 Sep) PMC135291 free full-text archive
    Britton RA, Eichenberger P, Gonzalez‑Pastor JE, Fawcett P, Monson R, Losick R, Grossman AD
34. A three-protein inhibitor of polar septation during sporulation in Bacillus subtilis.
    Mol Microbiol (2001 Dec) PMID: 11886548
    Eichenberger P, Fawcett P, Losick R
35. The transcriptional profile of early to middle sporulation in Bacillus subtilis.
    Proc Natl Acad Sci U S A (2000 Jul 5) PMC16670 free full-text archive
    Fawcett P, Eichenberger P, Losick R, Youngman P